Pictilisib (GDC-0941)

製品コードS1065 バッチS106514

印刷

化学情報

Chemical Structure Synonyms RG7321 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H27N7O3S2
分子量 513.64 CAS No. 957054-30-7
Solubility (25°C)* 体外 DMSO 100 mg/mL (194.68 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Pictilisib (GDC-0941, RG7321) は、PI3Kα/δ の強力な阻害剤で、無細胞アッセイでは IC50 が 3 nM であり、p110β (11 倍) および p110γ (25 倍) に対しては控えめな選択性を示します。Pictilisib (GDC-0941) は autophagy および apoptosis を誘導します。フェーズ 2。
in vitro

Pictilisib (GDC-0941) is equipotent against PI3Kα and PI3Kδ as well as PI3Kα mutants E545-K and H1047-R, displaying modest levels of selectivity against PI3Kβ (10-fold) and PI3Kγ (25-fold), and greater levels of selectivity against members of PI3K class II, III, and IV, including C2β, Vps34, DNA-PK, and mTOR. 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. This compound 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.  It inhibits proliferation of HER2-amplified cells that harbor PIK3CA mutations with IC50 of <500 nM, and effectively inhibits both proliferation and viability of HER2-amplified breast cancer cells. It significantly inhibits the growth of HCT116, DLD1 and HT29 cells with GI50 of 1081 nM, 1070 nM and 157 nM, respectively. It also inhibits tumor cell proliferation, induces apoptosis and suppresses centroblast population.

in vivo

Pictilisib (GDC-0941) shows limited microsomal metabolism, resulting in 78% oral bioavailability . Administration of this compound at 75 mg/kg/day displays significant inhibitory effect against established human U87MG glioblastoma xenografts in female NCr athymic mice, with tumor growth inhibition of 83%. Oral administration of it at 150 mg/kg/day inhibits the growth of HER2-amplified, MDA-MB-361.1 xenografts in mice, and significantly delays the tumor progression, in association with potent induced apoptosis in tumors. Treatment with it (75 mg/kg/day) for 2 weeks induces ~40% reduction in tumor volume of spontaneous B-cell follicular lymphomas developed in PTEN+/-LKB1+/hypo mice, accompanied by ablation of phosphorylation of Akt, S6K and SGK (serum and glucocorticoid protein kinase) protein kinases.

プロトコル(参考用のみ)

キナーゼアッセイ Scintillation proximity assay
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. Recombinant human PI3Kγ is expressed as monomeric GST-fusions and purified similarly. Pictilisib (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.
細胞アッセイ 細胞株 SKBR-3, BT474-M1, AU-565, HCC-1419, ZR75-30, KPL-4, JIMT-1, BT474-EEI, HCC-1954, MCF-7, CALU-3, SKOV-3, and MKN-7 cells
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 48 and 72 hours
実験の流れ

Cells are exposed to various concentrations of Pictilisib (GDC-0941) for 48 and 72 hours. Proliferation/viability of cells is detected by using the CellTiter-Glo Luminescent Cell Viability Assay. The pAkt (Ser473), cleaved caspase-3, and cleaved PARP are analyzed by western blot. The Caspase-Glo 3/7 assay and the Cell Death Detection ELISAplus assay are used to detect caspase 3/7 activity, and apoptosis, respectively.
動物実験 動物モデル NCR nude mice implanted with MDA-MB-361.1 cells, and SCID, C.B-17/IcrHsd-Prkdcscid mice implanted subcutaneously with BT474-M1 cells
投薬量 ~150 mg/kg/day
投与方法 Oral gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/18754654/
  • https://pubmed.ncbi.nlm.nih.gov/19411071/
  • https://pubmed.ncbi.nlm.nih.gov/22415236/
  • https://pubmed.ncbi.nlm.nih.gov/21407213/
  • https://pubmed.ncbi.nlm.nih.gov/19584227/

カスタマーフィードバック

Data from [J Cell Sci, 2012, 125(Pt 5), 1259-73]

Data from [Biochim Biophys Acta, 2012, 1823, 2210-6]

Data from [Cancer Res, 2011, 71, 2750-2760]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs [ Signal Transduct Target Ther, 2025, 10(1):92] PubMed: 40113784
Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells [ Nat Commun, 2025, 16(1):4884] PubMed: 40419504
Axial nephron fate switching demonstrates a plastic system tunable on demand [ Nat Commun, 2025, 16(1):7912] PubMed: 40855070
EGFR TKIs suppress MUC1 glycosylation through the PI3K/AKT/SP1/C1GALT1 pathway to enhance TnMUC1 CAR-T efficacy in EGFR-mutant NSCLC [ Cell Rep Med, 2025, S2666-3791(25)00272-1] PubMed: 40562040
Heterogeneous Activation of Signaling Pathways and Therapeutic Vulnerabilities in KSHV-Associated Primary Effusion Lymphoma Cell Lines [ J Med Virol, 2025, 97(8):e70534] PubMed: 40751690
Separase Inhibition Enhances Gefitinib Sensitivity of Lung Cancer via PTBP1/TAK1/RIPK1-Mediated PANoptosis [ MedComm (2020), 2025, 6(11):e70432] PubMed: 41122447
Lactate shuttle between cytotrophoblast and syncytiotrophoblast in the placenta enhances ferroptosis resistance and maintains placental homeostasis: implications for early pregnancy loss [ Cell Commun Signal, 2025, 23(1):438] PubMed: 41088442
Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability [ iScience, 2025, 28(11):113682] PubMed: 41158867
Anti-Influenza Activity of 6BIGOE: Improved Pharmacological Profile After Encapsulation in PLGA Nanoparticles [ Int J Mol Sci, 2025, 26(9)4235] PubMed: 40362470
Cartilage Oligomeric Matrix Protein Promotes Radiation Resistance in Non-Small Cell Lung Cancer In Vitro [ Int J Mol Sci, 2025, 26(6)2465] PubMed: 40141111

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人間や獣医の診断であるか治療的な使用のためにでない。

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