Biochem/physiol Actions

Primary TargetITK

Target IC₅₀: 19 nM for ITK

Cell permeable: yes

General description

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.

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 M) and exhibiting little or no activity against 14 other kinases (IC₅₀ ≥11 M). Inhibits ITK-dependent cellular signaling (IC₅₀﹤300 nM against αCD3-stimulated PLCγ1 Tyr phosphorylation and Ca²⁺ mobilization in Jurkat cells) in vitro and alleviate OVA (Cat. No. 32467) challenge-induced airway leukocytes infiltration (ED₅₀ = 25 mg/kg s.c.) in OVA-sensitized mice in vivo.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

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.

Packaging

5 mg in Glass bottle

Reconstitution

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

Warning

Toxicity: Standard Handling (A)