5.09226

PI 3-K Inhibitor XXI, GDC-0941

• 동의어(들): 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
• 실험식(Hill 표기법): C₂₃H₂₇N₇O₃S₂
• CAS Number: 957054-30-7
• Molecular Weight: 513.64
• UNSPSC 코드: 12352200
• NACRES: NA.77

속성

• 분석: ≥99% (HPLC)
• Quality Level: 100
• 형태: solid
• 제조업체/상표: Calbiochem^®
• 저장 조건: OK to freeze; protect from light
• 색상: white
• solubility: DMSO: 50 mg/mL
• 저장 온도: 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)
• InChI key: LHNIIDJUOCFXAP-UHFFFAOYSA-N

설명

일반 설명

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.

생화학적/생리학적 작용

Cell permeable: yes

Primary Target
PI 3-K

Reversible: yes

포장

Packaged under inert gas

경고

Toxicity: Standard Handling (A)

재구성

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.

기타 정보

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.

법적 정보

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

안전성 정보

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable