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dordaviprone   Click here for help

GtoPdb Ligand ID: 9978

Synonyms: Modeyso® | ONC-201 | ONC201 | TIC-10 | TIC10
Approved drug Immunopharmacology Ligand
dordaviprone is an approved drug
Compound class: Synthetic organic
Comment: Dordaviprone (ONC201, also known as TIC10 [2]) was originally discovered as a TRAIL pathway inducer and as an orally active dual Akt/ERK inhibitor [1]. It exerts potent anti-tumour effects [7,11-12].

ONC201 was later reported as an allosteric activator of the oncology drug target, mitochondrial protease caseinolytic protease P (ClpP) [5-6,10]. It also antagonises dopamine D2/3 receptor signalling [8-9].
2D Structure
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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.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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.

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Hydrogen bond acceptors 3
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 42.53
Molecular weight 386.21
XLogP 5.24
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Cc1ccccc1Cn1c(=O)c2CN(CCc2n2c1=NCC2)Cc1ccccc1
Isomeric SMILES Cc1ccccc1Cn1c(=O)c2CN(CCc2n2c1=NCC2)Cc1ccccc1
InChI InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-23(29)21-17-26(15-19-8-3-2-4-9-19)13-11-22(21)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3
InChI Key VLULRUCCHYVXOH-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
The compound was evaluated in a wide variety of advanced solid tumours (e.g. glioma, neuroendocrine tumours, endometrial cancer, breast cancers, colorectal cancer, non-small cell lung cancer) and in hematological cancers. First approval was granted by the FDA in August 2025, to treat previously-treated, progressing diffuse midline glioma harboring an H3 K27M mutation [4].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05580562 ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) Phase 3 Interventional Chimerix 3
NCT05009992 Combination Therapy for the Treatment of Diffuse Midline Gliomas Phase 2 Interventional University of California, San Francisco
NCT05476939 Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0 Phase 3 Interventional Gustave Roussy, Cancer Campus, Grand Paris