419820

BMS-509744

≥97% (HPLC), powder, ITK inhibitor, Calbiochem^®

• Synonym(s): ITK Inhibitor, BMS-509744
• Empirical Formula (Hill Notation): C₃₂H₄₁N₅O₄S₂
• CAS Number: 439575-02-7
• Molecular Weight: 623.83
• MDL number: MFCD18782598
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Product Name: ITK Inhibitor, BMS-509744,
• assay: ≥97% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: pale yellow
• solubility: DMSO: 100 mg/mL
• shipped in: ambient
• storage temp.: −20°C
• SMILES string: [s]1c(ncc1Sc3c(cc(c(c3)C(=O)N4CCN(CC4)C(=O)C)OC)C)NC(=O)c2ccc(cc2)CNC(C(C)(C)C)C
• InChI: 1S/C32H41N5O4S2/c1-20-16-26(41-7)25(30(40)37-14-12-36(13-15-37)22(3)38)17-27(20)42-28-19-34-31(43-28)35-29(39)24-10-8-23(9-11-24)18-33-21(2)32(4,5)6/h8-11,16-17,19,21,33H,12-15,18H2,1-7H3,(H,34,35,39)
• InChI key: ZHXNIYGJAOPMSO-UHFFFAOYSA-N

Description

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.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
ITK

Target IC₅₀: 19 nM for ITK

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

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.

Legal Information

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

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable