Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT42OGM)

• DTT Name: Hematopoietic cell kinase (HCK)
• Synonyms: p61Hck; p59Hck; p59-HCK/p60-HCK; Tyrosine-protein kinase HCK; Hemopoietic cell kinase
• Gene Name: HCK
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: HCK_HUMAN
• TTD ID: T31406
• EC Number: EC 2.7.10.2
• Sequence:
  MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIK
  PGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSL
  ATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSY
  SLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVP
  CMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVE
  AFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLID
  FSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFP
  IKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPE
  NCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP
• 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.
• KEGG Pathway:
  Chemokine signaling pathway (hsa04062)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
• Reactome Pathway:
  FCGR activation (R-HSA-2029481)
  Regulation of signaling by CBL (R-HSA-912631)
  FCGR3A-mediated IL10 synthesis (R-HSA-9664323)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Signaling by CSF3 (G-CSF) (R-HSA-9674555)
  Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462)
  FLT3 signaling through SRC family kinases (R-HSA-9706374)
  Nef and signal transduction (R-HSA-164944)

Molecular Interaction Atlas (MIA) of This DTT

9 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-(6-allyloxy-2-naphthyl)-1-(4-piperidylmethyl)pyrazolo[3,4-d]pyrimidin-4-amine	DM0DYAU	N. A.	N. A.	Patented	[2]
BK3	DM6YQO3	N. A.	N. A.	Patented	[2]
BK7	DMQD4X2	N. A.	N. A.	Patented	[2]
Doramapimod	DM6BU7N	Inflammatory bowel disease	DD72	Patented	[3]
SB19065	DM2MQD0	N. A.	N. A.	Patented	[4]
Unii-I92MU0V408	DMUD7H8	N. A.	N. A.	Patented	[3]
US8933228, 3	DMPNCOL	N. A.	N. A.	Patented	[3]
US8933228, Ref 2	DMKEX51	N. A.	N. A.	Patented	[5]
US9108950, 1	DMPT2ZS	N. A.	N. A.	Patented	[6]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID15546730C2	DMOPUIH	Discovery agent	N.A.	Investigative	[7]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[1]

References

• [1] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [2] Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases. US9765037.
• [3] Respiratory formulations and compounds for use therein. US8933228.
• [4] Anti-inflammatory compound having inhibitory activity against multiple tyrosine kinases and pharmaceutical composition containing same. US9062066.
• [5] 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as P38 MAP knase inhibitors. US9724347.
• [6] 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as p38 MAP kinase inhibitors. US9108950.
• [7] 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.