1. PI3K/Akt/mTOR
  2. PI3K
    mTOR

GDC-0980 (Synonyms: GNE 390; RG 7422)

Cat. No.: HY-13246 Purity: 99.13%
Data Sheet SDS Handling Instructions

GDC-0980 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, and also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases.

For research use only. We do not sell to patients.
GDC-0980 Chemical Structure

GDC-0980 Chemical Structure

CAS No. : 1032754-93-0

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $143 In-stock
10 mg $130 In-stock
50 mg $380 In-stock
100 mg $650 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

GDC-0980 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, and also a mTOR inhibitor with Ki of 17 nM in a cell-free assay, and highly selective versus other PIKK family kinases.

IC50 & Target

IC50: 5 nM (PI3Kα), 27 nM (PI3Kβ), 7 nM (PI3Kδ), 14 nM (PI3Kγ)

In Vitro

GDC-0980 is remarkably selective for several other members of the closely related PIKK family kinases: C2alpha IC50=1300 nM; C2beta IC50=7 94 nM; VPS34 IC50=2000 nM; PI4Kalpha >10 μM; PI4Kbeta >10 μM; DNA-PK Kiapp=623 nM, respectively[1]. A recent study shows that GDC-0980 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

GDC-0980 (1 mg/kg, p.o.) demonstrats significant efficacy in mouse xenografts and is currently in phase I clinical trials for cancer. Clearance and PPB are low, and GDC-0980 shows dose-proportional exposure from 5 mg/kg dosed in PEG to 50 mg/kg dosed in suspension in MCT, a finding attributed partially to the compound’s good solubility[1]. GDC-0980 (5 mg/kg, p.o.) results in greater than 50% TGI in 15 of the 20 xenograft models. The difference in tumor response to GDC-0980 treatment correlates with the duration of knockdown of pAkt/tAkt[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT01442090 Genentech, Inc. Renal Cell Carcinoma October 2011 Phase 2
NCT01455493 Genentech, Inc. Endometrial Carcinoma December 2011 Phase 2
NCT00854126 Genentech, Inc. Non-Hodgkin's Lymphoma, Solid Cancers May 2009 Phase 1
NCT00854152 Genentech, Inc. Non-Hodgkin's Lymphoma, Solid Cancers March 2009 Phase 1
NCT01487239 Genentech, Inc. Healthy Volunteer December 2011 Phase 1
NCT01473316 Genentech, Inc. Healthy Volunteer November 2011 Phase 1
NCT01254526 Genentech, Inc. Breast Cancer December 2010 Phase 1
NCT01437566 Genentech, Inc. Breast Cancer October 2011 Phase 2
NCT01485861 Genentech, Inc. Prostate Cancer January 11, 2012 Phase 1|Phase 2
NCT01332604 Genentech, Inc. Solid Cancers July 2011 Phase 1
NCT01287091 Genentech, Inc. Healthy Volunteer October 2010 Phase 1
NCT01301716 Genentech, Inc. Solid Cancers September 2011 Phase 1
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.0056 mL 10.0281 mL 20.0562 mL
5 mM 0.4011 mL 2.0056 mL 4.0112 mL
10 mM 0.2006 mL 1.0028 mL 2.0056 mL
Kinase Assay
[2]

Ten centimeter square dishes are seeded with 2 million cells in a volume of 10 mL followed by incubation at 37°C under 5% CO2 overnight (appr 16 hours). Cells are treated with the indicated concentration of GDC-0941, GDC-0980, or mTOR1/2 inhibitor for the time indicated. Following treatment, cells are washed with cold PBS and lysed in 1X Cell Extraction Buffer, 1 mM PMSF, and Phosphatase Inhibitor Cocktails 1 and 2 are all needed. Protein concentration is determined using the Pierce BCA Protein Assay Kit. For immunoblots, equal protein amounts are separated by electrophoresis through NuPage Bis-Tris 10% gradient gels; proteins are transferred onto polyvinylidene difluoride membranes using the Criterion system and protocol. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

GDC-0980 is dissolved in DMSO.

Three hundred and eighty-four-well plates are seeded with 2,000 cells/well in a volume of 54 μL per well followed by incubation at 37°C under 5% CO2 overnight (appr 16 hours). Compounds are diluted in dimethyl sulfoxide to generate the desired stock concentrations then added in a volume of 6 μL per well. All treatments are tested in quadruplicate. After 4 days incubation, relative numbers of viable cells are estimated using CellTiter-Glo and total luminescence is measured on a Wallac Multilabel Reader. The concentration of drug resulting in 50% inhibition of cell viability (IC50) or 50% maximal effective concentration (EC50) is determined using Prism software. For cell lines that failed to achieve an IC50 the highest concentration tested (20 μM) is listed. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

GDC-0980 is dissolved in 0.5% methylcellulose with 0.2% Tween-80 (MCT)

Human prostate cancer PC3 cells are resuspended in Hank’s Balanced Salt Solution and 3×106 cells implanted subcutaneously into the right hind flank of athymic nu/nu (nude) mice. Tumors are monitored until they reach a mean tumor volume of 150-200 mm3 prior to the initiation of dosing. MCF7.1 cells resuspended in a 1:1 mixture of Hank’s Buffered Salt Solution and Matrigel Basement Membrane Matrix are 5×106 subcutaneously implanted into the right hind flank of athymic nu/nu (nude) mice. Prior to cell inoculation, 17β-estradiol (0.36 mg/pellet, 60-day release, no. SE-121) are implanted into the dorsal shoulder blade area of each nude mouse. After implantation of cells, tumors are monitored until they reach a mean tumor volume of 250-350 mm3 prior to initiating dosing. Compound 2 is dissolved in 0.5% methylcellulose with 0.2% Tween-80 (MCT). Female nude (nu/nu) mice that are 6-8 weeks old and weighed 20-30 g are obtained from Charles River Laboratories. Tumor bearing mice are dosed daily for 14-21 days depending on the xenograft model with 100 μL of vehicle (MCT) or test agent orally. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

498.6

Formula

C₂₃H₃₀N₈O₃S

CAS No.

1032754-93-0

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

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

Purity: 99.13%

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Product Name:
GDC-0980
Cat. No.:
HY-13246
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