Target Information

Target General Information

Target ID

T25005 (Former ID: TTDR00233)

Target Name

Tyrosine-protein kinase BTK (ATK)

Synonyms

Bruton's tyrosine kinase; Bruton tyrosine kinase; BPK; B-cell progenitor kinase; B cell progenitor kinase; Agammaglobulinemia tyrosine kinase; Agammaglobulinaemia tyrosine kinase; AGMX1

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Gene Name

BTK

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Malignant haematopoietic neoplasm [ICD-11: 2B33]

Mature B-cell lymphoma [ICD-11: 2A85]

Function

Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis. Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling.

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BioChemical Class

Kinase

UniProt ID

BTK_HUMAN

EC Number

EC 2.7.10.2

Sequence

MAAVILESIFLKRSQQKKKTSPLNFKKRLFLLTVHKLSYYEYDFERGRRGSKKGSIDVEK
ITCVETVVPEKNPPPERQIPRRGEESSEMEQISIIERFPYPFQVVYDEGPLYVFSPTEEL
RKRWIHQLKNVIRYNSDLVQKYHPCFWIDGQYLCCSQTAKNAMGCQILENRNGSLKPGSS
HRKTKKPLPPTPEEDQILKKPLPPEPAAAPVSTSELKKVVALYDYMPMNANDLQLRKGDE
YFILEESNLPWWRARDKNGQEGYIPSNYVTEAEDSIEMYEWYSKHMTRSQAEQLLKQEGK
EGGFIVRDSSKAGKYTVSVFAKSTGDPQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELIN
YHQHNSAGLISRLKYPVSQQNKNAPSTAGLGYGSWEIDPKDLTFLKELGTGQFGVVKYGK
WRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG
CLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDF
GLSRYVLDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDIWAFGVLMWEIYSLGKMPYER
FTNSETAEHIAQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLSNILDVMDEES

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T58FWN

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 4 Approved Drugs

Acalabrutinib

Drug Info

Approved

Mantle cell lymphoma

[2]

Ibrutinib

Drug Info

Approved

Mantle cell lymphoma

[3], [4], [5]

Pirtobrutinib

Drug Info

Approved

Non-hodgkin lymphoma

[6]

Zanubrutinib

Drug Info

Approved

Mantle cell lymphoma

[7]

Clinical Trial Drug(s)

[+] 34 Clinical Trial Drugs

GDC-0853

Drug Info

Phase 3

Multiple sclerosis

[8]

ICP-022

Drug Info

Phase 3

Chronic lymphocytic leukaemia

[9]

Tolebrutinib

Drug Info

Phase 3

Multiple sclerosis

[10]

ARQ 531

Drug Info

Phase 2

Hematologic tumour

[11]

BGB-3112

Drug Info

Phase 2

Follicular lymphoma

[12]

BMS-986142

Drug Info

Phase 2

Rheumatoid arthritis

[13]

Branebrutinib

Drug Info

Phase 2

Rheumatoid arthritis

[14]

CC-292

Drug Info

Phase 2

Chronic lymphocytic leukaemia

[15]

DTRM-555

Drug Info

Phase 2

Chronic lymphocytic leukaemia

[16]

GS-4059

Drug Info

Phase 2

B-cell lymphoma

[12]

LOU064

Drug Info

Phase 2

Chronic idiopathic urticaria

[17]

M2951

Drug Info

Phase 2

Multiple sclerosis

[18]

PRN1008

Drug Info

Phase 2

Pemphigus vulgaris

[13], [17]

SAR 444727

Drug Info

Phase 2

Atopic dermatitis

[19]

ACP-319

Drug Info

Phase 1/2

Chronic lymphocytic leukaemia

[20]

CG-806

Drug Info

Phase 1/2

Acute myeloid leukaemia

[21]

Vecabrutinib

Drug Info

Phase 1/2

B-cell lymphoma

[12]

AC0058TA

Drug Info

Phase 1

Autoimmune disease

[13]

BGB-16673

Drug Info

Phase 1

B-cell lymphoma

[22]

BGB-3113

Drug Info

Phase 1

B-cell lymphoma

[12]

BIIB068

Drug Info

Phase 1

Systemic lupus erythematosus

[13]

BIIB091

Drug Info

Phase 1

Multiple sclerosis

[23]

DTRMWXHS-12

Drug Info

Phase 1

B-cell lymphoma

[12]

HM71224

Drug Info

Phase 1

Rheumatoid arthritis

[24]

HMPL-760

Drug Info

Phase 1

Non-hodgkin lymphoma

[25]

JNJ-64264681

Drug Info

Phase 1

Non-hodgkin lymphoma

[26]

M7583

Drug Info

Phase 1

Haematological malignancy

[12]

NX-2127

Drug Info

Phase 1

Non-hodgkin lymphoma

[27]

NX-5948

Drug Info

Phase 1

Non-hodgkin lymphoma

[28]

ONO-4059

Drug Info

Phase 1

B-cell lymphoma

[29]

PRN2246

Drug Info

Phase 1

Multiple sclerosis

[18]

TAK-020

Drug Info

Phase 1

Rheumatoid arthritis

[13]

TG-1701

Drug Info

Phase 1

Non-hodgkin lymphoma

[30]

TT-01488

Drug Info

Phase 1

B-cell non-hodgkin lymphoma

[31]

Patented Agent(s)

[+] 2 Patented Agents

Pyrrolo[2,3-d]pyrimidine derivative 16

Drug Info

Patented

Solid tumour/cancer

[32]

Pyrrolo[2,3-d]pyrimidine derivative 17

Drug Info

Patented

Solid tumour/cancer

[32]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

PCI-45292

Drug Info

Preclinical

Autoimmune diabetes

[33]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

GDC-0834

Drug Info

Terminated

Rheumatoid arthritis

[34]

Mode of Action

[+] 3 Modes of Action

Inhibitor

[+] 70 Inhibitor drugs

Acalabrutinib

Drug Info

[2]

Ibrutinib

Drug Info

[35]

Pirtobrutinib

Drug Info

[36]

Zanubrutinib

Drug Info

[7]

GDC-0853

Drug Info

[13]

ICP-022

Drug Info

[37]

Tolebrutinib

Drug Info

[38]

ARQ 531

Drug Info

[12]

BGB-3112

Drug Info

[12]

BMS-986142

Drug Info

[13]

Branebrutinib

Drug Info

[39]

DTRM-555

Drug Info

[16]

GS-4059

Drug Info

[12], [13]

LOU064

Drug Info

[17]

M2951

Drug Info

[13], [18]

PRN1008

Drug Info

[13], [17]

SAR 444727

Drug Info

[40]

ACP-319

Drug Info

[35]

CG-806

Drug Info

[41]

Vecabrutinib

Drug Info

[12]

AC0058TA

Drug Info

[13]

BGB-3113

Drug Info

[12]

BIIB068

Drug Info

[13]

BIIB091

Drug Info

[42]

DTRMWXHS-12

Drug Info

[43]

HM71224

Drug Info

[44]

HMPL-760

Drug Info

[25]

JNJ-64264681

Drug Info

[45]

M7583

Drug Info

[12]

NX-2127

Drug Info

[46]

NX-5948

Drug Info

[46]

PRN2246

Drug Info

[18]

TAK-020

Drug Info

[13]

TG-1701

Drug Info

[48]

TT-01488

Drug Info

[31]

Imidazopyridine derivative 4

Drug Info

[49]

PMID27774824-Compound-Figure12Example1

Drug Info

[49]

PMID27774824-Compound-Figure12Example10

Drug Info

[49]

PMID27774824-Compound-Figure12Example61

Drug Info

[49]

Pyrazolo[4,3-c]pyridine derivative 2

Drug Info

[49]

Pyrrolo[2,3-d]pyrimidine derivative 12

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 13

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 14

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 15

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 16

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 17

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 18

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 19

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 20

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 21

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 22

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 23

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 25

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 26

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 27

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 28

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 29

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 30

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 31

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 32

Drug Info

[32]

Pyrrolo[2,3-d]pyrimidine derivative 33

Drug Info

[32]

PCI-45292

Drug Info

[50]

GDC-0834

Drug Info

[34]

CGI-1316

Drug Info

[35]

Inositol 1,3,4,5-Tetrakisphosphate

Drug Info

[51]

LFM-A13

Drug Info

[52]

PMID24900538C2c

Drug Info

[53]

PMID24915291C31

Drug Info

[54]

PMID24915291C38

Drug Info

[54]

RN486

Drug Info

[55]

Modulator

[+] 2 Modulator drugs

CC-292

Drug Info

[15]

ONO-4059

Drug Info

[47]

Degrader

[+] 1 Degrader drugs

BGB-16673

Drug Info

[22]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

Top

Ligand Name: Dasatinib

Ligand Info

Structure Description

Structures of human Bruton's tyrosine kinase in active and inactive conformations suggests a mechanism of activation for TEC family kinases.

PDB:3K54

Method

X-ray diffraction

Resolution

1.94 Å

Mutation

Yes

[56]

PDB Sequence

YGSWEIDPKD

⁴⁰¹

LTFLKELGTG

⁴¹¹

QFGVVKYGKW

⁴²¹

RGQYDVAIKM

⁴³¹

IKEFIEEAKV

⁴⁴⁸

MMNLSHEKLV

⁴⁵⁸

QLYGVCTKQR

⁴⁶⁸

PIFIITEYMA

⁴⁷⁸

NGCLLNYLRE

⁴⁸⁸

MRHRFQTQQL

⁴⁹⁸

LEMCKDVCEA

⁵⁰⁸

MEYLESKQFL

⁵¹⁸

HRDLAARNCL

⁵²⁸

VNDQGVVKVS

⁵³⁸

DFGFPVRWSP

⁵⁶⁵

PEVLMYSKFS

⁵⁷⁵

SKSDIWAFGV

⁵⁸⁵

LMWEIYSLGK

⁵⁹⁵

MPYERFTNSE

⁶⁰⁵

TAEHIAQGLR

⁶¹⁵

LYRPHLASEK

⁶²⁵

VYTIMYSCWH

⁶³⁵

EKADERPTFK

⁶⁴⁵

ILLSNILDVM

⁶⁵⁵

DEE

Residue

Distance (Å)

LEU408

3.772

GLY409

4.796

PHE413

4.135

VAL416

4.088

ALA428

3.367

ILE429

4.025

LYS430

3.495

GLU445

3.320

MET449

3.940

VAL458

3.717

ILE472

3.599

Residue

Distance (Å)

ILE473

4.802

THR474

2.879

GLU475

3.432

TYR476

3.555

MET477

2.801

ALA478

3.107

ASN479

3.983

GLY480

3.425

LEU528

3.521

SER538

3.061

ASP539

4.354

Click to View More Binding Site Information of This Target and Ligand Pair

Ligand Name: Ibrutinib

Ligand Info

Structure Description

BTK1 SOAKED WITH IBRUTINIB-Rev

PDB:5P9I

Method

X-ray diffraction

Resolution

1.11 Å

Mutation

[57]

PDB Sequence

GLGYGSWEID

³⁹⁸

PKDLTFLKEL

⁴⁰⁸

GTGQFGVVKY

⁴¹⁸

GKWRGQYDVA

⁴²⁸

IKMIKEGSMS

⁴³⁸

EDEFIEEAKV

⁴⁴⁸

MMNLSHEKLV

⁴⁵⁸

QLYGVCTKQR

⁴⁶⁸

PIFIITEYMA

⁴⁷⁸

NGCLLNYLRE

⁴⁸⁸

MRHRFQTQQL

⁴⁹⁸

LEMCKDVCEA

⁵⁰⁸

MEYLESKQFL

⁵¹⁸

HRDLAARNCL

⁵²⁸

VNDQGVVKVS

⁵³⁸

DFGLSRYVLD

⁵⁴⁸

DEYTSSVGSK

⁵⁵⁸

FPVRWSPPEV

⁵⁶⁸

LMYSKFSSKS

⁵⁷⁸

DIWAFGVLMW

⁵⁸⁸

EIYSLGKMPY

⁵⁹⁸

ERFTNSETAE

⁶⁰⁸

HIAQGLRLYR

⁶¹⁸

PHLASEKVYT

⁶²⁸

IMYSCWHEKA

⁶³⁸

DERPTFKILL

⁶⁴⁸

SNILDVMDEE

⁶⁵⁸

Residue

Distance (Å)

LEU408

3.579

GLY409

4.000

THR410

3.926

GLY411

3.851

VAL416

3.729

ALA428

3.263

LYS430

3.249

MET449

3.466

VAL458

4.075

ILE472

3.959

THR474

3.342

GLU475

2.858

Residue

Distance (Å)

TYR476

3.718

MET477

2.986

ALA478

4.827

GLY480

3.317

CYS481

2.824

ASN484

3.085

LEU528

3.646

SER538

3.357

ASP539

3.100

PHE540

3.609

LEU542

4.043

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Mixed lineage kinase 1 (MAP3K9)	PF00069 ; PF14604	29.603 (82/277)	1.10E-26
Serine/threonine-protein kinase 26 (STK26)	PF00069	34.171 (68/199)	2.59E-23
Serine/threonine-protein kinase ULK1 (ULK1)	PF12063 ; PF00069	28.959 (64/221)	1.67E-22
Aurora kinase A (AURKA)	PF00069	24.710 (64/259)	2.15E-22
Serine/threonine-protein kinase ULK2 (ULK2)	PF12063 ; PF00069	29.412 (65/221)	1.20E-21
Serine/threonine-protein kinase 24 (STK24)	PF00069	28.409 (75/264)	8.06E-21
Aurora kinase C (AURKC)	PF00069	26.667 (64/240)	1.59E-20
MAP/microtubule affinity-regulating kinase 4 (MARK4)	PF02149 ; PF00069 ; PF00627 More >>	27.064 (59/218)	2.65E-20
Salt-inducible kinase 2 (SIK2)	PF00069	27.027 (60/222)	2.75E-20
Serine/threonine-protein kinase Nek10 (NEK10)	PF00069	28.467 (78/274)	2.90E-20
Putative serine/threonine-protein kinase PRKY (PRKY)	PF00069	29.293 (58/198)	3.61E-20
Omphalocele kinase 1 (NUAK1)	PF00069	28.505 (61/214)	3.61E-20
cAMP-dependent protein kinase catalytic subunit PRKX (PRKX)	PF00069	29.293 (58/198)	5.75E-20
Microtubule affinity regulating kinase 3 (MARK3)	PF02149 ; PF00069 ; PF00627 More >>	27.928 (62/222)	1.03E-19
Protein kinase C delta (PRKCD)	PF00130 ; PF00069 ; PF00433 More >>	26.939 (66/245)	1.14E-19
NUAK family SNF1-like kinase 2 (NUAK2)	PF00069	26.389 (57/216)	1.57E-19
BR serine/threonine kinase 2 (BRSK2)	PF00069	24.206 (61/252)	2.87E-19
Serine/threonine-protein kinase MARK2 (MARK2)	PF02149 ; PF00069 ; PF00627 More >>	26.606 (58/218)	5.66E-19
Serine/threonine-protein kinase 25 (STK25)	PF00069	29.500 (59/200)	8.41E-19
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	PF00069 ; PF12721	28.571 (82/287)	9.12E-19
PAK-2 protein kinase (PAK2)	PF00786 ; PF00069	29.952 (62/207)	9.27E-19
Protein kinase C beta (PRKCB)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	25.862 (60/232)	9.49E-19
Serine/threonine-protein kinase ICK (CILK1)	PF00069	30.457 (60/197)	1.33E-18
Ribosomal protein S6 kinase alpha-1 (RSK1)	PF00069 ; PF00433	24.806 (64/258)	1.82E-18
BR serine/threonine kinase 1 (BRSK1)	PF00069	24.280 (59/243)	2.08E-18
Serine/threonine-protein kinase MARK1 (MARK1)	PF02149 ; PF00069 ; PF00627 More >>	26.818 (59/220)	2.72E-18
Serine/threonine-protein kinase PAK 6 (PAK6)	PF00786 ; PF00069	27.230 (58/213)	2.87E-18
SNF-related serine/threonine-protein kinase (SNRK)	PF00069	28.169 (60/213)	3.22E-18
SIK family kinase 3 (SIK3)	PF00069	26.724 (62/232)	3.25E-18
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	PF00069	27.336 (79/289)	3.47E-18
Protein kinase C epsilon (PRKCE)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	26.809 (63/235)	3.51E-18
Ribosomal protein S6 kinase alpha-3 (RSK3)	PF00069 ; PF00433	25.911 (64/247)	4.73E-18
Serine/threonine-protein kinase 10 (STK10)	PF00069 ; PF12474	26.923 (56/208)	5.42E-18
MST-1 protein kinase (STK4)	PF11629 ; PF00069	26.587 (67/252)	5.84E-18
Serine/threonine-protein kinase MAK (MAK)	PF00069	30.102 (59/196)	9.38E-18
Protein kinase C alpha (PRKCA)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	25.431 (59/232)	9.91E-18
Serine/threonine-protein kinase 3 (STK3)	PF11629 ; PF00069	27.200 (68/250)	1.03E-17
Myosin light chain kinase 2 (MYLK2)	PF00069	28.436 (60/211)	1.18E-17
Ribosomal protein S6 kinase alpha-6 (RSK6)	PF00069 ; PF00433	26.255 (68/259)	1.32E-17
Serine/threonine-protein kinase TAO2 (TAOK2)	PF00069	27.652 (73/264)	1.36E-17
Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)	PF00069	29.237 (69/236)	1.50E-17
ERK activator kinase 2 (MEK2)	PF00069	29.126 (60/206)	1.52E-17
NIMA-related kinase 1 (NEK1)	PF00069	28.643 (57/199)	1.85E-17
Putative serine/threonine-protein kinase SIK1B (SIK1B)	PF00069	26.728 (58/217)	3.84E-17
Salt-inducible kinase 1 (SIK1)	PF00069	26.728 (58/217)	4.05E-17
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	PF16579 ; PF00069	24.898 (61/245)	5.29E-17
Aurora kinase B (AURKB)	PF00069	26.639 (65/244)	5.48E-17
Ribosomal protein S6 kinase alpha-2 (RSK2)	PF00069 ; PF00433	24.603 (62/252)	6.18E-17
PAK-1 protein kinase (PAK1)	PF00786 ; PF00069	28.986 (60/207)	6.67E-17
Protein kinase C eta type (PRKCH)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	26.939 (66/245)	8.56E-17
Oxidative stress responsive 1 (OXSR1)	PF12202 ; PF00069	25.676 (57/222)	9.79E-17
Myosin light chain kinase family member 4 (MYLK4)	PF00069	28.846 (60/208)	1.21E-16
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	PF16579 ; PF00069	26.016 (64/246)	1.30E-16
Proto-oncogene serine/threonine-protein kinase mos (MOS)	PF00069	26.230 (80/305)	1.51E-16
Cyclin-dependent kinase-like 3 (CDKL3)	PF00069	30.102 (59/196)	1.57E-16
Myosin light chain kinase 3 (MYLK3)	PF00069	29.808 (62/208)	1.66E-16
Serine/threonine-protein kinase Nek11 (NEK11)	PF00069	26.500 (53/200)	1.69E-16
Protein kinase C theta (PRKCQ)	PF00130 ; PF00069 ; PF00433 More >>	24.303 (61/251)	1.74E-16
Cyclin-dependent kinase 18 (CDK18)	PF00069	27.632 (63/228)	1.78E-16
Serine/threonine-protein kinase PAK 3 (PAK3)	PF00786 ; PF00069	28.502 (59/207)	1.80E-16
Death-associated protein kinase 3 (DAPK3)	PF00069	24.658 (54/219)	2.04E-16
Serine/threonine-protein kinase PAK 5 (PAK5)	PF00786 ; PF00069	25.243 (52/206)	2.29E-16
Ste-20-related kinase (STK39)	PF12202 ; PF00069	27.143 (57/210)	2.36E-16
TAO kinase 1 (TAOK1)	PF00069	26.493 (71/268)	2.44E-16
PAK-4 protein kinase (PAK4)	PF00786 ; PF00069	25.238 (53/210)	3.98E-16
Doublecortin-like kinase 3 (DCLK3)	PF00069	28.723 (54/188)	4.91E-16
Death-associated protein kinase 2 (DAPK2)	PF00069	24.658 (54/219)	5.23E-16
ERK activator kinase 1 (MEK1)	PF00069	30.097 (62/206)	5.30E-16
STE20-related serine/threonine-protein kinase (SLK)	PF00069 ; PF12474	27.962 (59/211)	5.35E-16
Hormonally up-regulated neu tumor-associated kinase (HUNK)	PF00069	25.490 (52/204)	6.61E-16
Putative 3-phosphoinositide-dependent protein kinase 2 (PDPK2P)	PF00069	27.000 (54/200)	6.79E-16
Death-associated protein kinase 1 (DAPK1)	PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF00069 More >>	26.697 (59/221)	9.00E-16
Serine/threonine-protein kinase Nek3 (NEK3)	PF00069	23.438 (60/256)	1.17E-15
Polo-like kinase 4 (PLK4)	PF00069 ; PF18190 ; PF18409 More >>	24.803 (63/254)	1.21E-15
Phosphoinositide dependent protein kinase-1 (PDPK1)	PF14593 ; PF00069	27.000 (54/200)	1.29E-15
Protein kinase C iota (PRKCI)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	24.364 (67/275)	1.36E-15
NIMA-related kinase 2 (NEK2)	PF00069	26.715 (74/277)	1.59E-15
SPS1/STE20-related protein kinase YSK4 (YSK4)	PF00069	25.287 (66/261)	1.69E-15
Serine/threonine-protein kinase Sgk2 (SGK2)	PF00069 ; PF00433	29.091 (64/220)	1.78E-15
Cyclin-dependent kinase 12 (CDK12)	PF00069	25.500 (51/200)	1.86E-15
Testis-specific serine kinase 2 (TSSK2)	PF00069	28.571 (58/203)	2.69E-15
Cyclin-dependent kinase 13 (CDK13)	PF12330 ; PF00069	23.629 (56/237)	2.77E-15
Serine/threonine-protein kinase Sgk1 (SGK1)	PF00069 ; PF00433	24.242 (56/231)	2.89E-15
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)	PF00069	25.551 (58/227)	3.03E-15
MEK kinase kinase 1 (MAP4K1)	PF00780 ; PF00069	27.053 (56/207)	3.10E-15
ERK activator kinase 7 (MAP2K7)	PF00069	25.271 (70/277)	3.59E-15
Cyclin-dependent kinase 17 (CDK17)	PF12330 ; PF00069	26.540 (56/211)	4.19E-15
Maternal embryonic leucine zipper kinase (MELK)	PF02149 ; PF00069	27.500 (55/200)	4.29E-15
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	PF00069	26.222 (59/225)	4.69E-15
Cyclin-dependent kinase 1 (CDK1)	PF00069	28.856 (58/201)	6.04E-15
ERK activator kinase 5 (MAP2K5)	PF00564 ; PF00069	25.769 (67/260)	6.23E-15
Cyclin-dependent kinase 16 (CDK16)	PF12330 ; PF00069	25.778 (58/225)	7.59E-15
Serine/threonine-protein kinase Nek4 (NEK4)	PF00069	24.335 (64/263)	7.59E-15
Protein kinase C gamma (PRKCG)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	22.134 (56/253)	7.65E-15
cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)	PF00069	25.110 (57/227)	7.81E-15
NIMA-related kinase 6 (NEK6)	PF00069	24.645 (52/211)	8.79E-15
Protein kinase C zeta (PRKCZ)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	23.387 (58/248)	9.05E-15
Cyclin-dependent kinase-like 2 (CDKL2)	PF00069	27.979 (54/193)	9.69E-15
Cyclin-dependent kinase-like 4 (CDKL4)	PF00069	26.531 (52/196)	1.34E-14
Serine/threonine-protein kinase Nek5 (NEK5)	PF00069	22.989 (60/261)	1.47E-14
NIMA-related kinase 7 (NEK7)	PF00069	23.246 (53/228)	1.82E-14
Serine/threonine-protein kinase NIM1 (NIM1K)	PF00069	24.498 (61/249)	1.95E-14
Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	26.613 (66/248)	2.08E-14
Cyclin-dependent kinase 3 (CDK3)	PF00069	28.713 (58/202)	2.11E-14
Serine/threonine-protein kinase 17B (STK17B)	PF00069	26.641 (69/259)	2.44E-14
Serine/threonine-protein kinase Nek9 (NEK9)	PF00069 ; PF00415	24.632 (67/272)	3.28E-14
MAPK/ERK kinase kinase 3 (MAP3K3)	PF00564 ; PF00069	27.848 (66/237)	4.62E-14
Cyclin-dependent kinase 15 (CDK15)	PF00069	28.426 (56/197)	4.64E-14
Serine/threonine-protein kinase WNK1 (WNK1)	PF12202 ; PF00069	26.217 (70/267)	4.85E-14
Fused homolog (STK36)	PF13646 ; PF00069	27.136 (54/199)	5.53E-14
Serine/threonine-protein kinase D2 (PRKD2)	PF00130 ; PF00069	27.778 (55/198)	5.84E-14
Yet another novel kinase 2 (STK32B)	PF00069	26.471 (63/238)	9.57E-14
Serine/threonine-protein kinase Nek8 (NEK8)	PF00069 ; PF00415	27.136 (54/199)	1.06E-13
Ribosomal protein S6 kinase alpha-4 (RPS6KA4)	PF00069 ; PF00433	23.478 (54/230)	1.09E-13
Cyclin-dependent kinase 6 (CDK6)	PF00069	27.723 (56/202)	1.15E-13
Unc-51 like kinase 3 (ULK3)	PF04212 ; PF00069	26.667 (64/240)	1.39E-13
MAPK/ERK kinase kinase 2 (MAP3K2)	PF00564 ; PF00069	29.464 (66/224)	1.74E-13
WNK lysine-deficient protein kinase 3 (WNK3)	PF12202 ; PF00069	25.000 (68/272)	2.17E-13
TGF-beta receptor type I (TGFBR1)	PF01064 ; PF00069 ; PF08515 More >>	25.685 (75/292)	2.17E-13
Ribosomal protein S6 kinase beta-1 (S6K1)	PF00069 ; PF00433	24.800 (62/250)	2.28E-13
Apoptosis signal-regulating kinase 1 (MAP3K5)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	26.255 (68/259)	2.30E-13
Cyclin-dependent kinase 9 (CDK9)	PF00069	28.436 (60/211)	2.43E-13
Testis-specific serine/threonine-protein kinase 1 (TSSK1B)	PF00069	27.232 (61/224)	2.46E-13
Cyclin-dependent kinase 14 (CDK14)	PF00069	27.551 (54/196)	2.53E-13
Serine/threonine-protein kinase Sgk3 (SGK3)	PF00069 ; PF00433 ; PF00787 More >>	25.112 (56/223)	2.59E-13
Cytoplasmic DRAK1 (STK17A)	PF00069	25.806 (56/217)	2.99E-13
TAO kinase 3 (TAOK3)	PF00069	26.471 (63/238)	3.05E-13
Calcium/calmodulin-dependent protein kinase type 1G (CAMK1G)	PF00069	26.484 (58/219)	4.17E-13
Ribosomal protein S6 kinase alpha-5 (RSK5)	PF00069 ; PF00433	24.454 (56/229)	4.24E-13
PKC-delta-interacting protein kinase (RIPK4)	PF12796 ; PF00069	25.912 (71/274)	4.33E-13
Cyclin-dependent kinase 2 (CDK2)	PF00069	27.000 (54/200)	4.38E-13
Cyclin-dependent kinase-like 5 (CDKL5)	PF00069	23.711 (46/194)	4.64E-13
Serine/threonine-protein kinase 32A (STK32A)	PF00069	23.293 (58/249)	5.91E-13
TRAF2 and NCK interacting kinase (TNIK)	PF00780 ; PF00069	24.528 (52/212)	6.41E-13
Mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5)	PF00780 ; PF00069	25.373 (51/201)	6.95E-13
MEK kinase kinase 3 (MAP4K3)	PF00780 ; PF00069	24.378 (49/201)	7.14E-13
Serine/threonine-protein kinase pim-1 (PIM1)	PF00069	27.092 (68/251)	8.10E-13
Stress-activated protein kinase 2a (p38 alpha)	PF00069	24.402 (51/209)	9.88E-13
Cyclin-dependent kinase 5 (CDK5)	PF00069	24.201 (53/219)	1.13E-12
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	PF00069	24.211 (69/285)	1.14E-12
Serine/threonine-protein kinase WNK4 (WNK4)	PF12202 ; PF00069	26.838 (73/272)	1.29E-12
Protein kinase G1 (PRKG1)	PF00027 ; PF16808 ; PF00069 More >>	25.778 (58/225)	1.31E-12
Myosin light kinase (MYLK)	PF16620 ; PF00041 ; PF07679 ; PF00069 More >>	27.404 (57/208)	1.36E-12
Activin receptor type IB (ACVR1B)	PF01064 ; PF00069 ; PF08515 More >>	27.358 (58/212)	1.80E-12
Polo-like kinase 2 (PLK2)	PF00069 ; PF00659	26.108 (53/203)	2.40E-12
Cyclin-dependent kinase-like 1 (CDKL1)	PF00069	26.866 (54/201)	2.87E-12
Cyclin-dependent kinase 7 (CDK7)	PF00069	27.404 (57/208)	3.07E-12
Extracellular signal-regulated kinase 2 (ERK2)	PF00069	26.190 (55/210)	3.21E-12
Serine/threonine-protein kinase H1 (PSKH1)	PF00069	26.636 (57/214)	3.36E-12
Protein kinase N1 (PKN1)	PF02185 ; PF00069 ; PF00433 More >>	25.397 (64/252)	4.00E-12
Serine/threonine-protein kinase 33 (STK33)	PF00069	25.333 (57/225)	5.01E-12
Ribosomal protein S6 kinase beta-2 (RPS6KB2)	PF00069 ; PF00433	22.308 (58/260)	5.78E-12
Stress-activated protein kinase 2b (p38 beta)	PF00069	25.121 (52/207)	6.57E-12
Extracellular signal-regulated kinase 1 (ERK1)	PF00069	26.540 (56/211)	6.67E-12
Serine/threonine-protein kinase 32C (STK32C)	PF00069	24.370 (58/238)	7.72E-12
MEK kinase kinase 2 (MAP4K2)	PF00780 ; PF00069	24.880 (52/209)	7.74E-12
Calcium/calmodulin-dependent protein kinase type 1B (PNCK)	PF00069	26.984 (51/189)	1.02E-11
Protein kinase G2 (PRKG2)	PF00027 ; PF00069	24.215 (54/223)	1.41E-11
Serine/threonine-protein kinase H2 (PSKH2)	PF00069	26.087 (60/230)	1.62E-11
Myotonin-protein kinase (DMPK)	PF08826 ; PF00069	24.576 (58/236)	2.21E-11
Striated muscle preferentially expressed protein kinase (SPEG)	PF07679 ; PF00069 ; PF16650 More >>	26.728 (58/217)	2.32E-11
Tyrosine-protein kinase EIF2AK2 (p68)	PF00035 ; PF00069	23.043 (53/230)	3.01E-11
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	PF18397 ; PF12179 ; PF00069 More >>	25.541 (59/231)	3.12E-11
Cyclin-dependent kinase 10 (CDK10)	PF00069	28.780 (59/205)	4.24E-11
Serine/threonine-protein kinase STK11 (STK11)	PF00069	27.473 (50/182)	4.69E-11
Misshapen-like kinase 1 (MINK1)	PF00780 ; PF00069	24.057 (51/212)	5.01E-11
TGF-beta-stimulated factor 1 (STK16)	PF00069	20.641 (58/281)	5.18E-11
Apoptosis signal-regulating kinase 2 (MAP3K6)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	26.027 (57/219)	6.25E-11
CDC42 binding protein kinase alpha (DMPK-like alpha)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 ; PF00433 More >>	24.286 (51/210)	7.44E-11
Myosin-IIIa (MYO3A)	PF00612 ; PF00063 ; PF00069 More >>	22.509 (61/271)	9.33E-11
Cyclin-dependent kinase 11A (CDK11A)	PF00069	25.126 (50/199)	9.81E-11
Calcium/calmodulin-dependent protein kinase type 1D (CAMK1D)	PF00069	24.576 (58/236)	1.00E-10
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	PF00069	28.000 (63/225)	1.03E-10
Testis-specific serine/threonine-protein kinase 6 (TSSK6)	PF00069	26.923 (56/208)	1.07E-10
Serine/threonine-protein kinase SBK1 (SBK1)	PF00069	22.535 (48/213)	1.13E-10
Leucine-rich repeat kinase 2 (LRRK2)	PF16095 ; PF12799 ; PF13855 ; PF00069 ; PF08477 More >>	24.800 (62/250)	1.20E-10
Serine/threonine-protein kinase WNK2 (WNK2)	PF12202 ; PF00069	26.568 (72/271)	1.40E-10
MAP kinase p38 (MAPK12)	PF00069	26.961 (55/204)	1.41E-10
Mitogen-activated protein kinase 6 (MAPK6)	PF00069	27.391 (63/230)	1.46E-10
Cyclin-dependent kinase 11B (CDK11B)	PF00069	24.623 (49/199)	1.59E-10
Calcium/calmodulin-dependent protein kinase type IV (CAMK4)	PF00069	25.269 (47/186)	1.79E-10
Extracellular signal-regulated kinase 5 (ERK5)	PF00069	24.390 (50/205)	2.02E-10
Protein kinase N2 (PKN2)	PF02185 ; PF00069 ; PF00433 More >>	23.735 (61/257)	2.29E-10
CaM-kinase IV kinase (CAMKK1)	PF00069	26.875 (43/160)	2.50E-10
Cyclin-dependent kinase 4 (CDK4)	PF00069	23.529 (48/204)	2.92E-10
Serine/threonine-protein kinase MRCK beta (CDC42BPB)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 More >>	23.810 (50/210)	3.22E-10
Mitogen-activated protein kinase 13 (MAPK13)	PF00069	25.472 (54/212)	3.24E-10
Serine/threonine-protein kinase NLK (NLK)	PF00069	26.733 (54/202)	3.35E-10
MAPK-activated protein kinase 3 (MAPKAPK3)	PF00069	27.451 (42/153)	3.51E-10
Obscurin (OBSCN)	PF00041 ; PF07679 ; PF00612 ; PF00069 ; PF00621 More >>	25.688 (56/218)	3.53E-10
Serine/threonine-protein kinase greatwall (MASTL)	PF00069	25.490 (39/153)	3.65E-10
Myosin-IIIb (MYO3B)	PF00612 ; PF00063 ; PF00069 More >>	24.171 (51/211)	4.39E-10
Polo-like kinase 1 (PLK1)	PF00069 ; PF00659	27.381 (46/168)	4.94E-10
MAPK/ERK kinase kinase 1 (MAP3K1)	PF00069	20.229 (53/262)	5.12E-10
Doublecortin-like kinase 1 (DCLK1)	PF03607 ; PF00069	24.211 (46/190)	5.81E-10
Serine/threonine-protein kinase PLK3 (PLK3)	PF00069 ; PF00659	23.280 (44/189)	6.14E-10
Rho-associated protein kinase 1 (ROCK1)	PF00069 ; PF08912	23.904 (60/251)	6.30E-10
Cyclin-G-associated kinase (GAK)	PF00069 ; PF10409	23.171 (57/246)	6.93E-10
Testis-specific serine/threonine-protein kinase 4 (TSSK4)	PF00069	26.267 (57/217)	7.29E-10
Nik-related protein kinase (NRK)	PF00780 ; PF00069	23.214 (52/224)	7.52E-10
Bone morphogenetic protein receptor (BMPR2)	PF01064 ; PF00069	25.214 (59/234)	8.28E-10
Mitogen-activated protein kinase 15 (MAPK15)	PF00069	25.837 (54/209)	1.05E-09
Stress-activated protein kinase JNK2 (JNK2)	PF00069	25.628 (51/199)	1.18E-09
Serine/threonine-protein kinase pim-2 (PIM2)	PF00069	24.615 (64/260)	1.22E-09
MAPK/ERK kinase kinase 4 (MAP3K4)	PF19431 ; PF00069	24.855 (43/173)	1.60E-09
Stress-activated protein kinase JNK3 (JNK3)	PF00069	27.000 (54/200)	1.61E-09
Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)	PF18397 ; PF12179 ; PF00069 More >>	24.545 (54/220)	1.61E-09
Ribosomal protein S6 kinase-related protein (RSKR)	PF00069	25.325 (39/154)	1.72E-09
Doublecortin-like kinase 2 (DCLK2)	PF03607 ; PF00069	25.854 (53/205)	2.20E-09
Stress-activated protein kinase JNK1 (JNK1)	PF00069	26.633 (53/199)	2.25E-09
MAPK/MAK/MRK overlapping kinase (MOK)	PF00069	24.752 (50/202)	2.38E-09
Calmodulin-dependent kinase II (CAMKK2)	PF00069	26.901 (46/171)	2.62E-09
NDR2 protein kinase (STK38L)	PF00069 ; PF00433	22.358 (55/246)	2.66E-09
Calcium/calmodulin-dependent protein kinase type II subunit gamma (CAMK2G)	PF08332 ; PF00069	24.878 (51/205)	2.85E-09
Rho-associated protein kinase 2 (ROCK2)	PF00069 ; PF08912	24.219 (62/256)	3.00E-09
Dual-specificity tyrosine-phosphorylation regulated kinase 3 (DYRK3)	PF00069	24.242 (48/198)	3.06E-09
Mitogen-activated protein kinase 4 (MAPK4)	PF00069	25.670 (67/261)	3.61E-09
BMP-2-inducible protein kinase (BMP2K)	PF15282 ; PF00069	25.000 (54/216)	3.85E-09
Cyclin-dependent kinase 20 (CDK20)	PF00069	22.500 (45/200)	4.04E-09
Serine/threonine-protein kinase MRCK gamma (CDC42BPG)	PF00130 ; PF00780 ; PF08826 ; PF00069 More >>	24.880 (52/209)	4.38E-09
NF-kappa-B-activating kinase (TBK1)	PF00069 ; PF18394 ; PF18396 More >>	26.389 (57/216)	4.87E-09
G protein-coupled receptor kinase 4 (GRK4)	PF00069 ; PF00615	23.864 (42/176)	4.91E-09
NDR1 protein kinase (STK38)	PF00069 ; PF00433	22.800 (57/250)	5.05E-09
IL-1 receptor-associated kinase 1 (IRAK1)	PF00531 ; PF00069	24.402 (51/209)	5.29E-09
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)	PF00069 ; PF18394 ; PF18396 More >>	26.016 (64/246)	6.52E-09
G protein-coupled receptor kinase 6 (GRK6)	PF00069 ; PF00615	25.466 (41/161)	6.52E-09
Protein kinase N3 (PKN3)	PF02185 ; PF00069 ; PF00433 More >>	26.244 (58/221)	7.88E-09
Phosphorylase kinase testis gamma 2 (PHKG2)	PF00069	22.477 (49/218)	9.92E-09
Calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B)	PF08332 ; PF00069	25.000 (50/200)	1.02E-08
MAPK-activated protein kinase 2 (MAPKAPK2)	PF00069	25.654 (49/191)	1.10E-08
Checkpoint kinase-1 (CHK1)	PF00069	23.113 (49/212)	1.20E-08
PAS domain-containing serine/threonine-protein kinase (PASK)	PF13426 ; PF00069	20.229 (53/262)	1.22E-08
Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1)	PF12796 ; PF16095 ; PF00069 ; PF08477 More >>	23.894 (54/226)	1.26E-08
Serine/threonine-protein kinase tousled-like 2 (TLK2)	PF00069	26.316 (45/171)	1.59E-08
G protein-coupled receptor kinase 5 (GRK5)	PF00069 ; PF00615	25.101 (62/247)	1.93E-08
CDC-like kinase 1 (CLK1)	PF00069	25.000 (60/240)	2.10E-08
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A)	PF08332 ; PF00069	25.248 (51/202)	2.37E-08
Serine/threonine-protein kinase NIK (MAP3K14)	PF00069	23.902 (49/205)	2.81E-08
Testis-specific serine/threonine-protein kinase 3 (TSSK3)	PF00069	27.619 (58/210)	3.92E-08
Adaptor-associated kinase 1 (AAK1)	PF00069	26.119 (35/134)	4.25E-08
CDC-like kinase 4 (CLK4)	PF00069	25.000 (60/240)	4.31E-08
CDC-like kinase 2 (CLK2)	PF00069	24.390 (60/246)	4.59E-08
Titin (TTN)		20.000 (43/215)	4.60E-08
PRKR-like endoplasmic reticulum kinase (PERK)	PF00069	33.000 (33/100)	4.86E-08
MEK kinase kinase 4 (MAP4K4)	PF00780 ; PF00069	23.113 (49/212)	5.28E-08
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)	PF08332 ; PF00069	24.752 (50/202)	6.60E-08
Serine/threonine-protein kinase tousled-like 1 (TLK1)	PF00069	26.012 (45/173)	7.56E-08
Dual-specificity tyrosine-phosphorylation regulated kinase 2 (DYRK2)	PF00069	23.350 (46/197)	8.53E-08
Dual-specificity tyrosine-phosphorylation regulated kinase 1B (DYRK1B)	PF00069	25.871 (52/201)	8.59E-08
Microtubule-associated serine/threonine-protein kinase 4 (MAST4)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	23.963 (52/217)	8.61E-08
PDZ binding kinase (PBK)	PF00069	24.176 (44/182)	9.61E-08
Microtubule-associated serine/threonine-protein kinase 3 (MAST3)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	23.853 (52/218)	1.02E-07
Glycogen synthase kinase-3 alpha (GSK-3A)	PF00069	24.201 (53/219)	1.10E-07
Serine/threonine-protein kinase PRP4 homolog (PRPF4B)	PF00069	29.592 (29/98)	2.22E-07
Microtubule-associated serine/threonine-protein kinase 1 (MAST1)	PF08926 ; PF17820 ; PF00069 More >>	22.026 (50/227)	2.51E-07
PIM-3 protein kinase (PIM3)	PF00069	24.762 (52/210)	2.88E-07
Rhodopsin kinase GRK1 (GRK1)	PF00069 ; PF00615	25.143 (44/175)	3.08E-07
Serine/threonine-protein kinase SBK2 (SBK2)	PF00069	24.138 (49/203)	3.19E-07
Microtubule-associated serine/threonine-protein kinase 2 (MAST2)	PF08926 ; PF17820 ; PF00069 More >>	22.624 (50/221)	3.48E-07
Homeodomain-interacting protein kinase 4 (HIPK4)	PF00069	23.707 (55/232)	6.32E-07
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (PHKG1)	PF00069	21.591 (38/176)	8.02E-07
Serine/threonine-protein kinase ULK4 (ULK4)	PF00069	22.026 (50/227)	8.21E-07
Dual-specificity tyrosine-phosphorylation regulated kinase 4 (DYRK4)	PF00069	25.366 (52/205)	9.60E-07
Serine/threonine kinase-like domain-containing protein STKLD1 (STKLD1)	PF00069	29.204 (33/113)	1.33E-06
Serine/threonine-protein kinase cot (COT)	PF00069	25.175 (36/143)	1.48E-06
Serine/threonine-protein kinase LATS1 (LATS1)	PF00069 ; PF00627	20.553 (52/253)	1.71E-06
Homeodomain-interacting protein kinase 3 (HIPK3)	PF00069	25.253 (50/198)	1.88E-06
Large tumor suppressor homolog 2 (LATS2)	PF00069 ; PF00433	20.949 (53/253)	1.90E-06
TBC domain-containing protein kinase-like protein (TBCK)	PF00069 ; PF00566 ; PF00581 More >>	21.264 (37/174)	2.62E-06
Homeodomain interacting protein kinase 2 (HIPK2)	PF00069	24.121 (48/199)	2.75E-06
SH3 and cysteine-rich domain-containing protein (STAC)	PF00130 ; PF07653 ; PF14604 ; PF16664 More >>	26.957 (31/115)	3.01E-06
CDC-like kinase 3 (CLK3)	PF00069	23.377 (54/231)	3.04E-06
MAP kinase signal-integrating kinase 2 (MKNK2)	PF00069	25.899 (36/139)	3.25E-06
Cyclin-dependent kinase 19 (CDK19)	PF00069	25.837 (54/209)	3.85E-06
IL-1 receptor-associated kinase 3 (IRAK3)	PF00531 ; PF00069	23.171 (38/164)	4.03E-06
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)	PF00069	29.365 (37/126)	5.25E-06
Serine/threonine-protein kinase Chk2 (RAD53)	PF00498 ; PF00069	25.620 (62/242)	5.34E-06
SH3 and cysteine-rich domain-containing protein 2 (STAC2)	PF00130 ; PF14604 ; PF16664 More >>	38.000 (19/50)	5.35E-06
Casein kinase I gamma-3 (CSNK1G3)	PF12605 ; PF00069	24.180 (59/244)	5.46E-06
Dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A)	PF00069	26.000 (52/200)	7.60E-06
Serine/threonine-protein kinase 35 (STK35)	PF00069	24.848 (41/165)	1.06E-05
Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)	PF00611 ; PF14604	32.530 (27/83)	1.40E-05
Casein kinase I gamma-1 (CSNK1G1)	PF12605 ; PF00069	26.168 (56/214)	1.77E-05
Serine/threonine-protein kinase Kist (UHMK1)	PF00069 ; PF00076	21.525 (48/223)	2.09E-05
Homeodomain-interacting protein kinase 1 (HIPK1)	PF00069	23.737 (47/198)	2.26E-05
Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4)	PF12745 ; PF00069 ; PF05773 ; PF13393 More >>	26.950 (38/141)	3.00E-05
Activin receptor type IIA (ACVR2A)	PF01064 ; PF00069	22.059 (45/204)	3.40E-05
Dual specificity protein kinase TTK (MPS1)	PF00069	23.171 (38/164)	4.74E-05
Cyclin-dependent kinase 8 (CDK8)	PF00069	24.044 (44/183)	5.37E-05
CaM kinase-like vesicle-associated protein (CAMKV)	PF00069	22.293 (35/157)	5.94E-05
Anti-mullerian hormone II receptor (AMHR2)	PF00069	20.172 (47/233)	8.77E-05
Tau-tubulin kinase (TTBK1)	PF00069	19.930 (57/286)	1.36E-04
Interleukin-1 receptor-associated kinase-like 2 (IRAK2)	PF00531 ; PF00069	20.202 (40/198)	1.87E-04
AP-4 complex accessory subunit RUSC1 (RUSC1)	PF02759 ; PF14604	29.358 (32/109)	2.37E-04
Tau-tubulin kinase 2 (TTBK2)	PF00069	20.816 (51/245)	2.47E-04
Serine/threonine-protein kinase PDIK1L (PDIK1L)	PF00069	23.611 (34/144)	3.01E-04
Activin receptor type IIB (ACVR2B)	PF01064 ; PF00069	23.661 (53/224)	3.34E-04
STE20-related kinase adapter protein beta (STRADB)	PF00069	23.438 (45/192)	3.80E-04
STE20-related kinase adapter protein alpha (STRADA)	PF00069	20.732 (34/164)	5.15E-04
Nostrin (NOSTRIN)	PF00611 ; PF14604	36.765 (25/68)	5.53E-04
Casein kinase I gamma-2 (CSNK1G2)	PF12605 ; PF00069	24.138 (56/232)	5.55E-04
Casein kinase II alpha prime (CSNK2A2)	PF00069	27.049 (33/122)	5.58E-04
Membrane-associated kinase (PKMYT1)	PF00069	22.018 (48/218)	6.26E-04
Protein kinase C and casein kinase substrate in neurons protein 1 (PACSIN1)	PF00611 ; PF14604	43.396 (23/53)	1.00E-03
Ribosomal protein S6 kinase-like 1 (RPS6KL1)	PF04212 ; PF00069	26.804 (26/97)	2.00E-03
Wee1-like protein kinase 2 (WEE2)	PF00069	20.213 (57/282)	2.00E-03
Casein kinase I delta (CSNK1D)	PF00069	24.576 (29/118)	2.00E-03
SH3 domain-containing kinase-binding protein 1 (SH3KBP1)	PF14604	31.646 (25/79)	2.00E-03
RIMS-binding protein 2 (RIMBP2)	PF07653 ; PF14604	31.429 (22/70)	2.00E-03
Click to Show/Hide the Information of Human Similarity Proteins


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
NF-kappa B signaling pathway	hsa04064	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Osteoclast differentiation	hsa04380	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy
Platelet activation	hsa04611	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
B cell receptor signaling pathway	hsa04662	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Fc epsilon RI signaling pathway	hsa04664	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	19	Degree centrality	2.04E-03	Betweenness centrality	7.89E-04
Closeness centrality	2.25E-01	Radiality	1.40E+01	Clustering coefficient	2.22E-01
Neighborhood connectivity	3.07E+01	Topological coefficient	9.41E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Drug Resistance
Mutation (DRM)

Drug Resistance Mutation Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 6 KEGG Pathways

NF-kappa B signaling pathway

Osteoclast differentiation

Platelet activation

B cell receptor signaling pathway

Fc epsilon RI signaling pathway

Primary immunodeficiency

Panther Pathway

[+] 1 Panther Pathways

B cell activation

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Fc Epsilon Receptor I Signaling in Mast Cells

PID Pathway

[+] 5 PID Pathways

Fc-epsilon receptor I signaling in mast cells

BCR signaling pathway

FAS (CD95) signaling pathway

Class I PI3K signaling events

EPO signaling pathway

Reactome

[+] 8 Reactome Pathways

MyD88:Mal cascade initiated on plasma membrane

Regulation of actin dynamics for phagocytic cup formation

DAP12 signaling

FCERI mediated Ca+2 mobilization

MyD88 deficiency (TLR2/4)

IRAK4 deficiency (TLR2/4)

RHO GTPases Activate WASPs and WAVEs

Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

WikiPathways

[+] 8 WikiPathways

Kit receptor signaling pathway

MyD88:Mal cascade initiated on plasma membrane

Signaling by the B Cell Receptor (BCR)

DAP12 interactions

B Cell Receptor Signaling Pathway

TSLP Signaling Pathway

Regulation of toll-like receptor signaling pathway

IL-5 Signaling Pathway

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials. Curr Hematol Malig Rep. 2013 Mar;8(1):1-6.

REF 2

2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.

REF 3

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6912).

REF 4

Janssen's IMBRUVICA (ibrutinib) Receives Additional European Commission Approval for the Treatment of Waldenstrom's Macroglobulinemia. Janssen-Cilag International NV (Janssen). Jul 10, 2015.

REF 5

ClinicalTrials.gov (NCT01833039) An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma. U.S. National Institutes of Health.

REF 6

FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216059.

REF 7

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019

REF 8

ClinicalTrials.gov (NCT04586023) Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Relapsing Multiple Sclerosis (RMS) (FENhance). U.S. National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT04578613) ICP-022 Versus Chlorambucil Combined With Rituximab in the Treatment of Untreated CLL/SLL. U.S. National Institutes of Health.

REF 10

ClinicalTrials.gov (NCT04411641) A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis. U.S.National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT04728893) Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies (MK-1026-003). U.S. National Institutes of Health.

REF 12

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 13

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 14

ClinicalTrials.gov (NCT04186871) A Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Assess the Efficacy and Safety of Branebrutinib Treatment in Subjects With Active Systemic Lupus Erythematosus or Primary Sj?gren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Subjects With Active Rheumatoid Arthritis. U.S.National Institutes of Health.

REF 15

Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans. J Pharmacol Exp Ther. 2013 Aug;346(2):219-28.

REF 16

ClinicalTrials.gov (NCT04305444) Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas. U.S. National Institutes of Health.

REF 17

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 18

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 19

ClinicalTrials.gov (NCT04992546) A Randomized, Intra-patient, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Topically Administered PRN473 (SAR444727) in Patients With Mild to Moderate Atopic Dermatitis. U.S.National Institutes of Health.

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040955)

REF 21

ClinicalTrials.gov (NCT04477291) A Study of CG-806 in Patients With Relapsed or Refractory Acute Myeloid Leukemia. U.S. National Institutes of Health.

REF 22

ClinicalTrials.gov (NCT05294731) A Phase 1, Open-Label, Dose-Escalation and Expansion Study of the Bruton Tyrosine Kinase Targeted Protein-Degrader BGB-16673 in Chinese Patients With B-Cell Malignancies. U.S.National Institutes of Health.

REF 23

ClinicalTrials.gov (NCT03943056) A Phase 1, Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB091, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Healthy Adult Participants. U.S.National Institutes of Health.

REF 24

ClinicalTrials.gov (NCT01765478) Safety,PK/PD, Food Effect Study of Orally Administered HM71224 in Healthy Adult Male Volunteers. U.S. National Institutes of Health.

REF 25

ClinicalTrials.gov (NCT05176691) A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL). U.S.National Institutes of Health.

REF 26

ClinicalTrials.gov (NCT04210219) A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia. U.S. National Institutes of Health.

REF 27

ClinicalTrials.gov (NCT04830137) A Phase 1, Dose Escalation, Safety and Tolerability Study of NX-2127, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies. U.S.National Institutes of Health.

REF 28

ClinicalTrials.gov (NCT05131022) A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies. U.S.National Institutes of Health.

REF 29

ClinicalTrials.gov (NCT01659255) Phase I Study of ONO-4059 Given as Monotherapy in Patients With Relapsed/Refractory NHL and CLL. U.S. National Institutes of Health.

REF 30

ClinicalTrials.gov (NCT03671590) Study of TG-1701, an Irreversible Bruton's Tyrosine Kinase Inhibitor, in Patients With B-Cell Malignancies. U.S. National Institutes of Health.

REF 31

ClinicalTrials.gov (NCT05683717) A Phase I, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies. U.S.National Institutes of Health.

REF 32

Pyrrolo[2,3-d]pyrimidines active as Btk inhibitors.Expert Opin Ther Pat. 2017 Dec;27(12):1305-1318.

REF 33

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029717)

REF 34

Antiarthritis effect of a novel Bruton's tyrosine kinase (BTK) inhibitor in rat collagen-induced arthritis and mechanism-based pharmacokinetic/pharmacodynamic modeling: relationships between inhibition of BTK phosphorylation and efficacy. J Pharmacol Exp Ther. 2011 Jul;338(1):154-63.

REF 35

REF 36

Targeting BTK in CLL: Beyond Ibrutinib. Curr Hematol Malig Rep. 2019 Jun;14(3):197-205.

REF 37

Clinical pipeline report, company report or official report of InnoCare Pharma.

REF 38

Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2021 Sep;20(9):729-738.

REF 39

Safety, pharmacokinetics and pharmacodynamics of branebrutinib (BMS-986195), a covalent, irreversible inhibitor of Bruton's tyrosine kinase: Randomised phase I, placebo-controlled trial in healthy participants. Br J Clin Pharmacol. 2020 Sep;86(9):1849-1859.

REF 40

Preclinical Mechanisms of Topical PRN473, a Bruton Tyrosine Kinase Inhibitor, in Immune-Mediated Skin Disease Models. Immunohorizons. 2021 Jul 29;5(7):581-589.

REF 41

Clinical pipeline report, company report or official report of Aptose Biosciences.

REF 42

Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis. J Med Chem. 2022 Jan 27;65(2):1206-1224.

REF 43

ClinicalTrials.gov (NCT02900716) Safety Study of BTK Inhibitor, DTRMWXHS-12, Used Singly or in Combination, in CLL and B-cell Lymphomas. U.S. National Institutes of Health.

REF 44

HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211.

REF 45

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

REF 46

The Evolution of Therapies Targeting Bruton Tyrosine Kinase for the Treatment of Chronic Lymphocytic Leukaemia: Future Perspectives. Cancers (Basel). 2023 May 3;15(9):2596.

REF 47

ONO-4059, a novel oral Bruton's tyrosine kinase (Btk) inhibitor that demonstrates potent pharmacodynamic activity through Phosphorylated Btk (P-Btk) inhibition, in addition to effective anti-tumour activity in a TMD-8 (DLBCL) xenograft model. Cancer Research. 08/2013; 73(8 Supplement):2452-2452.

REF 48

Clinical pipeline report, company report or official report of TG Therapeutics.

REF 49

Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.

REF 50

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 October 10; 122(15): 2539-2549.

REF 51

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 52

A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.

REF 53

Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett. 2012 Jul 26;3(9):705-9.

REF 54

Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28.

REF 55

RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103.

REF 56

Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases. Protein Sci. 2010 Mar;19(3):429-39.

REF 57

Ability of Bruton's Tyrosine Kinase Inhibitors to Sequester Y551 and Prevent Phosphorylation Determines Potency for Inhibition of Fc Receptor but not B-Cell Receptor Signaling. Mol Pharmacol. 2017 Mar;91(3):208-219.

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