Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3C80U)

• DTT Name: T-cell-specific kinase (ITK)
• Synonyms: Tyrosine kinase ITK; Inducible T cell kinase; EMT
• Gene Name: ITK
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: ITK_HUMAN
• TTD ID: T91761
• EC Number: EC 2.7.10.2
• Sequence:
  MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRI
  KCVEIVKSDISIPCHYKYPFQVVHDNYLLYVFAPDRESRQRWVLALKEETRNNNSLVPKY
  HPNFWMDGKWRCCSQLEKLATGCAQYDPTKNASKKPLPPTPEDNRRPLWEPEETVVIALY
  DYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEKSPNNLETYEWY
  NKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCIKHYHIKETND
  NPKRYYVAEKYVFDSIPLLINYHQHNGGGLVTRLRYPVCFGRQKAPVTAGLRYGKWVIDP
  SELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQ
  LYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIH
  RDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSD
  VWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE
  DRPAFSRLLRQLAEIAESGL
• Function: Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3. Tyrosine kinase that plays an essential role in regulation of the adaptive immune response.
• KEGG Pathway:
  Chemokine signaling pathway (hsa04062)
  T cell receptor signaling pathway (hsa04660)
  Leukocyte transendothelial migration (hsa04670)
• Reactome Pathway:
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  Generation of second messenger molecules (R-HSA-202433)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JTE-051	DM2LBHN	Plaque psoriasis	EA90.0	Phase 2	[1]
CPI-818	DMMBQ20	T-cell lymphoma	2A90	Phase 1	[2]

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27774824-Compound-Figure3Example7	DMXDOGK	N. A.	N. A.	Patented	[3]
Pyrazolo[4,3-c]pyridine derivative 2	DMCDFLQ	N. A.	N. A.	Patented	[3]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-488516	DM6Y1QF	Inflammation	1A00-CA43.1	Investigative	[4]
BMS-509744	DMGH1LX	Inflammation	1A00-CA43.1	Investigative	[4]

References

• [1] Characterisation of a K390R ITK Kinase Dead Transgenic Mouse - Implications for ITK as a Therapeutic Target. PLoS One. 2014; 9(9): e107490.
• [2] Clinical pipeline report, company report or official report of Corvus Pharmaceuticals.
• [3] 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.
• [4] Treatment of depersonalization with serotonin reuptake blockers. J Clin Psychopharmacol. 1990 Jun;10(3):200-3.