Pictilisib (GDC-0941)

Catalog No.S1065 Batch:S106514

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Technical Data

Formula

C23H27N7O3S2
Molecular Weight 513.64 CAS No. 957054-30-7
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Pictilisib (GDC-0941, RG7321) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.
Targets
p110α [1]
(Cell-free assay)		 p110δ [1]
(Cell-free assay)		 p110β [1]
(Cell-free assay)		 p110γ [1]
(Cell-free assay)		 mTOR [1]
(Cell-free assay)
3 nM 3 nM 33 nM 75 nM 0.58 μM(Ki app)
In vitro 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. GDC-0941 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. GDC-0941 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. [1] GDC-0941 treatment potently inhibits the proliferation of both trastuzumab-sensitive and -insensitive HER2-amplified cells with IC50 of 149-944 nM. GDC-0941 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 that are resistant to trastuzumab due to PTEN loss. [2] GDC-0941 significantly inhibits the growth of HCT116, DLD1 and HT29 cells with GI50 of 1081 nM, 1070 nM and 157 nM, respectively. [3] GDC-0941 inhibits tumor cell proliferation, induces apoptosis and suppresses centroblast population. [4]
In vivo GDC-0941 shows limited microsomal metabolism, resulting in 78% oral bioavailability [5]. Administration of GDC-0941 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%. [1] Oral administration of GDC-0941 at 150 mg/kg/day inhibits the growth of HER2-amplified, trastuzumab-resistant MDA-MB-361.1 xenografts in mice, and significantly delays the tumor progression, in association with potent induced apoptosis in tumors. [2] GDC-0941 (75 mg/kg/day) treatment 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. [4]

Protocol (from reference)

Kinase Assay:

[1]
  • 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 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.
Cell Assay:

[2]
  • Cell lines

    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

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    48 and 72 hours

  • Method

    Cells are exposed to various concentrations of 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.
Animal Study:

[2]
  • Animal Models

    NCR nude mice implanted with MDA-MB-361.1 cells, and SCID, C.B-17/IcrHsd-Prkdcscid mice implanted subcutaneously with BT474-M1 cells

  • Dosages

    ~150 mg/kg/day

  • Administration

    Oral gavage

Customer Product Validation

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]

Data from [J Inves Der, 2010, 131, 495-503]

Selleck's Pictilisib (GDC-0941) has been cited by 485 publications

Neuron-derived neurotensin promotes pancreatic cancer invasiveness and gemcitabine resistance via the NTSR1/Akt pathway [ Am J Cancer Res, 2024, 14(2):448-466] PubMed: 38455426
An oncogenic phenoscape of colonic stem cell polarization [ Cell, 2023, 186(25):5554-5568.e18] PubMed: 38065080
CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications [ Nat Commun, 2023, 14(1):5242] PubMed: 37640697
CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications [ Nat Commun, 2023, 14(1):5242] PubMed: 37640697
SMAD4 maintains the fluid shear stress set point to protect against arterial-venous malformations [ J Clin Invest, 2023, 133(18)e168352] PubMed: 37490341
SMAD4 maintains the fluid shear stress set point to protect against arterial-venous malformations [ J Clin Invest, 2023, e168352] PubMed: 37490341
Revisiting the role of endogenous STAT3 in HPV-positive cervical cancer cells [ J Med Virol, 2023, 95(11):e29230] PubMed: 38009614
Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition [ Cancer Res, 2023, 83(2):316-331] PubMed: 36409827
Loss of Dnmt3a impairs hematopoietic homeostasis and myeloid cell skewing via the PI3Kinase pathway [ JCI Insight, 2023, 8(9)e163864] PubMed: 36976647
Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans [ JCI Insight, 2023, 8(22)e164672] PubMed: 37856221

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