Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNDSC3)

• DTT Name: B lymphocyte kinase (BLK)
• Synonyms: p55-Blk; Tyrosine-protein kinase Blk
• Gene Name: BLK
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: BLK_HUMAN
• TTD ID: T74307
• EC Number: EC 2.7.10.2
• Sequence:
  MGLVSSKKPDKEKPIKEKDKGQWSPLKVSAQDKDAPPLPPLVVFNHLTPPPPDEHLDEDK
  HFVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVARVESLE
  MERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQGELIKHYKIR
  CLDEGGYYISPRITFPSLQALVQHYSKKGDGLCQRLTLPCVRPAPQNPWAQDEWEIPRQS
  LRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY
  AVVTKEPIYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRD
  LRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWS
  FGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRGVIAECWRSRPEER
  PTFEFLQSVLEDFYTATERQYELQP
• Function: B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. Phosphorylates CGAS, promoting retention of CGAS in the cytosol. Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
• Reactome Pathway:
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  RUNX1 regulates transcription of genes involved in BCR signaling (R-HSA-8939245)

Molecular Interaction Atlas (MIA) of This DTT

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pyrazolo[4,3-c]pyridine derivative 2	DMCDFLQ	N. A.	N. A.	Patented	[1]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID15546730C2	DMOPUIH	Discovery agent	N.A.	Investigative	[2]
PMID24915291C31	DMN7QB8	Discovery agent	N.A.	Investigative	[3]
PMID24915291C38	DMBXT9J	Discovery agent	N.A.	Investigative	[3]

References

• [1] 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.
• [2] 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.
• [3] 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.