tolinapant   Click here for help

GtoPdb Ligand ID: 12704

Synonyms: ASTX-660 | ASTX660 | compound 27 [PMID: 30091600]
Compound class: Synthetic organic
Comment: Tolinapant (ASTX660) is a non-peptidomimetic inhibitor of cIAP1/2 and XIAP, that was discovered using fragment-based drug design [1,4]. It is a Smac mimetic that induces TNFα-mediated necroptosis (inflammatory cell death) in cancer cells [3]. ASTX660 was designed for anticancer potential, and is active in in vitro and in vivo cancer models.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 80.64
Molecular weight 539.69
XLogP -0.39
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES C[C@@H]1CN(CC(=O)N2CC(C)(C)C3=NC(=C(CC4=CC=C(C=C4)F)C=C32)CO)[C@H](CN1)CN5CCOC[C@H]5C
Isomeric SMILES O=C(N1C=2C=C(CC3=CC=C(F)C=C3)C(CO)=NC2C(C1)(C)C)CN4C[C@H](NC[C@@H]4CN5[C@@H](COCC5)C)C
InChI InChI=1S/C30H42FN5O3/c1-20-14-35(25(13-32-20)15-34-9-10-39-18-21(34)2)16-28(38)36-19-30(3,4)29-27(36)12-23(26(17-37)33-29)11-22-5-7-24(31)8-6-22/h5-8,12,20-21,25,32,37H,9-11,13-19H2,1-4H3/t20-,21-,25-/m1/s1
InChI Key YCXOHEXZVKOGEV-DNRQZRRGSA-N
No information available.
Summary of Clinical Use Click here for help
ASTX660 was progreassed to clinical evaluations to evaluate efficacy against various solid and liquid tumours.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05245682 Tolinapant and Radiation for Cisplatin-Ineligible, Previously Untreated, Locally Advanced Head and Neck Cancer Early Phase 1 Interventional Emory University
NCT05403450 A Study of Tolinapant in Combination With Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma (R/R PTCL) Phase 1/Phase 2 Interventional Astex Pharmaceuticals, Inc.
NCT02503423 Phase 1-2 Study of ASTX660 in Subjects With Advanced Solid Tumors and Lymphomas Phase 1/Phase 2 Interventional Astex Pharmaceuticals, Inc. 2