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GDC-0152 IAP antagonist

Cat.No.S7010

GDC-0152 is a potent antagonist of XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with K_i 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.

Chemical Structure

Molecular Weight: 498.64

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.73%

99.73

Related Targets	Apoptosis related Ras STAT TNF-alpha Bcl-2 Caspase PD-1/PD-L1 Ferroptosis p53 RIP kinase c-RET MDM2/MDMX Myc OXPHOS PERK FKBP Thymidylate Synthase ABC Transporter Heme Oxygenase PFKFB PKD Survivin Pyroptosis ASK Bcl-6 Nur77 DAPK TRADD TACE Cuproptosis
Related Products	Birinapant (TL32711) BV-6 LCL161 Xevinapant (AT406) AZD5582 SM-164 Tolinapant (ASTX660) XIAP Antibody [J5B21] c-IAP1 Antibody [F9A20] cIAP1 Antibody [B13P10] c-IAP2 Antibody [J16G5]

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description
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
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
A2058 cells	Function assay		15 mins	Induction of proteasomal degradation of cIAP1 in human A2058 cells after 15 mins by immunoblotting
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
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	498.64	Formula	C₂₅H₃₄N₆O₃S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	873652-48-3	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C(=O)NC3=C(N=NS3)C4=CC=CC=C4)NC

Solubility

In vitro
Batch:

DMSO : 99 mg/mL (198.54 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 99 mg/mL

Water : 3 mg/mL

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (10.03mM)	Taking the 1 mL working solution as an example, add 300 μL of clarified propylene glycol stock solution of 16.67 mg/ml to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

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.

Mechanism of Action

Targets/IC₅₀/Ki	MLXBIR3SG ^[1] (Cell-free assay) 14 nM(Ki) cIAP1-BIR3 ^[1] (Cell-free assay) 17 nM(Ki) XIAP-BIR3 ^[1] (Cell-free assay) 28 nM(Ki) cIAP2-BIR3 ^[1] (Cell-free assay) 43 nM(Ki) XIAP-BIR2 ^[1] (Cell-free assay) 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, this compound 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 this chemical. It 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). This compound is found to activate caspases 3 and 7 in a dose- and time-dependent manner. It 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
Kinase Assay	Inhibition constants ( K_i ) 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. K_i values for the antagonists are determined from the IC50 valued.
In vivo	GDC-0152 has moderate predicted hepatic clearance based on metabolic stability assays conducted using human liver microsomes. Plasma−protein binding of this compound 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%). It 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 this chemical is achieved with a C _max of 53.7 μM and AUC of 203.5 h•μM. ^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/22413863/

Applications

Methods	Biomarkers	Images	PMID
Western blot	cIAP1 / cIAP2 / XIAP / ML-IAP		27490930

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00977067	Terminated	Solid Cancers	Genentech Inc.	June 2007	Phase 1

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