Tolinapant (ASTX660)

Catalog No.S8681

For research use only.

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.

Tolinapant (ASTX660) Chemical Structure

CAS No. 1799328-86-1

Selleck's Tolinapant (ASTX660) has been cited by 1 Publication

Purity & Quality Control

Choose Selective IAP Inhibitors

Biological Activity

Description 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.
Targets
cIAP2 [1]
()
cIAP1 [1]
(Cell-free assay)
XIAP [1]
(Cell-free assay)
12 nM 40 nM
In vitro

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 ASTX660 leads to TNFa-dependent induction of apoptosis in various cancer cell lines in vitro.[1]

In vivo

ASTX660 is orally bioavailable in mice and demonstrates prolonged antagonism of XIAP and cIAP1 in vivo. ASTX660 dosing in mice bearing breast and melanoma tumor xenografts causes growth inhibition of MDA-MB-231 and A375 xenograft tumors in vivo.[1]

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: MDA-MB-231, HEK293, A375, SK-MEL-28, WSU-DLCL2
  • Concentrations: 1 nM - 10 μM
  • Incubation Time: 5 min - 4 h
  • Method:

    Live cell imaging. Cells are incubated with ASTX660 in 0.1% (v/v) DMSO, with or without neutralizing anti-TNFa antibody for 5 days, and live images are taken every 3 hours using a 10× objective.

Animal Research:

[1]

  • Animal Models: male BALB/c wild type mice, male SCID mice with MDA-MB-231 xenografts, male nude mice with A375 xenografts
  • Dosages: 5, 10, 20 mg/kg
  • Administration: Oral gavage

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(185.29 mM)
Water Insoluble
Ethanol '100 mg/mL

Chemical Information

Molecular Weight 539.68
Formula

C30H42FN5O3

CAS No. 1799328-86-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1CN(C(CN1)CN2CCOCC2C)CC(=O)N3CC(C4=C3C=C(C(=N4)CO)CC5=CC=C(C=C5)F)(C)C

In vivo Formulation Calculator (Clear solution)

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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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05082259 Not yet recruiting Drug: ASTX660|Drug: Pembrolizumab Advanced Cancer|Cervical Cancer|Triple Negative Breast Cancer Institute of Cancer Research United Kingdom|Astex Pharmaceuticals Inc.|Merck Sharp & Dohme Corp.|Cancer Research UK December 1 2021 Phase 1
NCT04411030 Completed Drug: ASTX660|Drug: Midazolam|Drug: Itraconazole Healthy Volunteer Astex Pharmaceuticals Inc. May 20 2020 Phase 1
NCT02503423 Recruiting Drug: ASTX660 Solid Tumors|Lymphoma Astex Pharmaceuticals Inc. July 2015 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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