5.09226

PI 3-K Inhibitor XXI, GDC-0941

• Synonym(e): 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
• Empirische Formel (Hill-System): C₂₃H₂₇N₇O₃S₂
• CAS-Nummer: 957054-30-7
• Molekulargewicht: 513.64
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥99% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: white
• Löslichkeit: DMSO: 50 mg/mL
• Lagertemp.: 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)
• InChIKey: LHNIIDJUOCFXAP-UHFFFAOYSA-N

Beschreibung

Allgemeine Beschreibung

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.

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
PI 3-K

Reversible: yes

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

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.

Sonstige Hinweise

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.

Rechtliche Hinweise

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

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable