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Pictilisib

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Chemical Structure| 957054-30-7 同义名 : GDC-0941;GNE-0941;Pictrelisib;RG7321
CAS号 : 957054-30-7
货号 : A198456
分子式 : C23H27N7O3S2
纯度 : 99%+
分子量 : 513.636
MDL号 : MFCD11616196
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(204.43 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+30% PEG 300+5% Tween 80+water 5 mg/mL

生物活性
靶点

  • p110γ

    p110γ, IC50:75 nM

  • p110β

    p110β, IC50:33 nM

  • p110α

    p110α, IC50:3 nM

  • p110δ

    p110δ, IC50:3 nM
描述 Phosphatidylinositol-3-kinases (PI3Ks) are lipid kinases that catalyze the phosphorylation of the 3-hydroxyl position of phosphatidylinositides and participate in several cellular process. Up to now, there are eight PI3 kinases have been identified, which are divided into classes IA, 1B, II, and III based on the sequence homology and substrate preference. GDC-0941 is a potent, selective and orally bioavailable inhibitor of class I PI3Ks (p110α IC50=3nM, p110δ IC50=3nM, p110β IC50=33nM, p110γ IC50=75nM, measured by scintillation proximity assay), with less potency to mTOR (IC50=0.58μM, measured by HTRF assay)[1]. GDC-0941 is a derivative of PI-103, a dual PI3K/mTOR inhibitor, and has good pharmacokinetic properties. Its oral bioavailability is up to 78% in subcutaneous U-87 MG xenograft mice and shows sustained and remarkable inhibition of Akt phosphorylation and tumor growth, up to 98%[2]. GDC-0941 barely penetrated through the intact BBB[3].
作用机制 GDC-0941 is a potent, ATP competitive inhibitor of p110α with Ki value of 10.2±4.4 nM.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
22RV1 Growth Inhibition Assay IC50=2.45617 μM SANGER
5637 Growth Inhibition Assay IC50=2.71035 μM SANGER
639-V Growth Inhibition Assay IC50=1.50245 μM SANGER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02430363 Glioblastoma Phase 1 Phase 2 Unknown June 2018 United States, Massachusetts ... 展开 >> Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, Texas M D Anderson Cancer Center Houston, Texas, United States, 77030 Belgium UCL- Cliniques Universitaires Saint Luc Brussels, Belgium Germany St Johannes Hospital Duisburg, Germany, 47166 Italy Spedali Civili di Brescia Brescia, Italy IRCCS San Raffaele Milan, Italy Poland Lower-Silesian Oncology Centre Wroclaw, Lower-Silesian, Poland, 53413 Russian Federation Pavlov State Medical University St. Petersburg, Russian Federation, 197089 Spain Hospital Universitario Germans Trias I Pujol Barcelona,, Spain Switzerland Universitätsklinik für Frauenheilkunde Bern, Switzerland Ukraine Regional Cancer Center Dnepropetrovsk, Ukraine, 49000 National Institute of Cancer Kiev, Ukraine, 03035 United Kingdom Royal Victoria Hospital Belfast, Ulster, United Kingdom, BT12 6BA 收起 <<
NCT02389842 Advanced Solid Tumours ... 展开 >> Breast Cancer 收起 << Phase 1 Unknown August 2017 United Kingdom ... 展开 >> The Royal Marsden NHS Foundation Trust Recruiting London, United Kingdom, SM2 5PT Contact: Timothy Yap, PhD    02086613539    timothy.yap@icr.ac.uk    Principal Investigator: Timothy Yap, PhD          The Christie NHS Foundation Trust Not yet recruiting Manchester, United Kingdom, M20 4BX Contact: Anne Amstrong, MBBS    0161 446 3746    elaine.mercer@christie.nhs.uk    Principal Investigator: Anne Armstrong, MBBS 收起 <<
NCT02092831 Healthy Volunteer Phase 1 Completed - United States, Wisconsin ... 展开 >> Madison, Wisconsin, United States, 53704 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.95mL

0.39mL

0.19mL

9.73mL

1.95mL

0.97mL

19.47mL

3.89mL

1.95mL
参考文献

[1]Folkes AJ, Ahmadi K, 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. 2008 Sep 25;51(18):5522-32.

[2]Raynaud FI, Eccles SA, 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. 2009 Jul;8(7):1725-38.

[3]Salphati L, Shahidi-Latham S, et al. Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. Drug Metab Dispos. 2014 Jul;42(7):1110-6.

[4]Garcia-Martínez JM, Wullschleger S, et al. Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice. Br J Cancer. 2011;104(7):1116-25.

[5]Wallin JJ, Guan J, et al. GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of docetaxel in human breast cancer models by increasing cell death in vitro and in vivo. Clin Cancer Res. 2012;18(14):3901-11.

[6]Burrows N, Babur M, et al. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways. J Clin Endocrinol Metab. 2011;96(12):E1934-43.