Veliparib

Summary

Veliparib (CHEMBL506871) is a phase-3 clinical-stage small-molecule EC 2.4.2.30 (NAD+ ADP-ribosyltransferase) inhibitor (ATC L01XK05); indicated across 39 conditions including neoplasm and breast carcinoma; with CIViC clinical evidence for 6 variant-indication associations (e.g. BRCA1 Mutation in pancreatic cancer).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: L01XK05
• Indications: 39 conditions
• Clinical trials: 101
• Precision-oncology evidence (CIViC): 6 variant–indication associations
• Chemistry: 244.29 Da · C13H16N4O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL506871
Name	Veliparib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11960529
ChEBI	CHEBI:62880
ATC	L01XK05
Molecular formula	C13H16N4O
Molecular weight	244.29
InChIKey	JNAHVYVRKWKWKQ-CYBMUJFWSA-N

SMILES: C[C@@]1(CCCN1)C2=NC3=C(C=CC=C3N2)C(=O)N

IUPAC name: 2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide

ChEBI definition: A benzimidazole substituted with a carbamoyl group at C-4 and a (2R)-2-methylpyrrolidin-2-yl moiety at C-2. It is a potent, orally bioavailable PARP inhibitor.

Pharmacological roles (ChEBI): EC 2.4.2.30 (NAD+ ADP-ribosyltransferase) inhibitor.

Also known as: ABT-888, PARP-1 INHIBITOR ABT-888, Veliparib, VELIPARIB, ABT888, UNII-01O4K0631N, ABT 888, ABT-888 (VELIPARIB), VELIPARIB (ABT-888), NSC 737664, ABT-888 (Veliparib)

Parent form; salt/anhydrous children: CHEMBL5723363

Patent coverage: 2,192 distinct patent families (5,421 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 5,048 (93%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Protein mono-ADP-ribosyltransferase PARP14, Protein mono-ADP-ribosyltransferase PARP10, Protein mono-ADP-ribosyltransferase PARP12, Poly [ADP-ribose] polymerase 1, PARP 1, 2 and 3, Protein mono-ADP-ribosyltransferase PARP3, Poly [ADP-ribose] polymerase 2, Protein mono-ADP-ribosyltransferase PARP4, Poly [ADP-ribose] polymerase tankyrase-2, Poly [ADP-ribose] polymerase tankyrase-1.

Bioactivity

ChEMBL activities: 68 potent at pChembl ≥ 5 of 78 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PARP1	10.21	IC50	0.06	nM	CHEMBL_ACT_25616298
PARP1	9	IC50	1	nM	CHEMBL_ACT_19442024
PARP1	8.96	IC50	1.1	nM	CHEMBL_ACT_19447178
PARP2	8.89	IC50	1.3	nM	CHEMBL_ACT_19447199
PARP1	8.84	IC50	1.45	nM	CHEMBL_ACT_25997325
PARP1	8.83	IC50	1.48	nM	CHEMBL_ACT_18847666
PARP1	8.82	IC50	1.5	nM	CHEMBL_ACT_18847665
PARP1	8.77	Kd	1.7	nM	CHEMBL_ACT_15685814
PARP1	8.7	EC50	2	nM	CHEMBL_ACT_2251365
PARP1	8.7	EC50	2	nM	CHEMBL_ACT_2943608
PARP2	8.54	IC50	2.9	nM	CHEMBL_ACT_18847947
PARP1	8.54	Kd	2.9	nM	CHEMBL_ACT_24867467
PARP2	8.54	Ki	2.9	nM	CHEMBL_ACT_24984333
PARP2	8.54	Ki	2.9	nM	CHEMBL_ACT_29118525
PARP2	8.54	IC50	2.9	nM	CHEMBL_ACT_29252851
PARP1	8.48	IC50	3.31	nM	CHEMBL_ACT_17967326
PARP1	8.48	IC50	3.3	nM	CHEMBL_ACT_17967465
PARP1	8.48	Ki	3.3	nM	CHEMBL_ACT_24775563
PARP1	8.48	IC50	3.3	nM	CHEMBL_ACT_25097966
PARP1	8.32	IC50	4.73	nM	CHEMBL_ACT_16475224
PARP1	8.32	IC50	4.73	nM	CHEMBL_ACT_25950809
PARP1	8.3	IC50	5	nM	CHEMBL_ACT_15650853
PARP1	8.3	IC50	5	nM	CHEMBL_ACT_18847946
PARP1	8.3	Ki	5	nM	CHEMBL_ACT_2251323
PARP2	8.3	Ki	5	nM	CHEMBL_ACT_2251358
PARP1	8.3	Ki	5	nM	CHEMBL_ACT_2943606
PARP1	8.29	IC50	5.18	nM	CHEMBL_ACT_18134877
PARP1	8.28	IC50	5.2	nM	CHEMBL_ACT_13882673
PARP1	8.28	Ki	5.2	nM	CHEMBL_ACT_24984331
PARP1	8.28	Ki	5.2	nM	CHEMBL_ACT_25097965

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

39 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
neoplasm	3	MONDO:0005070	EFO:0000616
breast carcinoma	3	MONDO:0004989	EFO:0000305
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
ovarian carcinoma	3	MONDO:0005140	EFO:0001075
breast neoplasm	3	MONDO:0021100	MONDO:0007254
ovarian cancer	3	MONDO:0008170	MONDO:0008170
ovarian neoplasm	3	MONDO:0021068	EFO:0003893
hereditary breast ovarian cancer syndrome	2	MONDO:0003582	Orphanet:145
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
small cell lung carcinoma	2	MONDO:0008433	EFO:0000702
prostate carcinoma	2	MONDO:0005159	EFO:0001663
metastatic melanoma	2	MONDO:0005191	EFO:0002617
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
testicular cancer	2	MONDO:0005447	EFO:0005088
triple-negative breast carcinoma	2	MONDO:0005494	EFO:0005537
gliosarcoma	2	MONDO:0016681	EFO:1001465
anaplastic astrocytoma	2	MONDO:0016684	EFO:0002499
angiosarcoma	2	MONDO:0016982	EFO:0003968
fallopian tube neoplasm	2	MONDO:0021092	MONDO:0002158
skin neoplasm	2	MONDO:0002531	MONDO:0002898
melanoma	2	MONDO:0005105	EFO:0000756
colorectal neoplasm	2	MONDO:0005335	MONDO:0005575
glioma	2	MONDO:0021042	MONDO:0100342
lymphoma	1	MONDO:0005062	EFO:0000574
squamous cell lung carcinoma	1	MONDO:0005097	EFO:0000708
non-Hodgkin lymphoma	1	MONDO:0018908	EFO:0005952
male breast carcinoma	1	MONDO:0005628	EFO:0006861
rectal cancer	1	MONDO:0006519	EFO:1000657
mantle cell lymphoma	1	MONDO:0018876	EFO:1001469
undifferentiated carcinoma	1	MONDO:0005617	EFO:0006772
central nervous system neoplasm	1	MONDO:0006130	EFO:1000158
gastric neoplasm	1	MONDO:0021085	MONDO:0001056
T-cell non-Hodgkin lymphoma	1	MONDO:0015760	MONDO:0015760
lung adenocarcinoma	1	MONDO:0005061	EFO:0000571
lung large cell carcinoma	1	MONDO:0003050	EFO:0003050
cystic, mucinous, and serous neoplasm	1	MONDO:0006720	MONDO:0037256

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 101.

Phase distribution

Phase	Trials
PHASE1	53
PHASE2	28
PHASE1/PHASE2	11
PHASE3	5
Not specified	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02152982	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
NCT02032277	PHASE3	COMPLETED	A Study Evaluating Safety and Efficacy of the Addition of ABT-888 Plus Carboplatin Versus the Addition of Carboplatin to Standard Chemotherapy Versus Standard Chemotherapy in Subjects With Early Stage Triple Negative Breast Cancer
NCT02106546	PHASE3	COMPLETED	Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Advanced or Metastatic Squamous Non-Small Cell Lung Cancer
NCT02163694	PHASE3	COMPLETED	A Phase 3 Randomized, Placebo-controlled Trial of Carboplatin and Paclitaxel With or Without Veliparib (ABT-888) in HER2-negative Metastatic or Locally Advanced Unresectable BRCA-associated Breast Cancer
NCT02264990	PHASE3	COMPLETED	Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator’s Choice of Standard Chemotherapy in Adults Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers
NCT02470585	PHASE3	TERMINATED	Veliparib With Carboplatin and Paclitaxel and as Continuation Maintenance Therapy in Adults With Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT01012817	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Veliparib and Topotecan Hydrochloride in Treating Patients With Solid Tumors, Relapsed or Refractory Ovarian Cancer, or Primary Peritoneal Cancer
NCT01042379	PHASE2	RECRUITING	I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
NCT01386385	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT01585805	PHASE2	ACTIVE_NOT_RECRUITING	Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT01638546	PHASE2	ACTIVE_NOT_RECRUITING	Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer
NCT03289910	PHASE2	ACTIVE_NOT_RECRUITING	Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia
NCT03581292	PHASE2	ACTIVE_NOT_RECRUITING	Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations
NCT00804908	PHASE2	COMPLETED	A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma
NCT01009788	PHASE2	COMPLETED	ABT-888 and Temozolomide for Metastatic Breast Cancer and BRCA1/2 Breast Cancer
NCT01051596	PHASE2	COMPLETED	A Study of ABT-888 in Combination With Temozolomide for Colorectal Cancer
NCT01113957	PHASE2	COMPLETED	A Trial of ABT-888 in Combination With Temozolomide Versus Pegylated Liposomal Doxorubicin Alone in Ovarian Cancer
NCT01149083	PHASE2	COMPLETED	Veliparib With or Without Carboplatin in Treating Patients With Stage III or IV Breast Cancer
NCT01193140	PHASE2	COMPLETED	To Evaluate the Safety of Veliparib in Combination With Temozolomide in Subjects With Solid Tumors
NCT01205828	PHASE2	TERMINATED	ABT-888 and Temozolomide for Liver Cancer
NCT01266447	PHASE2	COMPLETED	Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer
NCT01306032	PHASE2	COMPLETED	Phase II ABT-888 With Cyclophosphamide
NCT01326702	PHASE1/PHASE2	COMPLETED	Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors
NCT01472783	PHASE1/PHASE2	COMPLETED	Veliparib Monotherapy for Relapsed Ovarian Cancer With BRCA Mutation
NCT01489865	PHASE1/PHASE2	COMPLETED	ABT-888 With Modified FOLFOX6 in Patients With Metastatic Pancreatic Cancer
NCT01506609	PHASE2	COMPLETED	Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide (TMZ) or In Combination With Carboplatin and Paclitaxel Versus Placebo in Participants With Breast Cancer Gene (BRCA)1 and BRCA2 Mutation and Metastatic Breast Cancer
NCT01514201	PHASE1/PHASE2	COMPLETED	Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas
NCT01540565	PHASE2	COMPLETED	Veliparib in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT01560104	PHASE2	COMPLETED	A Clinical Study Conducted in Multiple Centers Comparing Veliparib in Combination With Carboplatin and Paclitaxel Versus a Placebo in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non-small Cell Lung Cancer
NCT01576172	PHASE2	COMPLETED	Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
NCT01642251	PHASE1/PHASE2	COMPLETED	Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer
NCT01657799	PHASE2	COMPLETED	Comparison of Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Adults With Brain Metastases From Non-Small Cell Lung Cancer
NCT01690598	PHASE1/PHASE2	COMPLETED	Veliparib and Topotecan for Relapsed Ovarian Cancer With Negative or Unknown BRCA Status
NCT01711541	PHASE1/PHASE2	COMPLETED	Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer
NCT01818063	PHASE2	COMPLETED	Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer
NCT01827384	PHASE2	COMPLETED	MPACT Study to Compare Effects of Targeted Drugs on Tumor Gene Variations
NCT02289690	PHASE1/PHASE2	COMPLETED	Dose Escalation and Double-blind Study of Veliparib in Combination With Carboplatin and Etoposide in Treatment-naive Extensive Stage Disease Small Cell Lung Cancer
NCT02305758	PHASE2	COMPLETED	Study Comparing Veliparib Plus FOLFIRI Versus Placebo Plus FOLFIRI With or Without Bevacizumab in Previously Untreated Metastatic Colorectal Cancer
NCT02412371	PHASE1/PHASE2	TERMINATED	A Study Evaluating the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Adults With Stage III Non-Small Cell Lung Cancer (NSCLC)
NCT02595905	PHASE2	COMPLETED	Cisplatin With or Without Veliparib in Treating Patients With Recurrent or Metastatic Triple-Negative and/or BRCA Mutation-Associated Breast Cancer With or Without Brain Metastases

Clinical evidence (CIViC)

Variant × indication × effect (6 predictive associations from 6 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
BRCA1 Mutation	Pancreatic Cancer	Sensitivity/Response	Cisplatin + Gemcitabine + Veliparib	CIViC B	EID5932
BRCA1 Mutation	Pancreatic Cancer	Sensitivity/Response	Veliparib	CIViC B	EID5934
BRCA2 Mutation	Pancreatic Cancer	Sensitivity/Response	Cisplatin + Gemcitabine + Veliparib	CIViC B	EID5933
BRCA2 Mutation	Pancreatic Cancer	Sensitivity/Response	Veliparib	CIViC B	EID5935
CDK12 Loss-of-function	Prostate Cancer	Sensitivity/Response	Talazoparib + Olaparib + Rucaparib + Veliparib	CIViC D	EID12572
MYCN Overexpression	Neuroblastoma	Sensitivity/Response	Niraparib + Veliparib + Olaparib + Talazoparib	CIViC D	EID9006

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).