1. PI3K/Akt/mTOR
    Autophagy
  2. PI3K
    Autophagy

GDC-0941 (Synonyms: Pictilisib)

Cat. No.: HY-50094 Purity: 99.52%
Data Sheet SDS Handling Instructions

GDC-0941 is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).

For research use only. We do not sell to patients.
GDC-0941 Chemical Structure

GDC-0941 Chemical Structure

CAS No. : 957054-30-7

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $55 In-stock
10 mg $50 In-stock
50 mg $75 In-stock
100 mg $120 In-stock
200 mg $210 In-stock
500 mg   Get quote  
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Other Forms of GDC-0941:

    GDC-0941 purchased from MCE. Usage Cited in: Cancer Discov. 2012 May;2(5):425-33.

    Effects of KIN-193, GDC-0941, PIK-75 and IC87114 on AKT phosphorylation in PTEN-deficient cell lines as indicated. Representative western blots are shown. Bar graphs represent mean ± SD of western blot quantitations of AKTT308 (n=3).

    GDC-0941 purchased from MCE. Usage Cited in: Cell Metab. 2012 Mar 7;15(3):382-94.

    Effect of the indicated PI3K inhibitors on pre-brown adipocytes. Cultures are treated with the inhibitors at the indicated concentrations (μM) for 4 h. Protein levels (top) and mRNA levels (bottom) of the indicated proteins and genes, respectively, are analyzed. Assays are performed in triplicate cultures. Values represent mean ± sd, and statistical significance is determined by the two-tailed Student’s t-test. *p<0.05, **p<0.01.

    GDC-0941 purchased from MCE. Usage Cited in: Sci Transl Med. 2013 Jul 31;5(196):196ra99.

    Sensitivity to GDC-0941 in parental MDA453 and T47D and BYL719-resistant MDA453R and T47DR cells. Protein lysates are isolated after 24 hours of treatment with 1 μM GDC-0941 and probed against the indicated proteins.

    GDC-0941 purchased from MCE. Usage Cited in: Sci Transl Med. 2013 Jul 31;5(196):196ra99.

    Apoptosis and PI3K/Akt/mTOR pathway inhibition in cells treated with BYL719, RAD001, or the combination. Protein lysates from HCC1954 and JIMT-1 cells treated for 18 hours with 0.5 μM BYL719, 1 nM RAD001 or the combination are analyzed by immunoblotting against the indicated proteins. Data are shown as mean ± SEM. p-value is calculated using two-sided student’s t-test.

    GDC-0941 purchased from MCE. Usage Cited in: Cancer Res. 2014 Jan 1;74(1):15-23.

    Differential responses of Pten Lkb1-deficient endometrial tumors to inhibitors targeting PI3K and/or mTOR. Mice bearing transplanted Pten Lkb1-deficient endometrial tumors are treated with indicated drugs for 3 days and sacrificed three hours after their dose on day 3 of treatment; their tumors are isolated and tumor lysates are immunoblotted with the indicated antibodies.

    GDC-0941 purchased from MCE. Usage Cited in: Cancer Res. 2014 Jan 1;74(1):15-23.

    Ectopic expression of LKB1 renders PTEN LKB1-deficient endometrial cancer cells susceptible to PI3K inhibition. Western blot analysis of pS6RP (Ser235/236) and p4EBP1(Ser65) in ETN-1 and HEC108 cells with stable expression of vector or flag- tagged LKB1. Cell lysates were harvested 24 hours after GDC-0941 treatment.

    GDC-0941 purchased from MCE. Usage Cited in: Nat Commun. 2015 Oct 7;6:8501.

    Western blot analysis of Akt signalling in whole BM cells at 7 DPI. Freshly isolated BM cells are treated with DMSO, BYL719, KIN193, GS1101 or NVSPI35 at the 1-μM dose for 2 h (n=6) for each treatment.

    GDC-0941 purchased from MCE. Usage Cited in: Oncogene. 2016 Jun 9;35(23):2961-70.

    The combined use of MEK162 with HER kinase inhibitor Lapatinib, almost completely abolishes MAPK signaling as evidenced by diminished phospho-Erk levels. Western blot analyses of ERK signaling in tumor transplants from mice treated as indicated. Three hours after their dose on day four of treatment, the mice are sacrificed for analysis. Vinculin is used as a loading control.

    GDC-0941 purchased from MCE. Usage Cited in: Oncogene. 2016 Jun 9;35(23):2961-70.

    Western blot analysis of p-AKT(T308), p-AKT(S473) and p-ERK in transplanted NIC+PIK3CAH1047R tumors treated as indicated. Transplants of NIC+PIK3CAH1047R primary mammary tumors are first established in immunodeficient nude mice maintained on Doxycycline. Treatment starts when tumor transplants reach 500 mm3. DOX On, on Doxycycline; DOX Off, Doxycycline withdrawal. Lapatinib, 100mg/kg/day, p.o; GDC-0941, 120mg/kg/ day, p.o. Tumo

    GDC-0941 purchased from MCE. Usage Cited in: Nat Commun. 2016 Feb 2;7:10438.

    Western blot illustrating the effect of PI3K inhibitors on p21 protein levels in MEFs. Cells are treated for 24 hours with the indicated concentrations of the different drugs.

    GDC-0941 purchased from MCE. Usage Cited in: Oncotarget. 2016 May 31;7(22):32641-51.

    The well-established PI3Kδ specific inhibitor, CAL-101, shows similar effects as PI3KD-IN-015 with an EC50 of 2.3 nM against PI3Kδ and over 1000-fold less potent against the other three isoforms. Determination of CAL-101 inhibitory activities against PI3Kα, β, δ and γ in cellular background.

    GDC-0941 purchased from MCE. Usage Cited in: Oncotarget. 2016 Aug 16;7(33):53515-53525.

    PI3KD/V-IN-01 affects autophagy HeLa cells are treated with different concentrations of PI3KD/V-IN-01, VPS34-IN-1, GDC-0941 or CAL-101 for 16 hours before they are fixed and stained for the autophagy marker LC3B.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    GDC-0941 is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).

    IC50 & Target

    IC50: 3 nM (PI3Kα), 3 nM (PI3Kδ)

    In Vitro

    GDC-0941 and docetaxel reduce tumor cell viability by 80% or greater in the breast cancer cell lines than single-agent treatment. GDC-0941 inhibits Akt phosphorylation and downstream targets of Akt signaling such as pPRAS40 and pS6 in Hs578T1.2 (PI3Kα wild-type), MCF7-neo/HER2 (PI3Kα-mutant), and MX-1 (PTEN-null) tumor models. GDC-0941 decreases the time of docetaxel-induced mitotic arrest prior to apoptosis[1]. GDC-0941 shows a high efficacy of antitumor activity in two gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, A549 and H460. GDC-0941 is highly efficacious in combination with U0126 in inducing cell growth inhibition, G0-G1 arrest and cell apoptosis. H460 cells with activating mutations of PIK3CA are relatively more sensitive to GDC-0941 than A549 cells with wild-type PIK3CA[3]. GDC-0941 reduces PI3K pathway activity in both cell lines, illustrated by decreased pAK. GDC-0941 significantly reduces secreted VEGF detected in the medium after hypoxic/anoxic exposure in all cells[4].

    In Vivo

    GDC-0941 (150 mg/kg, p.o.) leads to tumor stasis in MCF7-neo/HER2-bearing animals model. GDC-0941 and docetaxel result in tumor regressions during the treatment period leading to enhanced antitumor responses[1]. Tumours in the GDC-0941-treated mice show a marked non-linear shrinkage, and when the GDC-0941 treatment ceased, the tumours in the test cohort mice grow again[2]. GDC-0941 (25 or 50 mg/kg) reduces tumor growth and PI3K and HIF-1 pathway activity in eGFP-FTC133 tumor-bearing mice[4].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT00876109 Genentech, Inc. Solid Cancers October 2007 Phase 1
    NCT01740336 Genentech, Inc. Breast Cancer February 6, 2013 Phase 2
    NCT00876122 Genentech, Inc. Non-Hodgkin's Lymphoma, Solid Cancers March 2008 Phase 1
    NCT00975182 Genentech, Inc. Non-Squamous Non-Small Cell Lung Cancer, Solid Cancers September 2009 Phase 1
    NCT00999128 Genentech, Inc. Healthy Volunteers October 26, 2009 Phase 1
    NCT01240226 Genentech, Inc. Healthy Volunteer November 2010 Phase 1
    NCT01437566 Genentech, Inc. Breast Cancer October 2011 Phase 2
    NCT00974584 Genentech, Inc. Non-Squamous Non-Small Cell Lung Cancer October 2009 Phase 1
    NCT00928330 Genentech, Inc. Metastatic Breast Cancer July 2009 Phase 1
    NCT01474668 Genentech, Inc. Healthy Volunteer October 2011 Phase 1
    NCT02092831 Genentech, Inc. Healthy Volunteer April 2014 Phase 1
    NCT00996892 Genentech, Inc. Solid Tumors November 2009 Phase 1
    NCT00960960 Genentech, Inc. Breast Cancer August 2009 Phase 1
    NCT01493843 Genentech, Inc. Non-Small Cell Lung Cancer January 20, 2012 Phase 2
    NCT02389842 Royal Marsden NHS Foundation Trust|Institute of Cancer Research, United Kingdom|Roche Pharma AG|Pfizer Advanced Solid Tumours|Breast Cancer February 2015 Phase 1
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    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 1.9469 mL 9.7344 mL 19.4689 mL
    5 mM 0.3894 mL 1.9469 mL 3.8938 mL
    10 mM 0.1947 mL 0.9734 mL 1.9469 mL
    Cell Assay
    [1]

    Cells are treated at EC50 concentrations of GDC-0941, docetaxel, or both for 4 or 24 hours and lysed in 1×Cell Extraction Buffer supplemented with protease inhibitors and Phosphatase Inhibitor Cocktails 1 and 2. Protein concentrations are determined using the Pierce BCA Protein Assay Kit. For immunoblots, equal amounts of protein are separated by electrophoresis through NuPAGE Bis-Tris 10% gradient gels, transferred onto polyvinylidene difluoride membranes using the Criterion system, and probed with monospecific primary antibodies. Specific antigen-antibody interactions are detected with IRDye 680 or IRDye 800 infrared secondary antibodies using a LI-COR imaging system. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    GDC-0941 is formulated in MCT (0.5% methylcellulose, 0.2% Tween-80).

    Female nu/nu mice are inoculated subcutaneously with MCF7-neo/HER2 or MX-1 breast cancer cells. When tumors reach a mean volume of 200 to 250 mm3, animals are size-matched and distributed into groups consisting of 10 animals per group. Docetaxel formulated in 3% EtOH, 97% saline is administered intravenously once weekly. GDC-0941, formulated in MCT (0.5% methylcellulose, 0.2% Tween-80) is dosed orally and daily. MAXF1162 is an 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 is calculated as follows: tumor size (mm3)=(longer measurement×shorter measurement2) × 0.5. Tumor sizes are recorded twice weekly over the course of a study. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    513.64

    Formula

    C₂₃H₂₇N₇O₃S₂

    CAS No.

    957054-30-7

    Storage

    Please store the product under the recommended conditions in the Certificate of Analysis.

    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 29 mg/mL

    GDC-0941 is prepared in vehicel (0.1% methylose, 0.1% Tween 80)[5].
    GDC-0941 is dissolved in 0.5% methylcellulose/0.2% Tween 80[6].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

    Purity: 99.52%

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    Product Name:
    GDC-0941
    Cat. No.:
    HY-50094
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