BMS-509744

A cell-permeable aminothioaryl-thiazolo compound that potently inhibits ITK kinase activity (IC₅₀ = 19 nM; [ATP] = 1 M) in an ATP-competitive manner by stabilizing ITK activation loop in a substrate-blocking, inactive conformation, inhibiting Fyn, IR, Lck, Btk only at much higher concentrations (IC₅₀ = 1.1, 1.1, 2.4, and 4.1 M, respectively) and exhibiting little or no activity against 14 other kinases (IC₅₀ ≥11 M). Inhibits ITK-dependent, but not ITK-independent, PLCγ1 tyrosine phosphorylation (IC₅₀<300 nM in αCD3-stimulated Jurkat T-cells) as well as downstream signaling events, including Ca²⁺ mobilization (IC₅₀ = 52 nM in αCD3-stimulated Jurkat T-cells), IL-2 secretion (IC₅₀ = 72, 250, 380, and 390 nM, respectively, in αCD3-stimulated EL4, Jurkat, murine splenocytes, and human PBMCs), and proliferation (IC₅₀ = 430 nM against APC-induced primary human T-cell expansion). BMS-509744 is also efficacious in alleviating OVA (Cat. No. 32467) challenge-induced airway leukocytes infiltration (50% and 75% reduction, respectively, of total and eosinophil cell count; 25 mg/kg s.c.) in OVA- sensitized mice in vivo.

Cell permeable: yes

Primary Target
ITK

Target IC₅₀: 19 nM for ITK

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Kutach, A.K., et al. 2010. Chem. Biol. Drug Des.76, 154.
Das, J., et al. 2006. Bioorg. Med. Chem. Lett.16, 3706.
Lin, T.A., et al. 2004. Biochemistry43, 11056.

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