Target Information
Target General Information | Top | |||||
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Target ID |
T31406
(Former ID: TTDI03254)
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Target Name |
Hematopoietic cell kinase (HCK)
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Synonyms |
p61Hck; p59Hck; p59-HCK/p60-HCK; Tyrosine-protein kinase HCK; Hemopoietic cell kinase
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Gene Name |
HCK
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Target Type |
Patented-recorded target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Indeterminate colitis [ICD-11: DD72] | |||||
Function |
Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration.
Click to Show/Hide
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BioChemical Class |
Kinase
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UniProt ID | ||||||
EC Number |
EC 2.7.10.2
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Sequence |
MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIK
PGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSL ATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSY SLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVP CMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVE AFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLID FSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFP IKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPE NCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
Drugs and Modes of Action | Top | |||||
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Patented Agent(s) | [+] 1 Patented Agents | + | ||||
1 | Doramapimod | Drug Info | Discontinued in Phase 2 | Inflammatory bowel disease | [2], [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 11 Inhibitor drugs | + | ||||
1 | 3-(6-allyloxy-2-naphthyl)-1-(4-piperidylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine | Drug Info | [4] | |||
2 | BK3 | Drug Info | [4] | |||
3 | BK7 | Drug Info | [4] | |||
4 | Doramapimod | Drug Info | [5] | |||
5 | SB19065 | Drug Info | [6] | |||
6 | Unii-I92MU0V408 | Drug Info | [5] | |||
7 | US8933228, 3 | Drug Info | [5] | |||
8 | US8933228, Ref 2 | Drug Info | [7] | |||
9 | US9108950, 1 | Drug Info | [8] | |||
10 | PMID15546730C2 | Drug Info | [9] | |||
11 | PP121 | Drug Info | [1] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"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 | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-interacting Proteins |
References | Top | |||||
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REF 1 | Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9. | |||||
REF 2 | 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: 5668). | |||||
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 800017152) | |||||
REF 4 | Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases. US9765037. | |||||
REF 5 | Respiratory formulations and compounds for use therein. US8933228. | |||||
REF 6 | Anti-inflammatory compound having inhibitory activity against multiple tyrosine kinases and pharmaceutical composition containing same. US9062066. | |||||
REF 7 | 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as P38 MAP knase inhibitors. US9724347. | |||||
REF 8 | 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as p38 MAP kinase inhibitors. US9108950. | |||||
REF 9 | Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6061-6. |
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