Target General Infomation
Target ID
T91761
Former ID
TTDR00858
Target Name
Tyrosine-protein kinase itk/tsk
Gene Name
ITK
Synonyms
Inducible T cell kinase; Kinase EMT; T-cell-specific kinase; Tyrosine kinase ITK; Tyrosine-protein kinase Lyk; ITK
Target Type
Clinical Trial
Disease Allergy [ICD9: 995.3; ICD10: T78.4]
Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. 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.
BioChemical Class
Kinase
UniProt ID
EC Number
EC 2.7.10.2
Sequence
MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRI
KCVEIVKSDISIPCHYKYPFQVVHDNYLLYVFAPDRESRQRWVLALKEETRNNNSLVPKY
HPNFWMDGKWRCCSQLEKLATGCAQYDPTKNASKKPLPPTPEDNRRPLWEPEETVVIALY
DYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEKSPNNLETYEWY
NKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCIKHYHIKETND
NPKRYYVAEKYVFDSIPLLINYHQHNGGGLVTRLRYPVCFGRQKAPVTAGLRYGKWVIDP
SELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQ
LYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIH
RDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSD
VWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE
DRPAFSRLLRQLAEIAESGL
Drugs and Mode of Action
Drug(s) JTE-051 Drug Info Phase 1 Allergy [549363]
Inhibitor compound 4g Drug Info [531363]
compound 7 Drug Info [531860]
JTE-051 Drug Info [550352]
Pathways
KEGG Pathway Chemokine signaling pathway
T cell receptor signaling pathway
Leukocyte transendothelial migration
NetPath Pathway IL2 Signaling Pathway
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells
TCR signaling in na&amp
#xef
ve CD4+ T cells
Class I PI3K signaling events
Reactome Generation of second messenger molecules
FCERI mediated Ca+2 mobilization
WikiPathways TCR Signaling Pathway
T-Cell Receptor and Co-stimulatory Signaling
TCR signaling
References
Ref 549363Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035711)
Ref 531363Optimisation of ITK inhibitors through successive iterative design cycles. Bioorg Med Chem Lett. 2011 Mar 15;21(6):1852-6.
Ref 531860X-ray crystallographic structure-based design of selective thienopyrazole inhibitors for interleukin-2-inducible tyrosine kinase. Bioorg Med Chem Lett. 2012 May 1;22(9):3296-300.
Ref 550352Characterisation of a K390R ITK Kinase Dead Transgenic Mouse - Implications for ITK as a Therapeutic Target. PLoS One. 2014; 9(9): e107490.

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