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Details

Stereochemistry ACHIRAL
Molecular Formula C24H26N4O
Molecular Weight 386.4894
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Dordaviprone

SMILES

CC1=CC=CC=C1CN2C3=NCCN3C4=C(CN(CC5=CC=CC=C5)CC4)C2=O

InChI

InChIKey=VLULRUCCHYVXOH-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27602582 | https://www.ncbi.nlm.nih.gov/pubmed/25859547 | https://www.ncbi.nlm.nih.gov/pubmed/23390247 | https://www.ncbi.nlm.nih.gov/pubmed/25587031 | https://www.ncbi.nlm.nih.gov/pubmed/24838721

TIC10 (NSC350625 or ONC201) is a small-molecule compound belongs to a chemical class known as imipridones, that possess a unique three-ring heterocycle with two substitutable basic amines. ONC201 has anti-proliferative and pro-apoptotic effects against a broad range of tumor cells but not normal cells. The mechanism of action of ONC201 involves engagement of PERK-independent activation of the integrated stress response, leading to tumor upregulation of DR5 and dual Akt/ERK inactivation, and consequent Foxo3a activation leading to upregulation of the death ligand TRAIL. The isomeric structure of TIC10/ONC201 is critical to its activity: anti-cancer activity is associated with the angular structure and not the linear isomer. Clinical trials are evaluating the single agent efficacy of ONC201 in multiple solid tumors and hematological malignancies and exploring alternative dosing regimens. Oncoceutics is developing ONC 201 as a potential therapy for treatment of p53-deficient cancers (including solid tumours).

Originator

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.6 μg/mL
625 mg 1 times / 3 weeks multiple, oral
dose: 625 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ONC201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
37.7 μg × h/mL
625 mg 1 times / 3 weeks multiple, oral
dose: 625 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ONC201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11.3 h
625 mg 1 times / 3 weeks multiple, oral
dose: 625 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ONC201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
OverviewDrug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.
2013 Feb 6
The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity.
2014 Dec 30
Pharmacophore reassignment for induction of the immunosurveillance cytokine TRAIL.
2014 Jun 23
TIC10/ONC201: a bend in the road to clinical development.
2015
Small-Molecule ONC201/TIC10 Targets Chemotherapy-Resistant Colorectal Cancer Stem-like Cells in an Akt/Foxo3a/TRAIL-Dependent Manner.
2015 Apr 1
Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10.
2015 Apr 15
ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells.
2015 Aug 3
TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo.
2015 Nov 3
The preclinical evaluation of TIC10/ONC201 as an anti-pancreatic cancer agent.
2016 Aug 5
ONC201: Stressing tumors to death.
2016 Feb 16
Discovery and clinical introduction of first-in-class imipridone ONC201.
2016 Nov 8
mTOR inhibition sensitizes ONC201-induced anti-colorectal cancer cell activity.
2016 Sep 30
Patents

Sample Use Guides

The first-in-human clinical trial of ONC201 in advanced aggressive refractory solid tumors confirmed that ONC201 is exceptionally well-tolerated and established the recommended phase II dose of 625 mg administered orally every three weeks defined by drug exposure comparable to efficacious levels in preclinical models.
Route of Administration: Oral
5-10 uM TIC10 induces TRAIL-mediated apoptosis in p53 deficient HCT116 cells.
Name Type Language
Dordaviprone
USAN   INN  
Official Name English
ONC201
Code English
TIC-10
Code English
dordaviprone [INN]
Common Name English
7-benzyl-4-[(2-methylphenyl)methyl]-2,4,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one
Systematic Name English
Imidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one, 2,4,6,7,8,9-hexahydro-4-[(2-methylphenyl)methyl]-7-(phenylmethyl)-
Systematic Name English
TIC10
Code English
2,4,6,7,8,9-Hexahydro-4-[(2-methylphenyl)methyl]-7-(phenylmethyl)imidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one
Systematic Name English
DORDAVIPRONE [USAN]
Common Name English
ONC 201 [WHO-DD]
Common Name English
ONC-201
Code English
NSC-350625
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 553316
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
FDA ORPHAN DRUG 640218
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
Code System Code Type Description
USAN
LM-148
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
CAS
1342897-86-2
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
SUPERSEDED
NCI_THESAURUS
C113792
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
PUBCHEM
73777259
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
FDA UNII
9U35A31JAI
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
INN
12147
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
SMS_ID
300000017123
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
CAS
1616632-77-9
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
DRUG BANK
DB14844
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY
NSC
350625
Created by admin on Sat Dec 16 20:21:40 UTC 2023 , Edited by admin on Sat Dec 16 20:21:40 UTC 2023
PRIMARY