Target Information

Target General Information

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Target ID

T04820 (Former ID: TTDR00301)

Target Name

Plasmodium CDK Pfmrk (Malaria Pfmrk)

Synonyms

Pfmrk; MO15-related protein kinase Pfmrk

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Gene Name

Malaria Pfmrk

Target Type

Patented-recorded target

[1]

Disease

[+] 1 Target-related Diseases

Malaria [ICD-11: 1F40-1F45]

Function

Association of Pfmrk with human cyclin H (the cyclin partner for hCDK7) or Pfcyc-1 (a cyclin homologue in P. falciparum) stimulates kinase activity in vitro.

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BioChemical Class

Kinase

UniProt ID

P90584_PLAFA

EC Number

EC 2.7.1.37

Sequence

MENNSTERYIFKPNFLGEGSYGKVYKAYDTILKKEVAIKKMKLNEISNYIDDCGINFVLL
REIKIMKEIKHKNIMSALDLYCEKDYINLVMEIMDYDLSKIINRKIFLTDSQKKCILLQI
LNGLNVLHKYYFMHRDLSPANIFINKKGEVKLADFGLCTKYGYDMYSDKLFRDKYKKNLN
LTSKVVTLWYRAPELLLGSNKYNSSIDMWSFGCIFAELLLQKALFPGENEIDQLGKIFFL
LGTPNENNWPEALCLPLYTEFTKATKKDFKTYFKIDDDDCIDLLTSFLKLNAHERISAED
AMKHRYFFNDPLPCDISQLPFNDL

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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 Similarity Proteins

Different Human System Profiles of Target

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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 Similarity Proteins

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Renal carcinoma antigen NY-REN-64 (IRAK-4)	PF07714	29.004 (67/231)	1.27E-16
Janus kinase 1 (JAK-1)	PF18379 ; PF18377 ; PF17887 ; PF07714 More >>	30.973 (70/226)	1.45E-16
Receptor-interacting protein 1 (RIPK1)	PF00531 ; PF07714 ; PF12721 More >>	31.319 (57/182)	3.52E-14
Tyrosine-protein kinase ABL1 (ABL)	PF08919 ; PF07714 ; PF00017 ; PF00018 More >>	29.384 (62/211)	5.26E-14
Tyrosine-protein kinase FRK (FRK)	PF07714 ; PF00017 ; PF00018 More >>	26.190 (55/210)	1.02E-13
Tyrosine-protein kinase ABL2 (ABL2)	PF08919 ; PF07714 ; PF00017 ; PF00018 More >>	29.119 (76/261)	1.74E-13
Discoidin domain-containing receptor 2 (DDR2)	PF00754 ; PF07714	26.638 (61/229)	3.39E-13
Proto-oncogene c-RAF (c-RAF)	PF00130 ; PF07714 ; PF02196 More >>	23.045 (56/243)	1.14E-12
Proto-oncogene c-Met (MET)	PF07714 ; PF01437 ; PF01403 ; PF01833 More >>	30.131 (69/229)	1.29E-12
BDNF/NT-3 growth factors receptor (TrkB)	PF07679 ; PF13855 ; PF16920 ; PF01462 ; PF07714 More >>	27.354 (61/223)	1.82E-12
Ephrin type-A receptor 1 (EPHA1)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	25.837 (54/209)	4.02E-12
Neurotrophic tyrosine kinase ROR1 (ROR1)	PF01392 ; PF07679 ; PF00051 ; PF07714 More >>	25.551 (58/227)	4.81E-12
Muscle-specific kinase receptor (MUSK)	PF01392 ; PF07679 ; PF13927 ; PF07714 More >>	25.751 (60/233)	5.39E-12
Tyrosine-protein kinase BRK (PTK6)	PF07714 ; PF00017 ; PF00018 More >>	26.027 (57/219)	6.90E-12
TYK2 tyrosine kinase (TYK2)	PF18379 ; PF18377 ; PF17887 ; PF07714 More >>	30.000 (69/230)	8.91E-12
Ephrin type-B receptor 1 (EPHB1)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	28.302 (60/212)	1.07E-11
Janus kinase 2 (JAK-2)	PF18379 ; PF18377 ; PF17887 ; PF07714 ; PF00017 More >>	28.571 (64/224)	1.37E-11
Tyrosine-protein kinase UFO (AXL)	PF00041 ; PF13927 ; PF07714 More >>	27.155 (63/232)	1.64E-11
Tyrosine-protein kinase ZAP-70 (ZAP-70)	PF07714 ; PF00017	27.404 (57/208)	1.66E-11
Testis-specific kinase 1 (TESK1)	PF07714	22.857 (48/210)	2.12E-11
Tyrosine-protein kinase SYK (SYK)	PF07714 ; PF00017	27.586 (56/203)	3.03E-11
LIM domain kinase-2 (LIMK-2)	PF00412 ; PF00595 ; PF07714 More >>	24.786 (58/234)	3.39E-11
Serine/threonine-protein kinase B-raf (BRAF)	PF00130 ; PF07714 ; PF02196 More >>	25.424 (60/236)	4.10E-11
LIM domain kinase-1 (LIMK-1)	PF00412 ; PF00595 ; PF07714 More >>	25.114 (55/219)	4.31E-11
NT-3 growth factor receptor (TrkC)	PF07679 ; PF00047 ; PF13855 ; PF16920 ; PF01462 ; PF07714 More >>	25.862 (60/232)	5.06E-11
Ephrin type-A receptor 2 (EPHA2)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	26.389 (57/216)	5.18E-11
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13)	PF07714	27.830 (59/212)	5.66E-11
Tropomyosin-related kinase A (TrkA)	PF13855 ; PF16920 ; PF07714 ; PF18613 More >>	25.893 (58/224)	5.85E-11
Proto-oncogene c-Fer (FER)	PF00611 ; PF07714 ; PF00017 More >>	27.189 (59/217)	6.24E-11
Fibroblast growth factor receptor 2 (FGFR2)	PF07679 ; PF13927 ; PF07714 More >>	26.667 (64/240)	7.74E-11
Fyn tyrosine protein kinase (FYN)	PF07714 ; PF00017 ; PF00018 More >>	26.840 (62/231)	1.04E-10
Mixed lineage kinase 2 (MAP3K10)	PF07714 ; PF14604	25.532 (60/235)	1.17E-10
Yes tyrosine kinase (YES)	PF07714 ; PF00017 ; PF00018 More >>	26.749 (65/243)	1.24E-10
Tyrosine-protein kinase Fgr (FGR)	PF07714 ; PF00017 ; PF00018 More >>	25.862 (60/232)	1.27E-10
Proto-oncogene c-Src (SRC)	PF07714 ; PF00017 ; PF00018 More >>	26.423 (65/246)	1.39E-10
Fibroblast growth factor receptor 1 (FGFR1)	PF07679 ; PF00047 ; PF07714 More >>	26.891 (64/238)	1.62E-10
Fibroblast growth factor receptor 4 (FGFR4)	PF07679 ; PF13927 ; PF07714 More >>	23.851 (83/348)	2.26E-10
Tyrosine-protein kinase Srms (SRMS)	PF07714 ; PF00017	25.118 (53/211)	2.49E-10
Fibroblast growth factor receptor 3 (FGFR3)	PF07679 ; PF13927 ; PF07714 More >>	26.891 (64/238)	2.76E-10
Epithelial discoidin domain receptor 1 (DDR1)	PF00754 ; PF07714	22.407 (54/241)	3.00E-10
Mitogen-activated protein kinase kinase kinase 12 (MAP3K12)	PF07714	26.442 (55/208)	3.34E-10
T-cell-specific kinase (ITK)	PF00779 ; PF00169 ; PF07714 ; PF00017 ; PF00018 More >>	25.806 (56/217)	3.56E-10
Serine/threonine-protein kinase A-Raf (ARAF)	PF00130 ; PF07714 ; PF02196 More >>	20.661 (50/242)	4.78E-10
Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1)	PF12796 ; PF13637 ; PF07714 More >>	29.091 (64/220)	5.24E-10
Proto-oncogene c-Ros (ROS1)	PF00041 ; PF07714	27.126 (67/247)	7.88E-10
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	PF00619 ; PF07714	26.027 (57/219)	1.11E-09
Proto-oncogene c-Fes (FES)	PF07714 ; PF00017	24.880 (52/209)	1.19E-09
LCK tyrosine protein kinase (LCK)	PF07714 ; PF00017 ; PF00018 More >>	26.267 (57/217)	1.57E-09
Ephrin type-B receptor 2 (EPHB2)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	26.887 (57/212)	1.74E-09
Ephrin type-B receptor 3 (EPHB3)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	26.512 (57/215)	1.93E-09
Proto-oncogene c-Ret (RET)	PF00028 ; PF07714 ; PF17756 ; PF17812 ; PF17813 More >>	26.000 (65/250)	1.99E-09
Tyrosine-protein kinase Lyn (JTK8)	PF07714 ; PF00017 ; PF00018 More >>	25.000 (62/248)	2.00E-09
Megakaryocyte-associated tyrosine-protein kinase (MATK)	PF07714 ; PF00017 ; PF00018 More >>	23.415 (48/205)	2.14E-09
Testis-specific kinase 2 (TESK2)	PF07714	24.645 (52/211)	2.36E-09
Ephrin type-B receptor 4 (EPHB4)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	26.941 (59/219)	3.06E-09
Tyrosine-protein kinase TXK (TXK)	PF07714 ; PF00017 ; PF00018 More >>	26.852 (58/216)	3.14E-09
Tyrosine-protein kinase Tec (PSCTK4)	PF00779 ; PF00169 ; PF07714 ; PF00017 ; PF00018 More >>	23.223 (49/211)	3.15E-09
Hematopoietic cell kinase (HCK)	PF07714 ; PF00017 ; PF00018 More >>	27.016 (67/248)	3.96E-09
Inactive tyrosine-protein kinase 7 (PTK7)	PF07679 ; PF13927 ; PF07714 More >>	22.271 (51/229)	4.07E-09
Tyrosine-protein kinase BTK (ATK)	PF00779 ; PF00169 ; PF07714 ; PF00017 ; PF00018 More >>	27.143 (57/210)	4.51E-09
Serine/threonine-protein kinase TNNI3K (TNNI3K)	PF12796 ; PF13637 ; PF07714 More >>	24.885 (54/217)	5.15E-09
Dual serine/threonine and tyrosine protein kinase (DSTYK)	PF07714	25.604 (53/207)	7.99E-09
Vascular endothelial growth factor receptor 2 (KDR)	PF07679 ; PF13927 ; PF07714 ; PF17988 More >>	32.258 (40/124)	1.04E-08
Insulin-like growth factor I receptor (IGF1R)	PF00757 ; PF07714 ; PF01030 More >>	26.941 (59/219)	1.12E-08
Non-receptor tyrosine-protein kinase TNK1 (TNK1)	PF07714	22.523 (50/222)	1.36E-08
Leukocyte receptor tyrosine kinase (LTK)	PF12810 ; PF07714	24.201 (53/219)	1.54E-08
MLK-related kinase (MLTK)	PF07714 ; PF00536	24.545 (54/220)	1.58E-08
Macrophage-stimulating protein receptor (RON)	PF07714 ; PF01403 ; PF01833 More >>	25.847 (61/236)	1.79E-08
Ephrin type-A receptor 5 (EPHA5)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	25.472 (54/212)	1.86E-08
Ephrin type-A receptor 3 (EPHA3)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF07647 More >>	25.000 (53/212)	1.97E-08
Janus kinase 3 (JAK-3)	PF18379 ; PF18377 ; PF17887 ; PF07714 More >>	28.251 (63/223)	2.49E-08
Tyrosine-protein kinase CSK (CSK)	PF07714 ; PF00017 ; PF00018 More >>	26.901 (46/171)	3.56E-08
Ephrin type-A receptor 4 (EPHA4)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF07647 More >>	22.897 (49/214)	4.68E-08
Ephrin type-A receptor 7 (EPHA7)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	25.000 (53/212)	4.91E-08
Mixed lineage kinase 3 (MAP3K11)	PF07714 ; PF14604	25.225 (56/222)	6.98E-08
TGF-beta-activated kinase 1 (MAP3K7)	PF07714	24.686 (59/239)	7.82E-08
Bone morphogenetic protein receptor type-1B (BMPR1B)	PF01064 ; PF07714 ; PF08515 More >>	25.743 (78/303)	9.37E-08
TYRO3 tyrosine kinase receptor (TYRO3)	PF00041 ; PF07679 ; PF07714 More >>	26.754 (61/228)	1.43E-07
Platelet-derived growth factor receptor beta (PDGFRB)	PF07679 ; PF00047 ; PF13927 ; PF07714 More >>	29.605 (45/152)	1.69E-07
Insulin receptor (INSR)	PF00757 ; PF17870 ; PF07714 ; PF01030 More >>	27.397 (60/219)	1.75E-07
Activin receptor-like kinase 2 (ALK-2)	PF01064 ; PF07714 ; PF08515 More >>	24.786 (58/234)	1.78E-07
Focal adhesion kinase 2 (PTK2B)	PF00373 ; PF18038 ; PF03623 ; PF07714 More >>	28.037 (60/214)	2.09E-07
Vascular endothelial growth factor receptor 3 (FLT-4)	PF07679 ; PF13927 ; PF07714 ; PF17988 More >>	30.579 (37/121)	2.18E-07
Focal adhesion kinase 1 (FAK)	PF00373 ; PF18038 ; PF03623 ; PF07714 More >>	24.219 (62/256)	2.21E-07
Epidermal growth factor receptor (EGFR)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	24.766 (53/214)	2.28E-07
Tyrosine-protein kinase Mer (MERTK)	PF00041 ; PF00047 ; PF07714 More >>	27.477 (61/222)	2.38E-07
Neurotrophic tyrosine kinase ROR2 (ROR2)	PF01392 ; PF07679 ; PF00051 ; PF07714 More >>	20.264 (46/227)	3.70E-07
Erbb2 tyrosine kinase receptor (HER2)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	24.658 (54/219)	3.73E-07
Insulin receptor-related protein (INSRR)	PF00757 ; PF07714 ; PF01030 More >>	25.909 (57/220)	4.29E-07
Angiopoietin 1 receptor (TEK)	PF00041 ; PF10430 ; PF07714 More >>	23.348 (53/227)	4.53E-07
Erbb4 tyrosine kinase receptor (Erbb-4)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	25.714 (54/210)	4.94E-07
Bone morphogenetic protein receptor type-1A (BMPR1A)	PF01064 ; PF07714 ; PF08515 More >>	24.615 (64/260)	5.74E-07
Titin (TTN)		24.312 (53/218)	6.16E-07
B lymphocyte kinase (BLK)	PF07714 ; PF00017 ; PF00018 More >>	25.909 (57/220)	7.12E-07
Activated CDC42 kinase 1 (ACK-1)	PF09027 ; PF11555 ; PF07714 ; PF14604 More >>	25.000 (54/216)	7.87E-07
Tyrosine-protein kinase BMX (BMX)	PF00779 ; PF00169 ; PF07714 ; PF00017 More >>	26.570 (55/207)	8.21E-07
Serine/threonine-protein kinase LMTK2 (LMTK2)	PF07714	23.585 (75/318)	1.04E-06
Tie-1 tyrosine kinase receptor (TIE1)	PF00041 ; PF00047 ; PF07714 More >>	23.451 (53/226)	1.83E-06
Kinase suppressor of Ras 2 (KSR2)	PF07714 ; PF13543 ; PF20406 More >>	23.431 (56/239)	2.46E-06
Ephrin type-A receptor 6 (EPHA6)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	26.923 (28/104)	3.23E-06
Ephrin type-A receptor 8 (EPHA8)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	23.560 (45/191)	3.39E-06
Retinal guanylyl cyclase 2 (GUCY2F)	PF01094 ; PF00211 ; PF07701 ; PF07714 More >>	23.664 (62/262)	7.55E-06
Mixed lineage kinase 4 (MAP3K21)	PF07714 ; PF14604	21.757 (52/239)	1.37E-05
Vascular endothelial growth factor receptor 1 (FLT-1)	PF07679 ; PF00047 ; PF13927 ; PF07714 ; PF17988 More >>	28.829 (32/111)	1.58E-05
Kinase suppressor of Ras-1 (KSR1)	PF07714 ; PF13543 ; PF20406 More >>	23.256 (50/215)	1.69E-05
ALK tyrosine kinase receptor (ALK)	PF12810 ; PF00629 ; PF07714 More >>	22.727 (50/220)	4.06E-05
Tyrosine-protein kinase RYK (RYK)	PF07714 ; PF02019	22.222 (50/225)	7.53E-05
Erbb3 tyrosine kinase receptor (Erbb-3)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	28.431 (29/102)	1.48E-04
Tyrosine-protein kinase STYK1 (STYK1)	PF07714	23.982 (53/221)	1.68E-04
Serine/threonine-protein kinase LMTK1 (AATK)	PF07714	24.887 (55/221)	3.20E-04
Platelet-derived growth factor receptor alpha (PDGFRA)	PF07679 ; PF07714	28.182 (31/110)	4.04E-04
Fms-like tyrosine kinase 3 (FLT-3)	PF00047 ; PF07714	29.825 (34/114)	4.05E-04
Activin receptor type-1C (ACVR1C)	PF01064 ; PF07714 ; PF08515 More >>	22.807 (65/285)	5.05E-04
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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

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

A three-dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclin-dependent kinases and discovery of different class... J Med Chem. 2004 Oct 21;47(22):5418-26.

REF 2

Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases, Bioorg. Med. Chem. Lett. 20(13):3863-3867 (2010).

REF 3

Evaluation of broad spectrum protein kinase inhibitors to probe the architecture of the malarial cyclin dependent protein kinase Pfmrk. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4961-6.

REF 4

Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.

REF 5

Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.

REF 6

Selective inhibition of Pfmrk, a Plasmodium falciparum CDK, by antimalarial 1,3-diaryl-2-propenones. Bioorg Med Chem Lett. 2009 Apr 1;19(7):1982-5.

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