GDC-0941 --- PI3K Inhibitor

GDC-0941 is a highly potent, selective and orally bioavailable class-I PI3K kinase inhibitor. Its IC50 for PI3K p110 α, β, δ and γ isoforms are 3 nM, 33 nM, 3 nM, and 75 nM, respectively; and its IC50 for DNA-PK and mTOR are 1230 nM and 580 nM. It potently inhibits the phosphorylation of Akt in U87MG, PC3, and MDA-MB-361 cells with IC50 of 46 nM, 37 nM, and 28 nM, respectively. It also inhibits the proliferation of U87MG, A2780, PC3, and MDA-MB-361 cells with IC50 of 0.95 μM, 0.14 μM, 0.28 μM, and 0.72 μM, respectively. GDC-0941 inhibits tumor cell proliferation, induces apoptosis and suppresses centroblast population. It is now in Phase I clinical trials targeting several advanced or metastatic solid tumors.

Product information

CAS Number: 957054-30-7

Molecular Weight: 513.64

Formula: C23H27N7O3S2

Related CAS Number:

957054-33-0 (mesylate)

Chemical Name: 4-(2-(1H-indazol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine

Smiles: CS(=O)(=O)N1CCN(CC2=CC3=NC(=NC(=C3S2)N2CCOCC2)C2C=CC=C3NN=CC=23)CC1

InChiKey: LHNIIDJUOCFXAP-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

GDC-0941 was used at 1-10 µM in vitro and in cellular assays.

In Vivo:

GDC-0941 was orally dosed to mice at 75-150 mg/kg once per day for two weeks.

References:

1. Folkes AJ, et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer.(2008) J. Med. Chem. 51(18), 5522-32.
2. Raynaud FI, et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. (2009) Mol. Cancer Ther. 8(7), 1725-38.
3. Zheng L, et al. GDC-0941 sensitizes breast cancer to ABT-737 in vitro and in vivo through promoting the degradation of Mcl-1.(2011) Cancer Lett. 309(1):27-36.
4. Haagensen EJ, et al. The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition. (2012) Br J Cancer. 106(8):1386-94.

Products are for research use only. Not for human use.

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