419820

BMS-509744

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

• Synonyme(s) : ITK Inhibitor, BMS-509744
• Formule empirique (notation de Hill) : C₃₂H₄₁N₅O₄S₂
• Numéro CAS: 439575-02-7
• Poids moléculaire : 623.83
• Numéro MDL: MFCD18782598
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• Nom du produit: ITK Inhibitor, BMS-509744,
• Essai: ≥97% (HPLC)
• Niveau de qualité: 100
• Forme: powder
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: pale yellow
• Solubilité: DMSO: 100 mg/mL
• Conditions d'expédition: ambient
• Température de stockage: −20°C
• Chaîne SMILES: [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)
• Clé InChI: ZHXNIYGJAOPMSO-UHFFFAOYSA-N

Description

Description générale

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.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
ITK

Target IC₅₀: 19 nM for ITK

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

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

Autres remarques

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.

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable