Name | 4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine |
Synonyms | GDC0941 GDC-0941 Pictilisib GDC-0941 free base GDC-0941 bismesylate 4-(2-(1H-Indazol-4-yl)-6-((4-(Methylsulfonyl)piperazin-1-yl)Methyl)thieno[3,2-d] 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine 4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine 2-(1H-Indazol-4-yl)-6-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-4-(4-morpholinyl)thieno[3,2-d]pyrimidine Thieno[3,2-d]pyrimidine, 2-(1H-indazol-4-yl)-6-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-4-(4-morpholinyl)- |
CAS | 957054-30-7 |
EINECS | 1312995-182-4 |
InChI | InChI=1/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) |
Molecular Formula | C23H27N7O3S2 |
Molar Mass | 513.64 |
Density | 1.53±0.1 g/cm3(Predicted) |
Melting Point | >200oC (dec.) |
Solubility | Soluble in DMSO, not in water |
Appearance | White powder solid. |
Color | White/off-white |
pKa | 12.22±0.40(Predicted) |
Storage Condition | -20°C |
Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
Refractive Index | 1.753 |
Use | Pictilisib (GDC-0941) is a potent inhibitor of PI3Kα/δ with an IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold). |
In vitro study | GDC-0941 also acts equivalently on PI3Kα and PI3Kδ and PI3Kα mutant E545-K and H1047-R, selectively on PI3Kβ(10 times) and PI3Kγ(25 times), and selectively on PI3K II, III, and Class IV members, including, C2β, Vps34, DNA-PK, and mTOR. GDC-0941 effectively inhibited Akt phosphorylation in U87MG, PC3, and MDA-MB-361 cells with IC50 values of 46 nM, 37 nM, and 28 nM, respectively. GDC-0941 inhibition U87MG, A2780, PC3, and MDA-MB-361 cell proliferation, IC50 were 0.95 μm, 0.14 μm, 0.28 μm, and 0.72 μm, respectively. GDC-0941 treatment effectively inhibited proliferation of Trastuzumab-sensitive and insensitive HER2 amplified cells with an IC50 of 149-944 nM, independent of Trastuzumab sensitivity. GDC-0941 inhibit the proliferation of HER2 amplified cells containing the PIK3CA mutation, IC50<500 nM, and effectively inhibit the proliferation and viability of anti-trastuzumab HER2 amplified breast cancer cells. GDC-0941 significantly inhibited the growth of HCT116, DLD1 and HT29 cells with GI50 of 1081 nM, 1070 nM and 157 nM, respectively. |
In vivo study | In microsomes, GDC-0941 has only limited metabolism with an oral bioavailability of 78%. GDC-0941 Female NCr athymic mice bearing human U87MG malignant glial xenografts were treated at a dose of 75 mg/kg per day, and the growth of the tumors was significantly inhibited, with a tumor growth inhibition rate of 83%. GDC-0941 daily oral treatment of mice bearing her2-amplified anti-Trastuzumab MDA-MB-361.1 xenografts at a dose of 150 mg/kg inhibited tumor growth and significantly delayed tumor regression, associated with strong induced apoptosis in the tumors. GDC-0941 treatment of PTEN bearing spontaneous B- cell follicular lymphoma at a dose of 75 mg/kg per day |
HS Code | 29350090 |
Reference Show more | 1: De Wolf E, De Wolf C, Richardson A. ABT-737 and pictilisib synergistically enhance pitavastatin-induced apoptosis in ovarian cancer cells. Oncol Lett. 2018 Feb;15(2):1979-1984. doi: 10.3892/ol.2017.7516. Epub 2017 Dec 5. PubMed PMID: 29434898; PubMed Central PMCID: PMC5778268. 2: Keegan NM, Gleeson JP, Hennessy BT, Morris PG. PI3K inhibition to overcome endocrine resistance in breast cancer. Expert Opin Investig Drugs. 2018 Jan;27(1):1-15. doi: 10.1080/13543784.2018.1417384. Epub 2018 Jan 6. Review. PubMed PMID: 29252036. 3: Langhans J, Schneele L, Trenkler N, von Bandemer H, Nonnenmacher L, Karpel-Massler G, Siegelin MD, Zhou S, Halatsch ME, Debatin KM, Westhoff MA. The effects of PI3K-mediated signalling on glioblastoma cell behaviour. Oncogenesis. 2017 Nov 29;6(11):398. doi: 10.1038/s41389-017-0004-8. PubMed PMID: 29184057. 4: Yang W, Hosford SR, Traphagen NA, Shee K, Demidenko E, Liu S, Miller TW. Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer. FASEB J. 2018 Jan 3:fj201700477R. doi: 10.1096/fj.201700477R. [Epub ahead of print] PubMed PMID: 29127189. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 1.947 ml | 9.734 ml | 19.469 ml |
5 mM | 0.389 ml | 1.947 ml | 3.894 ml |
10 mM | 0.195 ml | 0.973 ml | 1.947 ml |
5 mM | 0.039 ml | 0.195 ml | 0.389 ml |