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
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
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 |
DescriptionSources: http://adisinsight.springer.com/drugs/800028802Curator'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
Sources: http://adisinsight.springer.com/drugs/800028802
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17473206 | https://www.ncbi.nlm.nih.gov/pubmed/24647572
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
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3105 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17473206 |
5.2 nM [Ki] | ||
Target ID: CHEMBL5366 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17473206 |
2.9 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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%) AEs leading toAppetite decreased NOS (grade 3, 8.3%) Fatigue (grade 3, 8.3%) Nausea (grade 3, 8.3%) discontinuation/dose reduction: Fatigue (25%) Sources: Page: p.1836Vomiting (16.7%) Neutropenia (25%) Nausea (25%) Thrombocytopenia (25%) Anemia (8.3%) Essential tremor (8.3%) |
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%) Sources: Page: p.2365Nausea (grade 3, 20%) Vomiting (grade 3, 20%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
Poly (ADP-ribose) polymerase activity regulates apoptosis in HeLa cells after alkylating DNA damage. | 2008 Jun |
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Patient perspectives on phase 0 clinical trials. | 2008 Jun 15 |
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Phase 0 trials: an industry perspective. | 2008 Jun 15 |
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An enzyme-linked immunosorbent poly(ADP-ribose) polymerase biomarker assay for clinical trials of PARP inhibitors. | 2008 Oct 15 |
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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 |
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The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and reduction in PARP activity in vivo. | 2008 Sep-Oct |
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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 |
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ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors. | 2009 Dec 1 |
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94th RSNA Annual Meeting. | 2009 Jan |
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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 |
|
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 |
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Poly(ADP-ribose) polymerase inhibitor induces accelerated senescence in irradiated breast cancer cells and tumors. | 2010 Aug 1 |
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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 |
|
MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. | 2011 Apr 1 |
|
The poly(ADP-Ribose) polymerase inhibitor ABT-888 reduces radiation-induced nuclear EGFR and augments head and neck tumor response to radiotherapy. | 2011 Jun |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26251615
recommended Phase II dose of single-agent veliparib as 400 mg bid.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23054213
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
Edited
Fri Dec 15 17:15:31 GMT 2023
by
admin
on
Fri Dec 15 17:15:31 GMT 2023
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Record UNII |
01O4K0631N
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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EU-Orphan Drug |
EU/3/10/830
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FDA ORPHAN DRUG |
542916
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FDA ORPHAN DRUG |
456514
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NCI_THESAURUS |
C62554
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FDA ORPHAN DRUG |
257108
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FDA ORPHAN DRUG |
246607
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FDA ORPHAN DRUG |
295509
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FDA ORPHAN DRUG |
290209
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11960529
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01O4K0631N
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9211
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CHEMBL506871
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VELIPARIB
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C60768
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912444-00-9
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62880
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DB07232
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100000124275
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DTXSID90238456
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WW-28
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SUB32392
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
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TARGET -> INHIBITOR |
Ki
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METABOLIC ENZYME -> SUBSTRATE |
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TRANSPORTER -> SUBSTRATE |
Veliparib was a weak P-glycoprotein (P-gp) substrate.
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EXCRETED UNCHANGED |
URINE
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EXCRETED UNCHANGED |
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TARGET -> INHIBITOR |
Ki
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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METABOLIC ENZYME -> SUBSTRATE |
Related Record | Type | Details | ||
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METABOLITE LESS ACTIVE -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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