Home Apoptosis IAP antagonist GDC-0152 For research use only.

GDC-0152

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

GDC-0152 Chemical Structure

CAS No. 873652-48-3

Purity & Quality Control

GDC-0152 Related Products

Signaling Pathway

IAP Signaling Pathways

IAP Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293T cells Function assay 1-50 μM 2 h Inhibition of Flag-tagged XIAP BIR3 domain binding to cIAP1 expressed in human HEK293T cells at 1 to 50 uM after 2 hrs by immunoprecipitation 22413863
SK-MEL28 cells Function assay 0.5 μM Inhibition of ML-IAP binding to Smax expressed in and zVAd treated human SK-MEL28 cells at 0.5 uM by immunoprecipitation 22413863
A2058 cells Function assay 15 mins Induction of proteasomal degradation of cIAP1 in human A2058 cells after 15 mins by immunoblotting 22413863
MDA-MB-231 cells Cytotoxicity assay 72 h Cytotoxicity against human MDA-MB-231 cells assessed as decrease in cell viability after 72 hrs by CellTiter-Glo luminescent assay 22413863
Click to View More Cell Line Experimental Data

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
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.
Kinase Assay 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 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot cIAP1 / cIAP2 / XIAP / ML-IAP 27490930
In Vivo
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]
Animal Research Animal Models human-tumor xenograft mouse models of MDA-MB-231 breast cancer
Dosages 10, 50, or 100 mg/kg
Administration oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00977067 Terminated
Solid Cancers
Genentech Inc.
 June 2007 Phase 1

Chemical Information & Solubility

Molecular Weight 498.64 Formula

C25H34N6O3S
CAS No. 873652-48-3 SDF Download GDC-0152 SDF
Smiles CC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C(=O)NC3=C(N=NS3)C4=CC=CC=C4)NC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 99 mg/mL ( (198.54 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 99 mg/mL

Water : Insoluble


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In vivo
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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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