Home Metabolism IAP antagonist Tolinapant (ASTX660) For research use only.

Tolinapant (ASTX660)

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

Tolinapant (ASTX660) Chemical Structure

CAS No. 1799328-86-1

Purity & Quality Control

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

Tolinapant (ASTX660) Related Products

Signaling Pathway

IAP Signaling Pathways

IAP Signaling Pathway

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
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]
Cell Research 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.
In Vivo
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]
Animal Research 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
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

Chemical Information & Solubility

Molecular Weight 539.68 Formula

C30H42FN5O3
CAS No. 1799328-86-1 SDF --
Smiles CC1CN(C(CN1)CN2CCOCC2C)CC(=O)N3CC(C4=C3C=C(C(=N4)CO)CC5=CC=C(C=C5)F)(C)C
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (185.29 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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In vivo
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In vivo Formulation Calculator

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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.

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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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