GDC-0152

For research use only.

Catalog No.S7010

19 publications

GDC-0152 Chemical Structure

CAS No. 873652-48-3

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.

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 NF7O[YJHfW6ldHnvckBie3OjeR?= MoX6NU02OCEQvF2= NVu4ZZpJOiCq MkPSTY5pcWKrdHnvckBw\iCIbHHnMZRi\2enZDDYTWFRKEKLUkOg[I9u[WmwIHLpcoRqdmdidH:gZ2lCWDFiZYjwdoV{e2WmIHnuJIh2dWGwIFjFT|I6O1RiY3XscJMh[XRiMTD0c{A2OCC3TTDh[pRmeiB{IHjyd{BjgSCrbX31co9xemWlaYDpeIF1cW:w MlT1NlI1OTN6NkO=
SK-MEL28 cells MU\GeY5kfGmxbjDhd5NigQ>? M2PYPFAvPSEQvF2= M{nHTGlvcGmkaYTpc44hd2ZiTVytTWFRKGKrbnTpcochfG9iU33hfEBmgHC{ZYPz[YQhcW5iZ3XtZ4l1[WKrbnWgZY5lKHqYQXSgeJJm[XSnZDDoeY1idiCVSz3NSWwzQCClZXzsd{BifCByLkWgeW0h[nliaX3teY5weHKnY3nwbZRifGmxbh?= MmjqNlI1OTN6NkO=
A2058 cells M3y3eGZ2dmO2aX;uJIF{e2G7 NEXyR4IyPSCvaX7z Mk\3TY5lfWO2aX;uJI9nKHC{b4TlZZNwdWGuIHTl[5Ji\GG2aX;uJI9nKGOLQWCxJIlvKGi3bXHuJGEzODV6IHPlcIx{KGGodHXyJFE2KG2rboOgZpkhcW2vdX7vZoxwfHSrbne= NYXQN49XOjJ2MUO4OlM>
MDA-MB-231 cells NX76WXNES3m2b4TvfIlkcXS7IHHzd4F6 M3TEPVczKGh? NWrXd|BnS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUSDLV3CMVI{OSClZXzsd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDseY1qdmW|Y3XueEBie3OjeR?= NXzRVXJOOjJ2MUO4OlM>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
cIAP1 / cIAP2 / XIAP / ML-IAP ; 

PubMed: 27490930     


Expression levels of cIAP1, cIAP2, XIAP and ML-IAP were analyzed by western blotting. Cell lines were treated with 1 μM of GDC-0152. U87MG and GL261 were treated for 72 h and GBM6 and GBM9 cell lines for 8 days. In all GBM cell lines GDC-0152 decreased IAP expression. Expression level of β-actin served as loading control. A representative experiment of three experiments is shown

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

Kinase Assay:[1]
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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]
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  • 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.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: human-tumor xenograft mouse models of MDA-MB-231 breast cancer
  • Dosages: 10, 50, or 100 mg/kg
  • Administration: oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 99 mg/mL (198.54 mM)
Ethanol 99 mg/mL (198.54 mM)
Water 3 mg/mL (6.01 mM)
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

* 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.

Chemical Information

Molecular Weight 498.64
Formula

C25H34N6O3S

CAS No. 873652-48-3
Storage powder
in solvent
Synonyms N/A
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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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

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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IAP Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID