U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C13H16N4O
Molecular Weight 244.2923
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VELIPARIB

SMILES

C[C@@]1(CCCN1)C2=NC3=C(N2)C=CC=C3C(N)=O

InChI

InChIKey=JNAHVYVRKWKWKQ-CYBMUJFWSA-N
InChI=1S/C13H16N4O/c1-13(6-3-7-15-13)12-16-9-5-2-4-8(11(14)18)10(9)17-12/h2,4-5,15H,3,6-7H2,1H3,(H2,14,18)(H,16,17)/t13-/m1/s1

HIDE SMILES / InChI

Molecular Formula C13H16N4O
Molecular Weight 244.2923
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17473206 | https://www.ncbi.nlm.nih.gov/pubmed/26251615

Veliparib (ABT-888) is a potent inhibitor of PARP, has good oral bioavailability, can cross the blood-brain barrier, and potentiates temozolomide, platinums, cyclophosphamide, and radiation in syngeneic and xenograft tumor models. AbbVie is developing veliparib for the treatment of cancers. Clinical trials are underway worldwide, investigating veliparib primarily as part of a combination therapy in oncology indications such as brain, colorectal, melanoma, ovarian, prostate and pancreatic cancers.

CNS Activity

Curator's Comment: Veliparib is brain penetrant in rodents. No human data available but the drug is studying for treatment of brain tumors https://www.ncbi.nlm.nih.gov/pubmed/24908656 | https://www.ncbi.nlm.nih.gov/pubmed/25682091

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.2 nM [Ki]
2.9 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
800 mg 1 times / day multiple, oral
Highest studied dose
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources: Page: p.2365
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.2365
DLT: Seizure...
Dose limiting toxicities:
Seizure (grade 3, 33.3%)
Sources: Page: p.2365
400 mg 2 times / day multiple, oral
MTD
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.2365
unhealthy, ADULT
n = 9
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 9
Sources: Page: p.2365
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
DLT: Vomiting, Appetite decreased NOS...
Disc. AE: Fatigue, Vomiting...
Dose limiting toxicities:
Vomiting (grade 3, 8.3%)
Appetite decreased NOS (grade 3, 8.3%)
Fatigue (grade 3, 8.3%)
Nausea (grade 3, 8.3%)
AEs leading to
discontinuation/dose reduction:
Fatigue (25%)
Vomiting (16.7%)
Neutropenia (25%)
Nausea (25%)
Thrombocytopenia (25%)
Anemia (8.3%)
Essential tremor (8.3%)
Sources: Page: p.1836
600 mg 2 times / day multiple, oral
Studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources: Page: p.2365
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2365
DLT: Asthenia, Nausea...
Dose limiting toxicities:
Asthenia (grade 2, 20%)
Nausea (grade 3, 20%)
Vomiting (grade 3, 20%)
Sources: Page: p.2365
AEs

AEs

AESignificanceDosePopulation
Seizure grade 3, 33.3%
DLT
800 mg 1 times / day multiple, oral
Highest studied dose
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources: Page: p.2365
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.2365
Vomiting 16.7%
Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Fatigue 25%
Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Nausea 25%
Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Neutropenia 25%
Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Thrombocytopenia 25%
Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Anemia 8.3%
Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Essential tremor 8.3%
Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Fatigue grade 3, 8.3%
DLT
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Nausea grade 3, 8.3%
DLT
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Vomiting grade 3, 8.3%
DLT
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Appetite decreased NOS grade 3, 8.3%
DLT, Disc. AE
400 mg 2 times / day multiple, oral
RP2D
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.1836
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.1836
Asthenia grade 2, 20%
DLT
600 mg 2 times / day multiple, oral
Studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources: Page: p.2365
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2365
Nausea grade 3, 20%
DLT
600 mg 2 times / day multiple, oral
Studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources: Page: p.2365
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2365
Vomiting grade 3, 20%
DLT
600 mg 2 times / day multiple, oral
Studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources: Page: p.2365
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2365
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models.
2007 May 1
Phase 0 trials: an industry perspective.
2008 Jun 15
Liquid chromatography-mass spectrometric assay for the quantitation in human plasma of ABT-888, an orally available, small molecule inhibitor of poly(ADP-ribose) polymerase.
2008 Sep 1
Poly(ADP-ribose) polymerase inhibitor ABT-888 potentiates the cytotoxic activity of temozolomide in leukemia cells: influence of mismatch repair status and O6-methylguanine-DNA methyltransferase activity.
2009 Aug
Effective sensitization of temozolomide by ABT-888 is lost with development of temozolomide resistance in glioblastoma xenograft lines.
2009 Feb
94th RSNA Annual Meeting.
2009 Jan
Phase 0 trials: a platform for drug development?
2009 Jul 18
Immunohistochemical detection of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas.
2009 Nov
Patents

Sample Use Guides

recommended Phase II dose of single-agent veliparib as 400 mg bid.
Route of Administration: Oral
Using colon cancer cell lines significant synergy was observed between Veliparib (ABT-888) and irinotecan at concentrations of ABT-888 as low as 0.125 μM. The level of synergy observed correlated with the degree of PARP1 inhibition as measured biochemically in cell lysates. ABT-888 at concentrations of 0.5-4 μM resulted in synergy with oxaliplatin.
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:15:31 GMT 2023
Edited
by admin
on Fri Dec 15 17:15:31 GMT 2023
Record UNII
01O4K0631N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VELIPARIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
PARP-1 INHIBITOR ABT-888
Code English
veliparib [INN]
Common Name English
Veliparib [WHO-DD]
Common Name English
1H-BENZIMIDAZOLE-7-CARBOXAMIDE, 2-((2R)-2-METHYL-2-PYRROLIDINYL)-
Systematic Name English
VELIPARIB [JAN]
Common Name English
ABT-888
Code English
VELIPARIB [USAN]
Common Name English
2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide
Systematic Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/10/830
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
FDA ORPHAN DRUG 542916
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
FDA ORPHAN DRUG 456514
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
NCI_THESAURUS C62554
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
FDA ORPHAN DRUG 257108
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
FDA ORPHAN DRUG 246607
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
FDA ORPHAN DRUG 295509
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
FDA ORPHAN DRUG 290209
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
Code System Code Type Description
PUBCHEM
11960529
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
FDA UNII
01O4K0631N
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
INN
9211
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
ChEMBL
CHEMBL506871
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
WIKIPEDIA
VELIPARIB
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
NCI_THESAURUS
C60768
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
CAS
912444-00-9
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
CHEBI
62880
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
DRUG BANK
DB07232
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
SMS_ID
100000124275
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
EPA CompTox
DTXSID90238456
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
USAN
WW-28
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
EVMPD
SUB32392
Created by admin on Fri Dec 15 17:15:31 GMT 2023 , Edited by admin on Fri Dec 15 17:15:31 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
Veliparib was a weak P-glycoprotein (P-gp) substrate.
EXCRETED UNCHANGED
URINE
EXCRETED UNCHANGED
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY