5.09226

PI 3-K Inhibitor XXI, GDC-0941

• Synonyme(s) : PI 3-K Inhibitor XXI, GDC-0941, GDC0941, 2-(1H-Indazol-4-yl)-6-(4-methylsulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2- d]pyrimidine, 4-(2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine
• Formule empirique (notation de Hill): C₂₃H₂₇N₇O₃S₂
• Numéro CAS: 957054-30-7
• Poids moléculaire : 513.64
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• Pureté: ≥99% (HPLC)
• Niveau de qualité: 100
• Forme: solid
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: white
• Solubilité: DMSO: 50 mg/mL
• Température de stockage: 2-8°C
• InChI: 1S/C23H27N7O3S2/c1-35(31,32)30-7-5-28(6-8-30)15-16-13-20-21(34-16)23(29-9-11-33-12-10-29)26-22(25-20)17-3-2-4-19-18(17)14-24-27-19/h2-4,13-14H,5-12,15H2,1H3,(H,24,27)
• Clé InChI: LHNIIDJUOCFXAP-UHFFFAOYSA-N

Description

Description générale

A cell-permeable thienopyrimidine compound that acts as a potent, ATP-competitive inhibitor against class IA (IC₅₀ = 3 nM/p110α, 33 nM/p110β, 3 nM/p110δ) & IB (IC₅₀ = 75 nM/p110γ) PI 3-K kinases, including the two known p110α hot spot mutants E454K & H1047R (IC₅₀ = 3 nM), while exhibiting much reduced or little potency against more than 200 other kinases, including TrkA, class II C2β, class IV mTOR & DNA-PK (IC₅₀ = 2.85, 0.67, 0.58, and 1.23 µM, respectively) and class III Vps34 (IC₅₀ >10 µM). Effectively inhibits cellular Akt S473 phosphorylation (IC₅₀ = 28 to 46 nM) as well as proliferation in cancer cultures in vitro (GI₅₀ = 280 to 950 nM) and completely prevents the expansion of U87MG glioblastoma xenograft in mice in vivo (by 83%; 75 mg/kg/d p.o. for 21 days). Oral bioavailability is reported in human, dog, mouse, and rat.

A cell-permeable thienopyrimidine compound that acts as a potent, ATP-competitive inhibitor against class IA (IC₅₀ = 3 nM/p110α, 33 nM/p110β, 3 nM/p110δ) & IB (IC₅₀ = 75 nM/p110γ) PI 3-K kinases, including the two known p110α hot spot mutants E454K & H1047R (IC₅₀ = 3 nM), while exhibiting much reduced or little potency against more than 200 other kinases, including TrkA, class II C2β, class IV mTOR & DNA-PK (IC₅₀ = 2.85, 0.67, 0.58, and 1.23 µM, respectively) and class III Vps34 (IC₅₀ >10 µM). Effectively inhibits cellular Akt S473 phosphorylation (IC₅₀ = 46 nM/U87MG, 37 nM/PC3, and 28 nM/MDA-MB-361) as well as proliferation in cancer cultures in vitro (GI₅₀ = 950/U87MG, 280/PC3, and 720 nM/MDA-MB-361) and greatly prevents the expansion of U87MG glioblastoma xenograft in mice in vivo (by 83%; 75 mg/kg/d p.o. for 21 days). Oral bioavailability is reported in human, dog, mouse, and rat.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
PI 3-K

Reversible: yes

Conditionnement

Packaged under inert gas

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.

Use only fresh DMSO for reconstitution.

Autres remarques

Tabe, Y., et al. 2014. Acta Haematol.131, 59.
Ware, J.A., et al. 2013. Mol. Pharm.10, 4047.
Junttila,.T., et al. 2009. Cancer Cell15, 429.
Raynaud, F.I., et al. 2009. Mol Cancer Ther.8, 1725.
Folkes, A. J., et al. 2008. J. Med. Chem.51, 5522.

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