[CAS NO. 873652-48-3] GDC-0152

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PRODUCTS SPECIFICATIONS [873652-48-3]

Catalog

HY-13638

Brand

MCE

CAS

873652-48-3

DESCRIPTION [873652-48-3]

Overview

MDL	MFCD26142660
Molecular Weight	498.64
Molecular Formula	C25H34N6O3S
SMILES	O=C(N1[C@H](C(NC2=C(C3=CC=CC=C3)N=NS2)=O)CCC1)[C@H](C4CCCCC4)NC([C@H](C)NC)=O

For research use only. We do not sell to patients.

9 Publications Citing Use of MCE

Summary

GDC-0152 is a potent IAPs inhibitor, and binds to the BIR3 domains of XIAP , cIAP1 , cIAP2 and the BIR domain of ML-IAP with K _i values of 28 nM, 17 nM, 43 nM and 14 nM, respectively.

IC50 & Target

Ki: 28 nM (XIAP BIR3), 14 nM (MLIAP-BIR3), 17 nM (cIAP1-BIR3), 43 nM (cIAP2-BIR3)

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 also effectively abolished by GDC-0152. GDC-0152 leads 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 ^[1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT00977067	Genentech, Inc.	Solid Cancers	June 2007	Phase 1

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

In Vitro:

Ethanol : 50 mg/mL ( 100.27 mM ; Need ultrasonic)

DMSO : 50 mg/mL ( 100.27 mM ; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.0055 mL	10.0273 mL	20.0545 mL
5 mM	0.4011 mL	2.0055 mL	4.0109 mL
10 mM	0.2005 mL	1.0027 mL	2.0055 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 2.5 mg/mL (5.01 mM); Clear solution
2.

Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (5.01 mM); Clear solution
3.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 2.5 mg/mL (5.01 mM); Clear solution

* All of the co-solvents are available by MCE.

References

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