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Tolinapant (ASTX660) IAP antagonist

Name: Tolinapant (ASTX660)
Brand: Selleck Chemicals
SKU: S8681
Availability: InStock
Rating: 5 (4 reviews)

Cat.No.S8681

Tolinapant (ASTX660) is a potent, non-peptidomimetic antagonist of cIAP1/2 and XIAP that inhibits the interactions between a SMAC-derived peptide and the BIR3 domains of XIAP (BIR3-XIAP) and cIAP1 (BIR3-cIAP1) with IC50 values less than 40 and 12 nmol/L, respectively.

Chemical Structure

Molecular Weight: 539.68

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Quality Control

Batch: S868101 DMSO]100 mg/mL]false]Ethanol]100 mg/mL]false]Water]Insoluble]false Purity: 99.75%

Cited in Nature Medicine for its top-tier quality
COA
NMR
SDS
Datasheet

99.75

Related Targets	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Other IAP Inhibitors	SM-164 Birinapant (TL32711) BV6 LCL161 Xevinapant (AT406) GDC-0152 AZD5582

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (185.29 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection 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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.26mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.625mg/ml (1.16mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

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.

Chemical Information, Storage & Stability

Molecular Weight	539.68	Formula	C₃₀H₄₂FN₅O₃	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1799328-86-1	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1CN(C(CN1)CN2CCOCC2C)CC(=O)N3CC(C4=C3C=C(C(=N4)CO)CC5=CC=C(C=C5)F)(C)C

Mechanism of Action

Targets/IC₅₀/Ki	cIAP2 cIAP1 (Cell-free assay) 12 nM XIAP (Cell-free assay) 40 nM
In vitro	Tolinapant (ASTX660) induces proteasomal degradation of cIAP1 and 2, resulting in downstream effects of NIK stabilization and activation of noncanonical NF-kB signaling, demonstrating cIAP1/2 antagonism. Because of their roles in the evasion of apoptosis, inhibitor of apoptosis proteins (IAP) are considered attractive targets for anticancer therapy. Treatment with this compound leads to TNFa-dependent induction of apoptosis in various cancer cell lines in vitro.
In vivo	Tolinapant (ASTX660) is orally bioavailable in mice and demonstrates prolonged antagonism of XIAP and cIAP1 in vivo. Dosing of this compound in mice bearing breast and melanoma tumor xenografts causes growth inhibition of MDA-MB-231 and A375 xenograft tumors in vivo.
References	[1] https://pubmed.ncbi.nlm.nih.gov/29695633/

Clinical Trial Information

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

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05082259	Recruiting	Advanced Cancer\|Cervical Cancer\|Triple Negative Breast Cancer	Institute of Cancer Research United Kingdom\|Astex Pharmaceuticals Inc.\|Merck Sharp & Dohme LLC\|Cancer Research UK	March 2 2022	Phase 1
NCT04411030	Completed	Healthy Volunteer	Astex Pharmaceuticals Inc.	May 20 2020	Phase 1
NCT02503423	Active not recruiting	Solid Tumors\|Lymphoma	Astex Pharmaceuticals Inc.	July 2015	Phase 1\|Phase 2

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