Target Information

Target General Information

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Target ID

T34624 (Former ID: TTDR00365)

Target Name

Stress-activated protein kinase (p38)

Synonyms

p38) Stress-activated protein kinase; P38 MAPK; P38 MAP kinase; Mitogen-activated protein kinase p38

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Gene Name

NO-GeName

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Cardiomyopathy [ICD-11: BC43]

BioChemical Class

Kinase

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 9 Clinical Trial Drugs

PF-07265803

Drug Info

Phase 3

Dilated cardiomyopathy

[2]

ARRY-797

Drug Info

Phase 2

Pain

[3]

AZD7624

Drug Info

Phase 2

Chronic obstructive pulmonary disease

[4]

BMS-582949

Drug Info

Phase 2

Psoriasis vulgaris

[5], [6]

GSK2269557

Drug Info

Phase 2

Asthma

[7]

MW150

Drug Info

Phase 2

Alzheimer disease

[8]

TAK-715

Drug Info

Phase 2

Rheumatoid arthritis

[9]

LY-2228820

Drug Info

Phase 1/2

Solid tumour/cancer

[10], [11]

PUR1800

Drug Info

Phase 1

Chronic obstructive pulmonary disease

[12]

Discontinued Drug(s)

[+] 6 Discontinued Drugs

ARRY-614

Drug Info

Discontinued in Phase 1

Myelodysplastic syndrome

[13]

AVE-9940

Drug Info

Discontinued in Phase 1

Rheumatoid arthritis

[14]

AZD-6703

Drug Info

Discontinued in Phase 1

Rheumatoid arthritis

[15], [16]

SB-281832

Drug Info

Discontinued in Phase 1

Asthma

[17]

TA-5493

Drug Info

Discontinued in Phase 1

Inflammation

[18]

AMG-548

Drug Info

Terminated

Inflammation

[19]

Mode of Action

[+] 3 Modes of Action

Antagonist

[+] 1 Antagonist drugs

PF-07265803

Drug Info

[20]

Inhibitor

[+] 13 Inhibitor drugs

ARRY-797

Drug Info

[21]

AZD7624

Drug Info

[1]

BMS-582949

Drug Info

[22]

GSK2269557

Drug Info

[23]

MW150

Drug Info

[24]

TAK-715

Drug Info

[25]

LY-2228820

Drug Info

[10]

PUR1800

Drug Info

[26]

AVE-9940

Drug Info

[28]

AZD-6703

Drug Info

[29]

SB-281832

Drug Info

[30]

TA-5493

Drug Info

[31]

AMG-548

Drug Info

[32]

Modulator

[+] 1 Modulator drugs

ARRY-614

Drug Info

[27]

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

References

Top

REF 1

Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92.

REF 2

ClinicalTrials.gov (NCT03439514) A Phase 3, Multinational, Randomized, Placebo-controlled Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation (REALM-DCM). U.S.National Institutes of Health.

REF 3

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019505)

REF 4

ClinicalTrials.gov (NCT02238483) A Phase IIa Study to Investigate the Efficacy and Safety of AZD7624 in Chronic Obstructive Pulmonary Disease (COPD) Patients While on Maintenance Therapy. U.S. National Institutes of Health.

REF 5

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: 7838).

REF 6

ClinicalTrials.gov (NCT00605735) PoC in Rheumatoid Arthritis With Methotrexate. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT02522299) A Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 in Chronic Obstructive Pulmonary Disease (COPD) Subjects With Acute Exacerbation.

REF 8

ClinicalTrials.gov (NCT05194163) A Phase 2a Study of MW150 Stress Kinase Inhibitor in Mild to Moderate Alzheimer's Disease. U.S.National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT00760864) Safety and Efficacy of TAK-715 in Subjects With Rheumatoid Arthritis. U.S. National Institutes of Health.

REF 10

REF 11

ClinicalTrials.gov (NCT01663857) A Study of LY2228820 for Recurrent Ovarian Cancer. U.S. National Institutes of Health.

REF 12

ClinicalTrials.gov (NCT04759807) A Phase 1b 3-way Crossover Study to Assess the Safety, Tolerability and Pharmacokinetics of Repeated Once Daily Doses of PUR1800 in Adult Patients With Stable Chronic Obstructive Pulmonary Disease. U.S.National Institutes of Health.

REF 13

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026289)

REF 14

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023206)

REF 15

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021256)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016500)

REF 18

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022792)

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019881)

REF 20

Clinical pipeline report, company report or official report of Pfizer

REF 21

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

REF 22

Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38alpha inhibitor. Bioorg Med Chem Lett. 2013 May 15;23(10):3028-33.

REF 23

Evaluation of WO2012032067 and WO2012055846: two selective PI3Kdelta inhibitors, which is GSK-2269557. Expert Opin Ther Pat. 2012 Aug;22(8):965-70.

REF 24

p38alpha MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10245-E10254.

REF 25

Inhibition of Wnt/beta-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Idelta/ . Chem Biol. 2011 Apr 22;18(4):485-94.

REF 26

Clinical pipeline report, company report or official report of Pulmatrix Lexington, MA

REF 27

Cmpany report (Arraybiopharma)

REF 28

US patent application no. 2008,0119,498, Therapeutic agent for pruritus comprising p38 map kinase inhibitor as the active ingredient.

REF 29

The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83.

REF 30

p38 MAPK inhibitors ameliorate target organ damage in hypertension: Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension. J Pharmacol Exp Ther. 2003 Dec;307(3):932-8.

REF 31

US patent application no. 2008,0269,123, Methods for treating polycystic kidney disease (pkd) or other cyst forming diseases.

REF 32

p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Devel. 2005 Jul;8(4):421-30.

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