Apitolisib (GDC-0980)

製品コードS2696 バッチS269602

印刷

化学情報

Chemical Structure Synonyms RG7422, GNE 390 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H30N8O3S
分子量 498.6 CAS No. 1032754-93-0
Solubility (25°C)* 体外 DMSO 20 mg/mL (40.11 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 Apitolisib (GDC-0980, RG7422, GNE 390) is a potent, class I PI3K inhibitor for PI3Kα/β/δ/γ with IC50 of 5 nM/27 nM/7 nM/14 nM in cell-free assays, respectively. Also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases. Apitolisib activates autophagy and apoptosis simultaneously in pancreatic cancer cells. Phase 2.
in vitro Apitolisib (GDC-0980) shows potent and selective inhibitory activities against class I PI3K and mTOR kinase versus a large panel of kinases, with Ki of 17 nM for mTOR and IC50 of 5 nM, 27 nM, 7 nM, and 14 nM for PI3Kα, β, δ, and γ, respectively. [1] In vitro, this compound significantly inhibits cell proliferation in PC3 and MCF7 cells with IC50 of 307 nM and 255 nM, respectively. [1] A recent study shows that it reduces cancer cell viability by inhibiting cell-cycle procession and inducing apoptosis with most potency in prostate (IC50 < 200 nM 50%, <500 nM 100%), breast (IC50 <200 nM 37%, <500 nM 78%) and NSCLC lines (IC50 <200 nM 29%, <500 nM 88%) and less potency in pancreatic (IC50 <200 nM 13%, <500 nM 67%) and melanoma cell lines (IC50 <200 nM 0%, <500 nM 33%). [2]
in vivo Apitolisib (GDC-0980) exhibits significant antitumor activity at a dose of 1 mg/kg by causing tumor growth delay in both PC-3 and MCF-7 neo/HER2 xenograft models. Furthermore, this compound results in tumor stasis or regressions at the maximum tolerated dose of 7.5 mg/kg. [1] In mice, intravenous administration at 1 mg/kg leads to low clearance (Clp: 9.2 mL/min/kg, Vss: 1.7 L/kg). While, oral administration at 5 mg/kg in 80% PEG400 and at 50 mg/kg as a crystalline suspension in 0.5% methylcellulose/0.2% Tween-80 also results in favorable pharmacokinetic parameters. [1]
特徴 A potent, selective, and orally available inhibitor of PI3Kα, β, δ, γ and mTOR.

プロトコル(参考用のみ)

キナーゼアッセイ Enzymatic activity
Apitolisib (GDC-0980) is evaluated through enzymatic activity assays for Class I PI3K isoforms using a fluorescence polarization method that monitors the formation of 3,4,5-inositoltriphosphate, which competes with fluorescently labeled PIP3 for binding to the GRP-1 pleckstrin homology domain protein. An increase in phosphatidyl inositide-3-phosphate product results in a decrease in fluorescence polarization signal as the labeled fluorophore is displaced from the GRP-1 protein binding site. Class I PI3K isoforms are expressed and purified as heterodimeric recombinant proteins. PI3K isoforms are assayed under initial rate conditions in the presence of 10 mM Tris (pH 7.5), 25 μM ATP, 9.75 μM PIP2, 5% glycerol, 4 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 2% (v/v) DMSO at the following concentrations for each isoform: PI3Kα,β at 60 ng/mL; PI3Kγ at 8 ng/mL; PI3Kδ at 45 ng/mL. After assay for 30 minutes at 25°C, reactions are terminated with a final concentration of 9 mM EDTA, 4.5 nM TAMRA-PIP3, and 4.2 μg/mL GRP-1 detector protein before reading fluorescence polarization on an Envision plate reader. IC50s are calculated from the fit of the dose−response curves to a 4-parameter equation. Human recombinant mTOR(1360−2549) is expressed and purified from insect cells and assayed using a Lanthascreen fluorescence resonance energy transfer format in which phosphorylation of recombinant green fluorescent protein (GFP)-4-EBP1 is detected using a terbium-labeled antibody to phospho-threonine 37/46 of 4-EBP1. Reactions are initiated with ATP and conducted in the presence of 50 mM Hepes (pH 7.5), 0.25 nM mTOR, 400 nM GFP-4E-BP1, 8 μM ATP, 0.01% (v/v) Tween 20, 10 mM MnCl2, 1 mM EGTA, 1 mM dithiothreitol, and 1% (v/v) DMSO. Assays are conducted under initial rate conditions at room temperature for 30 minutes before terminating the reaction and detecting product in the presence of 2 nM Tb-anti-p4E-BP1 antibody and 10 mM EDTA. Dose−response curves are fit to an equation for competitive tight-binding inhibition and apparent Ki' s are calculated using the determined Km for ATP of 6.1 μM.
細胞アッセイ 細胞株 PC3 and MCF7.1
濃度 0 to 10 μM
反応時間 72 hours or 96 hours
実験の流れ Antiproliferative cellular assays are conducted using PC3 and MCF7.1 human tumor cell lines. MCF7.1 is an in vivo selected line and originally derived from the parental human MCF7 breast cancer cell line. Cell lines are cultured in RPMI supplemented with 10% fetal bovine serum, 100 units/mL penicillin, and 100 μg/mL streptomycin, 10 mM HEPES, and 2 mM glutamine at 3°C under 5% CO2. MCF7.1 cells or PC3 cells are seeded in 384-well plates in media at 1000 cells/well or 3000 cells/well, respectively, and incubated overnight prior to the addition of Apitolisib (GDC-0980) to a final DMSO concentration of 0.5% v/v. MCF7.1 cells and PC3 cells are incubated for 3 days and 4 days, respectively, prior to the addition of CellTiter-Glo reagen and reading of luminescence using an Analyst plate reader. For antiproliferative assays, a cytostatic agent such as aphidicolin and a cytotoxic agent such as staurosporine are included as controls. Dose−response curves are fit to a 4-parameter equation and relative IC50s are calculated using Assay Explorer software.
動物実験 動物モデル PC3 and MCF7.1 cells are injected s.c. into the right hind flank of athymic nu/nu (nude) mice.
投薬量 ≤7.5 mg/kg
投与方法 Administered via p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/21981714/
  • https://pubmed.ncbi.nlm.nih.gov/21998291/
  • https://pubmed.ncbi.nlm.nih.gov/22532600/

カスタマーフィードバック

Data from [Data independently produced by Breast Cancer Res, 2014, 16(4), 406]

Data from [Data independently produced by PLoS One, 2014, 9(9), e105919]

, , Dr.Wang Wei from NanFang Hospital

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：

Depleting the action of EZH2 through PI3K-mTOR inhibition to overcome metastasis and immunotherapy resistance in triple-negative breast cancer [ Mol Cancer Ther, 2025, 10.1158/1535-7163.MCT-24-0693] PubMed: 40497697
Establishment, characterization, and biobanking of 36 pancreatic cancer organoids: prediction of metastasis in resectable pancreatic cancer [ Cell Oncol (Dordr), 2024, 10.1007/s13402-024-00939-5] PubMed: 38619751
Dual targeting of the androgen receptor and PI3K/AKT/mTOR pathways in prostate cancer models improves antitumor efficacy and promotes cell apoptosis [ Mol Oncol, 2024, 10.1002/1878-0261.13577] PubMed: 38225213
Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy [ Cell Metab, 2022, S1550-4131-2200411-9] PubMed: 36257316
Distinctive molecular features of regenerative stem cells in the damaged male germline [ Nat Commun, 2022, 13(1):2500] PubMed: 35523793
Overexpression of S100A9 in obesity impairs macrophage differentiation via TLR4-NFkB-signaling worsening inflammation and wound healing [ Theranostics, 2022, 12(4):1659-1682] PubMed: 35198063
Cancer genes disfavoring T cell immunity identified via integrated systems approach [ Cell Rep, 2022, 40(5):111153] PubMed: 35926468
Therapeutic Targeting of Stromal-Tumor HGF-MET Signaling in an Organotypic Triple-Negative Breast Tumor Model [ Mol Cancer Res, 2022, 20(7):1166-1177] PubMed: 35348758
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] PubMed: 35326726
Culture and multiomic analysis of lung cancer patient-derived pleural effusions revealed distinct druggable molecular types [ Sci Rep, 2022, 12(1):6345] PubMed: 35428753

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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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