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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
Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models.
2007 May 15
A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia.
2008 Aug
Poly (ADP-ribose) polymerase activity regulates apoptosis in HeLa cells after alkylating DNA damage.
2008 Jun
Patient perspectives on phase 0 clinical trials.
2008 Jun 15
Phase 0 trials: an industry perspective.
2008 Jun 15
Preclinical modeling of a phase 0 clinical trial: qualification of a pharmacodynamic assay of poly (ADP-ribose) polymerase in tumor biopsies of mouse xenografts.
2008 Nov 1
Potentiation of temozolomide cytotoxicity by poly(ADP)ribose polymerase inhibitor ABT-888 requires a conversion of single-stranded DNA damages to double-stranded DNA breaks.
2008 Oct
An enzyme-linked immunosorbent poly(ADP-ribose) polymerase biomarker assay for clinical trials of PARP inhibitors.
2008 Oct 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
The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and reduction in PARP activity in vivo.
2008 Sep-Oct
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
ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors.
2009 Dec 1
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
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 zero launch.
2009 Jun
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
Phase 0 clinical trials: an answer to drug development stagnation?
2009 Jun 1
Role of Phase 0 trials in drug development.
2009 Nov
Immunohistochemical detection of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas.
2009 Nov
Acquired resistance to combination treatment with temozolomide and ABT-888 is mediated by both base excision repair and homologous recombination DNA repair pathways.
2009 Oct
Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms.
2010
Poly(ADP-ribose) polymerase inhibitor induces accelerated senescence in irradiated breast cancer cells and tumors.
2010 Aug 1
Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates.
2010 Feb
Simultaneous determination of ABT-888, a poly (ADP-ribose) polymerase inhibitor, and its metabolite in human plasma by liquid chromatography/tandem mass spectrometry.
2010 Feb 1
Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888.
2010 Feb 16
PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors.
2010 Jul 1
Poly(adp-ribose) polymerase inhibitors: a novel drug class with a promising future.
2010 Mar-Apr
A rapid and sensitive method for determination of veliparib (ABT-888), in human plasma, bone marrow cells and supernatant by using LC/MS/MS.
2010 May 1
Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.
2010 Oct
Cetuximab augments cytotoxicity with poly (adp-ribose) polymerase inhibition in head and neck cancer.
2011
MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers.
2011 Apr 1
5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2).
2011 Apr 14
Bortezomib-induced "BRCAness" sensitizes multiple myeloma cells to PARP inhibitors.
2011 Dec 8
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
2011 Jul
Disposition and drug-drug interaction potential of veliparib (ABT-888), a novel and potent inhibitor of poly(ADP-ribose) polymerase.
2011 Jul
The poly(ADP-Ribose) polymerase inhibitor ABT-888 reduces radiation-induced nuclear EGFR and augments head and neck tumor response to radiotherapy.
2011 Jun
N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide.
2011 May
Poly(ADP-ribose) polymerase and XPF-ERCC1 participate in distinct pathways for the repair of topoisomerase I-induced DNA damage in mammalian cells.
2011 May
Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells.
2011 Nov 15
Response of subtype-specific human breast cancer-derived cells to poly(ADP-ribose) polymerase and checkpoint kinase 1 inhibition.
2011 Oct
Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas.
2011 Sep 1
Enhanced killing of cancer cells by poly(ADP-ribose) polymerase inhibitors and topoisomerase I inhibitors reflects poisoning of both enzymes.
2012 Feb 3
Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage.
2014 Sep 16
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