VELIPARIB

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 Search

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

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Poly [ADP-ribose] polymerase-1 23 Target ID: CHEMBL3105 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17473206	Inhibitor 8297		5.2 nM [Ki]
Poly [ADP-ribose] polymerase 2 16 Target ID: CHEMBL5366 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17473206	Inhibitor 8297		2.9 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Glioblastoma 65 Sources: http://adisinsight.springer.com/drugs/800028802	Primary	Phase III 656	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800028802	Primary	Phase III 656	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://adisinsight.springer.com/drugs/800028802	Primary	Phase III 656	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800028802	Primary	Phase III 656	Unknown Approved Use Unknown

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: https://pubmed.ncbi.nlm.nih.gov/29733524 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: https://pubmed.ncbi.nlm.nih.gov/29733524 Page: p.2365	DLT: Seizure... Dose limiting toxicities: Seizure (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/29733524 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: https://pubmed.ncbi.nlm.nih.gov/29733524 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: https://pubmed.ncbi.nlm.nih.gov/29733524 Page: p.2365	Sources: https://pubmed.ncbi.nlm.nih.gov/29733524 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: https://pubmed.ncbi.nlm.nih.gov/28665051 Page: p.1836	unhealthy, ADULT n = 12 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/28665051 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: https://pubmed.ncbi.nlm.nih.gov/28665051 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: https://pubmed.ncbi.nlm.nih.gov/29733524 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: https://pubmed.ncbi.nlm.nih.gov/29733524 Page: p.2365	DLT: Asthenia, Nausea... Dose limiting toxicities: Asthenia (grade 2, 20%) Nausea (grade 3, 20%) Vomiting (grade 3, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/29733524 Page: p.2365

AEs

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY103035	https://www.001chemical.com/chem/search?q=DY103035
1PlusChem LLC	1P003A1L	https://www.1pchem.com/search?query=1P003A1L
1PlusChem LLC	1P006PW0	https://www.1pchem.com/search?query=1P006PW0
A2B Chem	AB52185	http://a2bchem.com/prod/AB52185
A2B Chem	AD12688	http://a2bchem.com/prod/AD12688
AChemBlock	10404	http://www.achemblock.com/catalogsearch/result/?q=10404
AChemBlock	Q70244	http://www.achemblock.com/catalogsearch/result/?q=Q70244
AK Scientific	SYN5722	https://aksci.com/item_detail.php?cat=SYN5722
AK Scientific	X7540	https://aksci.com/item_detail.php?cat=X7540
AK Scientific	Y0314	https://aksci.com/item_detail.php?cat=Y0314
AOBIOUS INC	AOB87114	http://aobious.com/aobious/search?search_query=AOB87114
Angene	AGN-PC-0VRX87	http://www.angenechemical.com/productshow/AGN-PC-0VRX87.html
ApexBio Technology	A3958	https://www.apexbt.com/catalogsearch/result/?q=A3958
AstaTech	41373	http://astatechinc.com/CPSResult.php?CRNO=41373
AstaTech	41382	http://astatechinc.com/CPSResult.php?CRNO=41382
Axon MedChem	1593	https://www.axonmedchem.com/product/1593
Axon MedChem	2888	https://www.axonmedchem.com/product/2888
BLD Pharm	BD160254	http://www.bldpharm.com/search/Search.html?keyword=BD160254
BOC Sciences	912444-00-9	http://www.bocsci.com/description.asp?cas=912444-00-9
Cayman Chemical	11505	http://www.caymanchem.com/app/template/Product.vm/catalog/11505
Chem Scene	CS-0076	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0076
Chem Scene	CS-0077	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0077
ChemShuttle	100936	https://www.chemshuttle.com/catalogsearch/result/?q=100936
ChemShuttle	133768	https://www.chemshuttle.com/catalogsearch/result/?q=133768
Debye Scientific	DB-078941	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-078941
Fluorochem	519795	http://www.fluorochem.co.uk/Products/Product?code=519795
KeyOrganics	AS-17023	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17023
KeyOrganics	AS-19397	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-19397
KeyOrganics	STR12090	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=STR12090
Lab Network	LN01270977	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01270977
Lab Network	LN01325591	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01325591
Matrix Scientific	120689	http://www.matrixscientific.com/120689.html
Matrix Scientific	153553	http://www.matrixscientific.com/153553.html
MedChem Express	HY-10129	https://www.medchemexpress.com/search.html?q=HY-10129&ft=&fa=&fp=
MedChem Express	HY-10130	https://www.medchemexpress.com/search.html?q=HY-10130&ft=&fa=&fp=
MolPort	MolPort-009-679-436	https://www.molport.com/shop/molecule-link/MolPort-009-679-436
MolPort	MolPort-016-631-859	https://www.molport.com/shop/molecule-link/MolPort-016-631-859
MolPort	MolPort-016-633-168	https://www.molport.com/shop/molecule-link/MolPort-016-633-168
MolPort	MolPort-021-804-902	https://www.molport.com/shop/molecule-link/MolPort-021-804-902
MolPort	MolPort-027-720-945	https://www.molport.com/shop/molecule-link/MolPort-027-720-945
Molcore	MC103035	http://www.molcore.com/CatMC103035.html
Molnova	M16548	https://www.molnova.com/en/serch-list.html?keywords=M16548
Molnova	M16549	https://www.molnova.com/en/serch-list.html?keywords=M16549
MuseChem	I005438	https://www.musechem.com/product/I005438.html
MuseChem	I005439	https://www.musechem.com/product/I005439.html
Ryan Scientific	ABT888_HCL	https://ryansci.com/products?q=ABT888_HCL&list_q=&search_type=exact
Ryan Scientific	Histone_Deacetylase_Inhibitor_III	https://ryansci.com/products?q=Histone_Deacetylase_Inhibitor_III&list_q=&search_type=exact
Selleck Chemicals	S1004	http://www.selleckchem.com/search.html?searchDTO.searchParam=S1004
ShangHai Biochempartner	BCP000074	http://www.biochempartner.com/search_BCP000074
ShangHai Biochempartner	BCP01727	http://www.biochempartner.com/search_BCP01727
ShangHai Biochempartner	BCP09427	http://www.biochempartner.com/search_BCP09427
Toronto Research Chemicals	A112580	https://www.trc-canada.com/product-detail/?CatNum=A112580
eMolecules	271447500	https://orderbb.emolecules.com/search/#?query=271447500
eMolecules	295311079	https://orderbb.emolecules.com/search/#?query=295311079
eMolecules	32278019	https://orderbb.emolecules.com/search/#?query=32278019
eMolecules	36788386	https://orderbb.emolecules.com/search/#?query=36788386
eMolecules	43473183	https://orderbb.emolecules.com/search/#?query=43473183
eNovation Chemicals	D210761	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D210761&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1119640162	https://mcule.com/MCULE-1119640162/
mcule	MCULE-3543863580	https://mcule.com/MCULE-3543863580/
mcule	MCULE-3859998796	https://mcule.com/MCULE-3859998796/
mcule	MCULE-6745061181	https://mcule.com/MCULE-6745061181/

PubMed

Title	Date	PubMed
		252160282
Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models.	2007 May 15	17505006
A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia.	2008 Aug	18456354
Poly (ADP-ribose) polymerase activity regulates apoptosis in HeLa cells after alkylating DNA damage.	2008 Jun	18376143
Patient perspectives on phase 0 clinical trials.	2008 Jun 15	18559584
Phase 0 trials: an industry perspective.	2008 Jun 15	18559583
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	18922977
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	18692448
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	19671751
ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors.	2009 Dec 1	19934293
94th RSNA Annual Meeting.	2009 Jan	19115515
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	19143569
Phase 0 trials: a platform for drug development?	2009 Jul 18	19616703
Phase zero launch.	2009 Jun	19513040
Phase 0 trials for anticancer drug development.	2009 Jun	19483703
Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies.	2009 Jun 1	19364967
Phase 0 clinical trials: an answer to drug development stagnation?	2009 Jun 1	19364952
Role of Phase 0 trials in drug development.	2009 Nov	21426052
Immunohistochemical detection of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas.	2009 Nov	19823047
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	19825992
Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms.	2010	20459590
Poly(ADP-ribose) polymerase inhibitor induces accelerated senescence in irradiated breast cancer cells and tumors.	2010 Aug 1	20610628
Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates.	2010 Feb	19526240
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	20005184
Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888.	2010 Feb 16	20092359
PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors.	2010 Jul 1	20530668
Poly(adp-ribose) polymerase inhibitors: a novel drug class with a promising future.	2010 Mar-Apr	20404603
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	20071126
Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.	2010 Oct	20871615
Cetuximab augments cytotoxicity with poly (adp-ribose) polymerase inhibition in head and neck cancer.	2011	21912620
MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers.	2011 Apr 1	21300766
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	21417348
Bortezomib-induced "BRCAness" sensitizes multiple myeloma cells to PARP inhibitors.	2011 Dec 8	21917757
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.	2011 Jul	21633166
Disposition and drug-drug interaction potential of veliparib (ABT-888), a novel and potent inhibitor of poly(ADP-ribose) polymerase.	2011 Jul	21436403
The poly(ADP-Ribose) polymerase inhibitor ABT-888 reduces radiation-induced nuclear EGFR and augments head and neck tumor response to radiotherapy.	2011 Jun	21719137
N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide.	2011 May	21377995
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	21227924
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	22041887
Response of subtype-specific human breast cancer-derived cells to poly(ADP-ribose) polymerase and checkpoint kinase 1 inhibition.	2011 Oct	21707865
Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas.	2011 Sep 1	21795476
Enhanced killing of cancer cells by poly(ADP-ribose) polymerase inhibitors and topoisomerase I inhibitors reflects poisoning of both enzymes.	2012 Feb 3	22158865
Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage.	2014 Sep 16	25136123

Patents

Sample Use Guides

In Vivo Use Guide

recommended Phase II dose of single-agent veliparib as 400 mg bid.

Route of Administration: Oral

In Vitro Use Guide

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.

Name

Type

Language

VELIPARIB

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