| GDC-0941 is a potent inhibitor of p110a and p110d (IC50 = 3nM). It selectively binds to PI3K isoforms in an ATP-competitive manner, inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway. GDC-0941 is a phosphatidylinositol 3-kinase (PI3K) inhibitor. Folkes, A.J., 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. J. Med. Chem. 51: 5522-5532 (2008). GDC-0941 inhibited the growth of >70% of breast cancer cell lines tested, with EC50s <1 µM. GDC-0941 also demonstrated antitumor activity in preclinical models of breast cancer. Yao, E., et al. Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab. Clin. Cancer Res. 15: 4147-4156 (2009). The combination of GDC-0941 with trastuzumab is highly efficacious in the treatment of cancer cells in vitro and tumors in vivo. GDC-0941 also has antitumor activity in the treatment of trastuzumab-resistant cells and tumors. Junttila, T.T., et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 15: 429-440 (2009). GDC-0941 inhibits the activity of recombinant PI3K in vitro with IC50s of 0.003 µM (P110alpha), 0.033 µM (P110beta), 0.003 µM (P110delta), 0.075 µM (P110gamma), 0.58 µM (mTOR) and 1.23 µM (DNA-PK). GDC-0941 inhibited the growth of tumor cells in vitro with IC50s of 0.95 µM (U87MG), 0.07 µM (IGROV-1), 0.15 µM (DETROIT 562), 0.28 µM (PC3) and 0.54 µM (SKOV-3). GDC-0941 also inhibited the growth of U87 MG glioblastoma xenografts and IGROV-1 ovarian cancer xenografts in mice. Raynaud, F.I., 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. Mol. Cancer Ther. 8: 1725-1738 (2009). Synonyms: 2-(1H-indazol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[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, GDC 0941, GDC 941, GNE 0941, Pictilisib, Pictrelisib CAS No: 957054-30-7 Molecular Formula: C23H27N7O3S2 Molecular Weight: 513.64 Appearance: Supplied as an off-white solid. Purity: 99% (HPLC, TLC) Solubility: Soluble in DMSO at 66mg/ml, very poorly soluble in ethanol, very poorly soluble in water, maximum solubility in plain water is estimated to be about 10-50uM buffers, serum, or other additives may increase or decrease the aqueous solubility. Elemental Analysis: Calculated: %C: 53.78, %H: 5.30, %N: 19.09, %S: 12.49 Storage and Stability: Lyophilized and reconstituted products are stable for 6 months after receipt at -20C. Reconstitute with DMSO. Aliquot to avoid repeated freezing and thawing. Store at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer. Important Note: This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications without the expressed written authorization of United States Biological. Toxicity and Hazards: All products should be handled by qualified personnel only, trained in laboratory procedures. |
