Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTX6F0Q)

• DTT Name: Tyrosine-protein kinase CSK (CSK)
• Synonyms: Protein-tyrosine kinase CYL; C-Src kinase
• Gene Name: CSK
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: CSK_HUMAN
• TTD ID: T08741
• EC Number: EC 2.7.10.2
• Sequence:
  MSAIQAAWPSGTECIAKYNFHGTAEQDLPFCKGDVLTIVAVTKDPNWYKAKNKVGREGII
  PANYVQKREGVKAGTKLSLMPWFHGKITREQAERLLYPPETGLFLVRESTNYPGDYTLCV
  SCDGKVEHYRIMYHASKLSIDEEVYFENLMQLVEHYTSDADGLCTRLIKPKVMEGTVAAQ
  DEFYRSGWALNMKELKLLQTIGKGEFGDVMLGDYRGNKVAVKCIKNDATAQAFLAEASVM
  TQLRHSNLVQLLGVIVEEKGGLYIVTEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCE
  AMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQDTGKLPVKWTAPEALRE
  KKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYEVMK
  NCWHLDAAMRPSFLQLREQLEHIKTHELHL
• Function: Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN, CSK or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK. Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response.
• Reactome Pathway:
  Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427)
  Integrin signaling (R-HSA-354192)
  PD-1 signaling (R-HSA-389948)
  MAP2K and MAPK activation (R-HSA-5674135)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  RHOH GTPase cycle (R-HSA-9013407)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Negative regulation of FLT3 (R-HSA-9706369)
  GAB1 signalosome (R-HSA-180292)

Molecular Interaction Atlas (MIA) of This DTT

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
936563-93-8	DMPQ2L9	N. A.	N. A.	Patented	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NG-25	DMC48D9	Discovery agent	N.A.	Investigative	[1]

References

• [1] Discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem. 2015 Jan 8;58(1):183-96.
• [2] Inhibitors of bruton's tyrosine kinase for the treatment of solid tumors. US9278100.