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GDC-0152

Cat. No. M2138
GDC-0152 Structure
Size Price Availability Quantity
10mg USD 180 In stock
50mg USD 580 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

GDC-0152 is a small-molecule IAP antagonist that triggers tumor cell apoptosis by selectively antagonizing IAPs. GDC-0152 binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with K(i) values of 28, 14, 17, and 43 nM, respectively. GDC-0152 inhibits tumor growth when dosed orally in the MDA-MB-231 breast cancer xenograft model. GDC-0152 induces activation of caspase-3/7, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. GDC-0152 induces NF-κB transcriptional activity leading to expression of several chemokines and cytokines, of which tumor necrosis factor alpha (TNF-α) is the most important for single-agent tumor activity.

Protocol
Cell Experiment
Cell lines MDA-MB-231, mormal HMECs cell lines
Preparation method Cell Viability and Caspase Activation Assays Human breast carcinoma MDA-MB-231 were obtained from ATCC. Normal human mammary epithelial cells (HMECs) were obtained from Cambrex Corp.. Cells were dissociated from tissue culture flasks by incubation with Accutase® (Innovative Cell Technology Inc.) for 5–10 minutes. Detached cells were washed with phosphate-buffered saline (PBS) and were resuspended in assay media (MDA-MB-231 cells: RPMI1640 supplemented with 10% fetal bovine serum [Sigma-Aldrich] and 2 mM L-glutamine [GlutaMAX-1; Gibco/Invitrogen Corp.]) or culture media (HMECs: MEBM® with MEGM SingleQuots® provided by Cambrex Corp.). Cells were placed in tissue culture-treated, white-wall (Corning, Inc.) or black-wall (PE Biosystems), clear-bottom, 96-well plates at 1 × 104 cells/well in a volume of 50 μL. The plates were incubated at 37°C and 5% CO2 overnight, the media was removed, and 1 or it's enantiomer were added in assay media. Cells cultured in white-wall, clear-bottom plates were incubated at 37°C and 5% CO2 for 3 days before cell viability was measured using the CellTiter-Glo® luminescent cell viability assay kit (Promega Corp.) according to the manufacturer's instructions. Cells seeded in black-wall, clear-bottom plates were incubated at 37°C and 5% CO2 for 3–24 hours before caspase-3 and -7 homogeneous activities were assessed using the Apo-ONE® caspase-3/7 assay kit (Promega Corp.) according to the manufacturer's instructions.
Concentrations
Incubation time 3 days
Animal Experiment
Animal models Human breast cancer MDA-MB-231 cells tumor xenograft mice
Formulation PBS
Dosages 4.0 ml/kg
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 498.64
Formula C25H34N6O3S
CAS Number 873652-48-3
Purity >99%
Solubility DMSO 90 mg/mL
Ethanol 90 mg/mL
Storage at -20°C
References

Toxicity profile of small-molecule IAP antagonist GDC-0152 is linked to TNF-α pharmacology.
Erickson RI, et al. Toxicol Sci. 2013 Jan;131(1):247-58. PMID: 22956632.

Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152).
Flygare JA, et al. J Med Chem. 2012 May 10;55(9):4101-13. PMID: 22413863.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: GDC-0152 supplier, IAP, inhibitors

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