ONC201   Click here for help

GtoPdb Ligand ID: 9978

Synonyms: ONC-201 | TIC-10 | TIC10
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: ONC201 (also known as TIC10 [2]) was originally discovered as a TRAIL receptor inducer and as an orally active dual Akt/ERK inhibitor [1] It exerts potent anti-tumour effects.
Note that although [1] and [2] are published by the same research group, both articles show different isomers of the chemical structure. We show the structure from their 2016 paper, which introduces ONC201 as the first-in-class imipridone anti-cancer compound [1]. PubChem CID 336423 represents the alternative isomer as depicted in the 2013 paper [2].

ONC201 was later reported as an allosteric activator of the mitochondrial protease caseinolytic protease P (ClpP) [4]. ClpP is an oncology drug target [3].
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 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
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 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
References
1. Allen JE, Kline CL, Prabhu VV, Wagner J, Ishizawa J, Madhukar N, Lev A, Baumeister M, Zhou L, Lulla A et al.. (2016)
Discovery and clinical introduction of first-in-class imipridone ONC201.
Oncotarget, 7 (45): 74380-74392. [PMID:27602582]
2. Allen JE, Krigsfeld G, Mayes PA, Patel L, Dicker DT, Patel AS, Dolloff NG, Messaris E, Scata KA, Wang W et al.. (2013)
Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.
Sci Transl Med, 5 (171): 171ra17. [PMID:23390247]
3. Ishizawa J, Zarabi SF, Davis RE, Halgas O, Nii T, Jitkova Y, Zhao R, St-Germain J, Heese LE, Egan G et al.. (2019)
Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality.
Cancer Cell, 35 (5): 721-737.e9. [PMID:31056398]
4. Prabhu VV, Morrow S, Rahman Kawakibi A, Zhou L, Ralff M, Ray J, Jhaveri A, Ferrarini I, Lee Y, Parker C et al.. (2020)
ONC201 and imipridones: Anti-cancer compounds with clinical efficacy.
Neoplasia, 22 (12): 725-744. [PMID:33142238]
5. Wagner J, Kline CL, Zhou L, Campbell KS, MacFarlane AW, Olszanski AJ, Cai KQ, Hensley HH, Ross EA, Ralff MD et al.. (2018)
Dose intensification of TRAIL-inducing ONC201 inhibits metastasis and promotes intratumoral NK cell recruitment.
J Clin Invest, 128 (6): 2325-2338. [PMID:29533922]