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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

Molecular Formula C24H26N4O
Molecular Weight 386.4894
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.
2016 Feb 16
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 20:21:39 GMT 2023
Edited
by admin
on Sat Dec 16 20:21:39 GMT 2023
Record UNII
9U35A31JAI
Record Status Validated (UNII)
Record Version
  • Download
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 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
FDA ORPHAN DRUG 640218
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
Code System Code Type Description
USAN
LM-148
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
CAS
1342897-86-2
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
SUPERSEDED
NCI_THESAURUS
C113792
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
PUBCHEM
73777259
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
FDA UNII
9U35A31JAI
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
INN
12147
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
SMS_ID
300000017123
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
CAS
1616632-77-9
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
DRUG BANK
DB14844
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
NSC
350625
Created by admin on Sat Dec 16 20:21:40 GMT 2023 , Edited by admin on Sat Dec 16 20:21:40 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
ANTAGONIST
Related Record Type Details
ACTIVE MOIETY
Experiments showed that TIC10 had potent effects against a variety of tumours, including breast, lymphatic, colon and lung cancer. It was especially effective at triggering cell suicide in glioblastoma, a kind of brain tumour that is notoriously difficult to treat2. Mice with glioblastomas that were treated with TIC10 in combination with bevacizumab a drug used against diseases including brain tumours, and sold under the name Avastin survived three times as long as untreated mice. Even mice treated with TIC-10 alone still had better survival rates (6% longer) than those treated with bevacizumab alone.