itk inhibitor

Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. ITK inhibitors can be used for the treatment of inflammation and immune-mediated disorders. ITK inhibitor (N-[5-[[3-[(4-Acetylpiperazin-1-yl)carbonyl]-4-methyl-6-methoxy-phenyl]thio]thiazol-2-yl]-4-(N-1,2-dimethylpropylaminomethyl)benzamide) is the analogue of BMS-509744, which can potently and selectively inhibit Itk kinase activity. In vitro: BMS-509744 could reduce TCR-induced functions including PLCγ1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion, and T-cell proliferation in vitro in both human and mouse cells [1]. In vivo: BMS-509744 suppressed the production of IL-2 induced by anti-TCR antibody administered to mice. BMS-509744 also significantly diminishes lung inflammation in a mouse model of ovalbumin-induced allergy/asthma [1]. Clinical trial: Up to now, both BMS-509744 and ITK inhibitor is still in the preclinical development stage.

ITK inhibitor 2 (compound 4) is a potent and selective ITK inhibitor with an IC50= 2 nM.

ITK inhibitor 5 (compound 27) is a highly potent and selective ITK inhibitor, demonstrating IC50 values of 5.6 nM for ITK and 25 nM for BTK [1].

ITK inhibitor 6 is a selective and potent ITK inhibitor that acts on ITK (IC50: 4 nM), BTK (IC50: 133 nM), JAK3 (IC50: 320 nM), EGFR (IC50: 2360 nM), LCK (IC50: 155 nM). ITK inhibitor 6 inhibited the phosphorylation of PLCγ1 and ERK1 2 and showed anti-proliferative effect.

Vecabrutinib (SNS-062) is a potent, noncovalent inhibitor of BTK (Kd: 0.3 nM) and ITK (Kd: 2.2 nM), with an IC50 of 24 nM for ITK.

Rilzabrutinib (PRN1008) is a reversible covalent, selective, and orally active inhibitor of Bruton's Tyrosine Kinase (BTK) with an IC50 of 1.3 nM.

BMS-509744 is an inhibitor of ATP competitive Itk (IC50: 19 nM).

BMX-IN-1 (BMX kinase inhibitor) is a selective inhibitor of bone marrow tyrosine kinase on chromosome X (BMX, IC50 = 8 nM) and the related Bruton's tyrosine kinase (BTK, IC50 = 10.4 nM), but BMX-IN-1 is more than 47-656 fold less potent against Blk, JAK3, EGFR, Itk, or Tec activity.

PF-06465469 is a covalent ITK inhibitor(IC50: 2 nM).

PRN694 shows extended target residence time on ITK and RLK, enabling durable attenuation of effector cells in vitro and in vivo. PRN694 is an irreversible, highly selective, and effective covalent interleukin-2-inducible T-cell kinase (ITK) and resting ly

GSK-2250665A is a Itk inhibitor with pKi value of 9.2.

GNE-9822 is a potent selective ITK inhibitor that shows favorable ADME properties in preclinical species.

CTA 056 is an interleukin-2 induced T cell kinase (ITK) inhibitor, inhibits the growth of MOLT-4 xenograft tumors in mice, induces apoptosis in Jurkat cells, and can be used in the study of autoimmune disorders and T cell malignancies.

BMS-986143, an orally active, reversible BTK inhibitor with an IC50 value of 0.26 nM, is designed for autoimmune disease research. Additionally, it targets TEC, BLK, BMX, TXK, FGR, YES1, and ITK, exhibiting IC50s of 3 nM, 5 nM, 7 nM, 10 nM, 15 nM, 19 nM, and 21 nM, respectively [1].

ITK TRKA-IN-1 is a chemical compound that functions as a dual inhibitor of IL-2-inducible T-cell kinase (ITK) and tropomyosin receptor kinase A (TRKA). With an IC50 value of 1.0 nM, it effectively inhibits ITK activity and demonstrates a remarkable 96% inhibition of TRKA.

BAY 61-3606 (Syk inhibitor IV) is a potent, ATP-competitive, reversible, and highly selective inhibitor of Syk tyrosine kinase activity (Ki= 7.5 nM), exhibiting no inhibitory effect against Btk, Fyn, Itk, Lyn, and Src.

PCI 29732 is a selective and irreversible Btk inhibitor with IC50 of 8.2 nM in a FRET based biochemical enzymology assay.

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase that, upon phosphorylation, binds to immunoreceptor tyrosine-based activation motifs of FcRγ chains and mediates downstream signaling related to platelet function and inflammation. Syk inhibit

EGFR-IN-40 (compound 3z) is a potent inhibitor of BTK (IC50: 1.2 nM), EGFR (IC50: 5.3 nM), and ITK (IC50: 46.1 nM).

BTK-IN-7 is a selective and potent BTK inhibitor with an IC50 value of 4.0 nM. BTK-IN-7 exhibits high selectivity at both the enzymatic (ITK>250-fold, EGFR>2500-fold) and cellular levels (ITK>227-fold, EGFR27-fold). BTK-IN-7 exhibits high high antitumor effect.

J-31 is an inactive conformation inhibitor of ITK.

PARP11 Inhibitor ITK7 (ITK7) is a potent, selective inhibitor of PARP11, demonstrating significant efficacy with an IC50 value of 14 nM. It is primarily utilized in research focused on cellular localization.

Soquelitinib (CPI-818) is a covalent, irreversible, oral and selective ITK inhibitor that preferentially inhibits Th2 cytokine production over Th1, inhibits in vivo tumor growth in mice, and decreases markers of T-cell exhaustion, resulting in an increase in tumor infiltration and up-regulation of CXCR3, IFNγ, TNFα, and CD107a expression in normal CD8 cells.