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Details

Stereochemistry ABSOLUTE
Molecular Formula C13H16N4O
Molecular Weight 244.2928
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VELIPARIB

SMILES

C[C@@]1(CCCN1)c2nc3cccc(c3[nH]2)C(=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 244.2928
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
A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia.
2008 Aug
Patient perspectives on phase 0 clinical trials.
2008 Jun 15
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
2009 Jan 22
Phase 0 trials: a platform for drug development?
2009 Jul 18
Phase 0 trials for anticancer drug development.
2009 Jun
Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies.
2009 Jun 1
Immunohistochemical detection of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas.
2009 Nov
Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates.
2010 Feb
PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors.
2010 Jul 1
N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide.
2011 May
Enhanced killing of cancer cells by poly(ADP-ribose) polymerase inhibitors and topoisomerase I inhibitors reflects poisoning of both enzymes.
2012 Feb 3
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 Sat Jun 26 10:18:32 UTC 2021
Edited
by admin
on Sat Jun 26 10:18:32 UTC 2021
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
1H-BENZIMIDAZOLE-7-CARBOXAMIDE, 2-((2R)-2-METHYL-2-PYRROLIDINYL)-
Systematic Name English
VELIPARIB [WHO-DD]
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 Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
FDA ORPHAN DRUG 542916
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
NCI_THESAURUS C62554
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
FDA ORPHAN DRUG 295509
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
FDA ORPHAN DRUG 257108
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
FDA ORPHAN DRUG 246607
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
FDA ORPHAN DRUG 456514
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
FDA ORPHAN DRUG 290209
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
Code System Code Type Description
PUBCHEM
11960529
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
FDA UNII
01O4K0631N
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
INN
9211
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
ChEMBL
CHEMBL506871
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
WIKIPEDIA
VELIPARIB
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
NCI_THESAURUS
C60768
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
CAS
912444-00-9
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
DRUG BANK
DB07232
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
EPA CompTox
912444-00-9
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
PRIMARY
EVMPD
SUB32392
Created by admin on Sat Jun 26 10:18:32 UTC 2021 , Edited by admin on Sat Jun 26 10:18:32 UTC 2021
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
TARGET -> INHIBITOR
Ki
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY