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Details

Stereochemistry ACHIRAL
Molecular Formula C24H26N4O.2ClH
Molecular Weight 459.411
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Dordaviprone Hydrochloride

SMILES

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

InChI

InChIKey=HKBXPCQCBQFDML-UHFFFAOYSA-N
InChI=1S/C24H26N4O.2ClH/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;2*1H

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

Molecular Formula ClH
Molecular Weight 36.461
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
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
Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway.
2015 May 1
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 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2α kinases.
2016 Feb 16
ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.
2016 Feb 16
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 14:04:50 GMT 2023
Edited
by admin
on Sat Dec 16 14:04:50 GMT 2023
Record UNII
53VG71J90J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Dordaviprone Hydrochloride
USAN  
Official Name English
ONC201 DIHYDROCHLORIDE
Code 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 hydrogen chloride (1:2)
Systematic Name English
Dordaviprone dihydrochloride
Common Name English
ONC-201 DIHYDROCHLORIDE
Code English
DORDAVIPRONE HYDROCHLORIDE [USAN]
Common 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)-, hydrochloride (1:2)
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 527916
Created by admin on Sat Dec 16 14:04:50 GMT 2023 , Edited by admin on Sat Dec 16 14:04:50 GMT 2023
Code System Code Type Description
FDA UNII
53VG71J90J
Created by admin on Sat Dec 16 14:04:50 GMT 2023 , Edited by admin on Sat Dec 16 14:04:50 GMT 2023
PRIMARY
USAN
LM-149
Created by admin on Sat Dec 16 14:04:50 GMT 2023 , Edited by admin on Sat Dec 16 14:04:50 GMT 2023
PRIMARY
CAS
1638178-82-1
Created by admin on Sat Dec 16 14:04:50 GMT 2023 , Edited by admin on Sat Dec 16 14:04:50 GMT 2023
PRIMARY
PUBCHEM
121596510
Created by admin on Sat Dec 16 14:04:50 GMT 2023 , Edited by admin on Sat Dec 16 14:04:50 GMT 2023
PRIMARY
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