Veliparib

Veliparib

Systematic (IUPAC) name
2-((R)-2-Methylpyrrolidin-2-yl)-1H-benzimidazole-4-carboxamide
Legal status
Legal status	experimental
Identifiers
ATC code	none
PubChem	CID 11960529
IUPHAR/BPS	7417
DrugBank	DB07232
ChemSpider	10134775
UNII	01O4K0631N
ChEMBL	CHEMBL506871
Chemical data
Formula	C13H16N4O
Molar mass	244.29 g/mol
SMILES NC(=O)c1cccc(n2)c1nc2C3(C)NCCC3
InChI 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 Key:JNAHVYVRKWKWKQ-CYBMUJFWSA-N
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Veliparib (ABT-888)^[1] is a potential anti-cancer drug acting as a PARP inhibitor. It kills cancer cells by blocking a protein called PARP, thereby preventing the repair of DNA or genetic damage in cancer cells and possibly making them more susceptible to anticancer treatments. Veliparib may make whole brain radiation treatment work more effectively against brain metastases from NSCLC.

It inhibits both PARP1 and PARP2.^[2][3]

Clinical trials

Numerous phase I clinical trials are in progress.^[4]

A phase I/II clinical trial for use with/out doxorubicin (for Metastatic or Unresectable Solid Tumors or Non-Hodgkin Lymphoma) started in 2008 and is due to complete in 2010.^[5] Results (inc MTD) with topotecan.^[6]

A phase II clinical trial for metastatic melanoma has started recruiting.^[7] Due to end Dec 2011.

A phase II clinical trial for metastatic breast cancer has started recruiting.^[8] Due to end Nov 2011.

A phase II clinical trial for add-on to Radiation Therapy for Patients with Brain Metastases from Non-Small Cell Lung Cancer.

It was included in the I-SPY2 breast cancer trial,^[9] and there are encouraging data from that study ^[10]

A phase I clinical trial for prostate cancer in men who carry the BRCA mutation is underway and is now recruiting (as of May 2013).^[11]

By June 2014 it was in three phase III trials, for advanced ovarian cancer, triple-negative breast cancer and in non-small cell lung cancer (NSCLC).^[12]

References

1. "ABT-888, an Orally Active Poly(ADP-Ribose) Polymerase Inhibitor that Potentiates DNA-Damaging Agents in Preclinical Tumor Models" May 2007
2. http://www.cancer.gov/drugdictionary/?CdrID=496464
3. "ABT-888, an Orally Active Poly(ADP-Ribose) Polymerase Inhibitor that Potentiates DNA-Damaging Agents in Preclinical Tumor Models", 2007
4. http://clinicaltrialsfeeds.org/clinical-trials/results/term=Drug:+ABT-888
5. "ABT-888 and Cyclophosphamide With Versus Without Doxorubicin in Treating Patients With Metastatic or Unresectable Solid Tumors or Non-Hodgkin Lymphoma"
6. "Phase I Study of ABT-888, a PARP Inhibitor, in Combination with Topotecan Hydrochloride in Adults with Refractory Solid Tumors and Lymphomas.". July 2011. doi:10.1158/0008-5472.CAN-11-1227.
7. "A Study Evaluating Efficacy of ABT-888 in Combination With Temozolomide in Metastatic Melanoma"
8. "ABT-888 and Temozolomide for Metastatic Breast Cancer"
9. "Breast cancer study aims to speed drugs, cooperation", March 2010
10. http://www.centerwatch.com/news-online/article/5737/new-presurgery-combination-therapy-for-triple-negative-breast-cancer
11. "Veliparib in Treating Patients With Malignant Solid Tumors That Did Not Respond to Previous Therapy. Clinical Trial NCT00892736"
12. AbbVie takes PARP inhibitor into third phase III trial. June 2014

External links

http://kdwn.com/2013/12/16/new-drug-study-method-show-breast-cancer-promise/