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Pictilisib

Pictilisib

产品编号 T1994   CAS 957054-30-7
别名: RG7321, GDC-0941

Pictilisib (GDC-0941) 是一种PI3Kα/δ抑制剂,IC50为 3 nM。它对110β和 p110γ 具有适度的选择性,分别为11倍和25倍。

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Pictilisib Chemical Structure
Pictilisib, CAS 957054-30-7
规格 价格/CNY 货期 数量
5 mg ¥ 531 现货
10 mg ¥ 697 现货
50 mg ¥ 1,698 现货
100 mg ¥ 2,683 现货
200 mg ¥ 3,775 现货
1 mL * 10 mM (in DMSO) ¥ 598 现货
其他形式的 Pictilisib:
千万补贴 助力科研
BCA蛋白浓度测定试剂盒限时半价
Venetoclax限时半价
产品目录号及名称: Pictilisib (T1994)
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选择批次  
纯度: 99.97%
纯度: 99.69%
纯度: 99.22%
纯度: 99%
更多批次查询请联系客服
生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 Pictilisib (GDC-0941) (GDC-0941) is a potent pan inhibitor of class I catalytic subunits of PI3K (IC50s: 3/33/3/75 nM for p110α/β/δ/γ).
靶点活性 p110α:3 nM (cell free), p110δ:3 nM (cell free), p110β:33 nM (cell free)
体外活性 GDC-0941 is a potent inhibitor of cell proliferation in these cell lines with submicromolar IC50s. Potent inhibition of Akt (Ser473) phosphorylation was observed in U87MG, PC3, and MDA-MB-361 cells with IC50s of 46, 37, and 28 nM, respectively [1]. In comparison to single-agent treatments, the combination of GDC-0941 and docetaxel reduced tumor cell viability by 80% or greater in the breast cancer cell lines tested in vitro. A Bliss sum of 0 was determined in the MDA-MB-453 cell line indicating an additive combination effect whereas Bliss sums > 0 were calculated in the other tumor cell lines indicating a synergistic effect [2]. Treatment with 250 nM GDC-0941 for 2 hr resulted in 40%–85% inhibition of pAKT in all cell lines tested. Inhibition of the PI3K/AKT pathway by GDC-0941 was reflected as a dose-dependent reduction in cell proliferation/viability. GDC-0941 inhibited the growth of both trastuzumab-sensitive and -insensitive cells. The IC50 values for GDC-0941 ranged between 150 and 950 nM and did not correlate with trastuzumab sensitivity [3].
体内活性 Treatment of animals bearing MCF7-neo/HER2 breast cancer xenografts with 7.5 mg/kg docetaxel or 150 mg/kg GDC-0941 led to tumor growth delay and tumor stasis, respectively. The combination of 100 mg/kg GDC-0941 and docetaxel resulted in tumor stasis during the treatment period that was sustained after dosing ended [2]. AZD8055 (20?mg/kg) or GDC-0941 (75?mg/kg) administration induced a transient increase in blood glucose levels. Treatment with either AZD8055 or GDC-0941 led to a marked inhibition of Akt activity as well as phosphorylation of Thr308 and Ser473. Phosphorylation of the Akt substrates PRAS40 and Foxo-1/3a were also inhibited by AZD8055 or GDC-941 [4].
激酶实验 Recombinant human PI3Kα, PI3Kβ, and PI3Kδ are coexpressed in a Sf9 baculovirus system with the p85α regulatory subunit and purified as GST-fusion proteins using affinity chromatography on glutathione-sepharose. Recombinant human PI3Kγ is expressed as monomeric GST-fusions and purified similarly. GDC-0941 is dissolved in DMSO and added to 20 mM Tris-HCl (pH 7.5) containing 200 μg yttrium silicate (Ysi) polylysine SPA beads, 4 mM MgCl2, 1 mM dithiothreitol (DTT), 1 μM ATP, 0.125 μCi [γ-33P]-ATP, and 4% (v/v) DMSO in a total volume of 50 μL. The recombinant GST-fusion of PI3Kα (5 ng), PI3Kβ (5 ng), PI3Kδ (5 ng), or PI3Kγ (5 ng) is added to the assay mixture to initiate the kinase reaction. After incubation for 1 hour at room temperature, the kinase reaction is terminated with 150 μL PBS. The mixture is then centrifuged for 2 minutes at 2000 rpm and read using a Wallac Microbeta counter. The reported IC50 values are calculated using a sigmoidal, dose-response curve fit in MDL Assay Explorer [1].
细胞实验 All drug treatments were tested in quadruplicate during a 4-day incubation period, and the relative number of viable cells was estimated using CellTiter-Glo. Total luminescence was measured on a Wallac Multilabel Reader. Cells were treated simultaneously with docetaxel (dose range = 0.0003–0.020 μmol/L) or GDC-0941 (dose range = 0.083–5 μmol/L) in an 8 × 10 matrix of concentrations chosen to encompass clinically relevant doses (24). The concentration of drug resulting in EC50 was determined using Prism software. Combination synergy of GDC-0941 and docetaxel was determined by Bliss independence analyses. A Bliss expectation for a combined response (C) was calculated by the equation: C = (A + B) ? (A × B) where A and B are the fractional growth inhibitions of drug A and B at a given dose. The difference between the Bliss expectation and the observed growth inhibition of the combination of drugs A and B at the same dose is the 'Delta.Bliss.' Delta.Bliss scores were summed across the dose matrix to generate a Bliss sum. Bliss sum = 0 indicates that the combination treatment is additive (as expected for independent pathway effects); Bliss sum > 0 indicates activity greater than additive (synergy); and Bliss sum < 0 indicates the combination is less than additive (antagonism). Statistical analysis comparing the Bliss sums for each cell line was conducted by the Student t-test [2].
动物实验 Female nu/nu mice were inoculated subcutaneously with MCF7-neo/HER2 or MX-1 breast cancer cells. When tumors reached a mean volume of 200 to 250 mm3, animals were size-matched and distributed into groups consisting of 10 animals per group. Docetaxel formulated in 3% EtOH, 97% saline was administered intravenously once weekly. GDC-0941, formulated in MCT (0.5% methylcellulose, 0.2% Tween-80) was dosed orally and daily. MAXF1162 is a HER2+/ER+/PR+ patient-derived breast cancer tumor xenograft model established by directly implanting tumors subcutaneously from patient to NMRI nu/nu mice. Tumor volume was calculated as follows: tumor size (mm3) = (longer measurement × shorter measurement2) × 0.5. Tumor sizes were recorded twice weekly over the course of a study. Following data analysis, P values were determined using the Dunnett t test. For pharmacodynamic studies, tumor samples (n = 4) were immediately frozen or fixed in 10% neutral-buffered formalin. Tumors were dissociated in cell extraction buffer, and lysates were analyzed by Western blotting as described above. Immunohistochemistry was conducted using 5-μm paraffin sections of formalin-fixed tissue on a Ventana Benchmark XT instrument by deparaffinization, treatment with antigen retrieval buffer, and incubation with anti-cleaved caspase-3 primary antibody at 37°C. Bound antibody was detected using DABMap technology, and sections were counterstained with hematoxylin [2].
别名 RG7321, GDC-0941
分子量 513.64
分子式 C23H27N7O3S2
CAS No. 957054-30-7

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

DMSO: 41 mg/mL (79.8 mM)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

H2O: < 1 mg/mL (insoluble or slightly soluble)

溶液配制表

可选溶剂 浓度 体积 质量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.9469 mL 9.7344 mL 19.4689 mL 48.6722 mL
5 mM 0.3894 mL 1.9469 mL 3.8938 mL 9.7344 mL
10 mM 0.1947 mL 0.9734 mL 1.9469 mL 4.8672 mL
20 mM 0.0973 mL 0.4867 mL 0.9734 mL 2.4336 mL
50 mM 0.0389 mL 0.1947 mL 0.3894 mL 0.9734 mL

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TargetMol Library Books参考文献

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. J Med Chem. 2008 Sep 25;51(18):5522-32. 2. Wallin JJ, 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 Jul 15;18(14):3901-11. 3. Junttila TT, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009 May 5;15(5):429-40. 4. García-Martínez JM, et al. Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice. Br J Cancer. 2011 Mar 29;104(7):1116-25. 5. Quan C, Chen Y, Wang X, et al. Loss of histone lysine methyltransferase EZH2 confers resistance to tyrosine kinase inhibitors in non-small cell lung cancer. cancer letters. 2020

TargetMol Library Books文献引用

1. Liang C, Yu X, Xiong N, et al. Pictilisib Enhances the Antitumor Effect of Doxorubicin and Prevents Tumor-Mediated Bone Destruction by Blockade of PI3K/AKT Pathway. Frontiers in oncology. 2020, 10. 2. Zhao Deng,Chenbin Cui,Yanan Wang,Jiangjin Ni, et al. FSGHF3 and peptides, prepared from fish skin gelatin, exert a protective effect on DSS-induced colitis via the Nrf2 pathway. Food & Function. 2020 3. Zhao Deng,Chenbin Cui,Yanan Wang,Jiangjin Ni, et al. FSGHF3 and peptides, prepared from fish skin gelatin, exert a protective effect on DSS-induced colitis via the Nrf2 pathway. Food & Function. 2020
Supinoxin Cedrelone Genistein Sunitinib Malate YK-4-279 LQZ-7F BI 2536 CPI-203

相关化合物库

该产品包含在如下化合物库中:
抑制剂库 药物功能重定位化合物库 抗癌临床化合物库 激酶抑制剂库 抗癌活性化合物库 抗癌药物库 抗癌细胞代谢库 癌细胞分化化合物库 神经再生化合物库 血液病分子库

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Keywords

Pictilisib 957054-30-7 Apoptosis Autophagy PI3K/Akt/mTOR signaling PI3K Inhibitor inhibit Phosphoinositide 3-kinase RG7321 RG 7321 GDC 0941 GDC-0941 GDC0941 RG-7321 inhibitor

 

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