GDC-0152

Catalog No.S7010

For research use only.

GDC-0152 is a potent antagonist of XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 28 nM, 14 nM, 17 nM and 43 nM in cell-free assays, respectively; less affinity shown to cIAP1-BIR2 and cIAP2-BIR2. Phase 1.

GDC-0152 Chemical Structure

CAS No. 873652-48-3

Selleck's GDC-0152 has been cited by 19 publications

Purity & Quality Control

Choose Selective IAP Inhibitors

Biological Activity

Description GDC-0152 is a potent antagonist of XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 28 nM, 14 nM, 17 nM and 43 nM in cell-free assays, respectively; less affinity shown to cIAP1-BIR2 and cIAP2-BIR2. Phase 1.
Targets
MLXBIR3SG [1]
(Cell-free assay)
cIAP1-BIR3 [1]
(Cell-free assay)
XIAP-BIR3 [1]
(Cell-free assay)
cIAP2-BIR3 [1]
(Cell-free assay)
XIAP-BIR2 [1]
(Cell-free assay)
14 nM(Ki) 17 nM(Ki) 28 nM(Ki) 43 nM(Ki) 112 nM(Ki)
In vitro

GDC-0152 can block protein−protein interactions that involve IAP proteins and pro-apoptotic molecules. Using transiently transfected HEK293T cells, GDC-0152 is shown to disrupt XIAP binding to partially processed caspase-9 and to disrupt the association of ML-IAP, cIAP1, and cIAP2 with Smac. In melanoma SK-MEL28 cells, the endogenous association of ML-IAP and Smac is effectively also abolished by GDC-0152. GDC-0152 lead to a decrease in cell viability in the MDA-MB-231 breast cancer cell line, while having no effect on normal human mammary epithelial cells (HMEC). GDC-0152 is found to activate caspases 3 and 7 in a dose- and time-dependent manner. GDC-0152 is shown to induce rapid degradation of cIAP1 in A2058 melanoma cells. It effectively induces degradation of cIAP1 at concentrations as low as 10 nM, consistent with its affinity for cIAP1.

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293T cells M3PIZ2Z2dmO2aX;uJIF{e2G7 MWKxMVUxKM7:TR?= NIrRXpgzKGh? MYTJcohq[mm2aX;uJI9nKE[uYXeteIFo\2WmIGjJRXAhSkmUMzDkc41icW5iYnnu[Ilv\yC2bzDjTWFROSCneIDy[ZN{\WRiaX6gbJVu[W5iSFXLNlk{XCClZXzsd{BifCBzIITvJFUxKHWPIHHmeIVzKDJiaILzJIJ6KGmvbYXuc5Bz\WOrcHn0ZZRqd25? MUmyNlQyOzh4Mx?=
SK-MEL28 cells NXjYSWtYTnWwY4Tpc44h[XO|YYm= Ml65NE42KM7:TR?= MVXJcohq[mm2aX;uJI9nKE2OLVnBVEBjcW6maX7nJJRwKFOvYYig[ZhxemW|c3XkJIlvKGenbXPpeIFjcW6nIHHu[EB7XkGmIITy[YF1\WRiaIXtZY4hW0tvTVXMNlgh[2WubIOgZZQhOC53IIXNJIJ6KGmvbYXuc5Bz\WOrcHn0ZZRqd25? M3GzR|IzPDF|OE[z
A2058 cells Mn3CSpVv[3Srb36gZZN{[Xl? MX:xOUBucW6| NWfqdI16UW6mdXP0bY9vKG:oIIDyc5Rm[XOxbXHsJIRm\3KjZHH0bY9vKG:oIHPJRXAyKGmwIHj1cYFvKEF{MEW4JINmdGy|IHHmeIVzKDF3IH3pcpMh[nliaX3teY5w[myxdITpcoc> Mn;jNlI1OTN6NkO=
MDA-MB-231 cells NYnxUXNRS3m2b4TvfIlkcXS7IHHzd4F6 NGLYbIg4OiCq M3\vXmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1FSS2PQj2yN|Eh[2WubIOgZZN{\XO|ZXSgZZMh\GWlcnXhd4UhcW5iY3XscEB3cWGkaXzpeJkh[W[2ZYKgO|IhcHK|IHL5JGNmdGyWaYTldk1IdG9ibIXtbY5me2OnboSgZZN{[Xl? M1TmdVIzPDF|OE[z
Assay
Methods Test Index PMID
Western blot cIAP1 / cIAP2 / XIAP / ML-IAP 27490930
In vivo GDC-0152 has moderate predicted hepatic clearance based on metabolic stability assays conducted using human liver microsomes. Plasma−protein binding of GDC-0152 is moderate and comparable among mice (88−91%), rats (89−91%), dogs (81−90%), monkeys (76−85%), and humans (75−83%) over the range of concentrations investigated (0.1−100 μM); higher plasma−protein binding is observed in rabbits (95−96%). GDC-0152 does not preferentially distribute to red blood cells with blood−plasma partition ratios ranging from 0.6 to 1.1 in all species tested. The pharmacokinetics for GDC-0152 is achieved with a C max of 53.7 μM and AUC of 203.5 h•μM. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Fluorescence polarization-based competition assay:

    Inhibition constants ( Ki ) for the antagonists are determined by addition of the IAP protein constructs to wells containing serial dilutions of the antagonists or the peptide AVPW, and the Hid-FAM probe or AVP-diPhe-FAM probe, as appropriate, in the polarization buffer. Samples are read after a 30-minute incubation. Fluorescence polarization values are plotted as a function of the antagonist concentration, and the IC50 values are obtained by fitting the data to a 4-parameter equation using software. Ki values for the antagonists are determined from the IC50 valued.

Cell Research:[1]
  • Cell lines: MDA-MB-231, Normal human mammary epithelial cells (HMECs)
  • Concentrations: ~1 μM
  • Incubation Time: 72 h
  • Method: MDA-MB-231 breast carcinoma cells and HMECs are treated with the indicated concentrations of GDC-0152. Cell death is assessed using the CellTiter-Glo luminescent cell viability assay 72 h following the start of treatment.
Animal Research:[1]
  • Animal Models: human-tumor xenograft mouse models of MDA-MB-231 breast cancer
  • Dosages: 10, 50, or 100 mg/kg
  • Administration: oral gavage

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% propylene glycol, 5% Tween 80, 65% D5W
For best results, use promptly after mixing.

5 mg/mL

Chemical Information

Molecular Weight 498.64
Formula

C25H34N6O3S

CAS No. 873652-48-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C(=O)NC3=C(N=NS3)C4=CC=CC=C4)NC

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00977067 Terminated Drug: GDC-0152 Solid Cancers Genentech Inc. June 2007 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-11-29)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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