Veliparib (ABT-888) is a potential anti-cancer drug acting as a

PARP inhibitor PARP inhibitors are a class of drugs that are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP), which plays a role in repairing DNA in damaged cells. Medical uses of these drugs include the treatment of heri ...

. 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 has been shown to potentiate the effects of many chemotherapeutics, and as such has been part of many combination clinical trials. It inhibits both

PARP1 Poly DP-ribosepolymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly DP-ribosesynthase 1 is an enzyme that in humans is encoded by the ''PARP1'' gene. It is the most abundant of the PARP family of enzymes, accounting for 90% o ...

and PARP2 and thereby induces synthetic lethality. It is still being evaluated for the treatment of

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

Development

Veliparib is being developed by

AbbVie AbbVie Inc. is an American pharmaceutical company headquartered in North Chicago, Illinois. It is ranked sixth on the list of largest biomedical companies by revenue. In 2023, the company's seat in Forbes Global 2000 was 74, and rank 89 on the ...

. It was derived from a prior lead compound (A 620223). The FDA awarded

orphan drug status An orphan drug is a pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by the condition ...

in November 2016 for NSCLC.

Clinical trials

As of 2017, 96 clinical trials involving veliparib had been registered with the FDA. It was included in the I-SPY2

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

trial. Numerous phase I

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s are in progress. Over 40 phase II clinical trials have been registered, for indications such as metastatic melanoma, NSCLC, prostate cancer and brain tumors associated with metastatic primary tumors. Combination trials have evaluated veliparib in combination with

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

temozolomide Temozolomide, sold under the brand name Temodar among others, is an anticancer medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma. Text was copied from this source which is copyright European Medicines Agency ...

topotecan Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the ...

carboplatin Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is a ...

paclitaxel Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...

pemetrexed Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC). It is available as a generic medication. Medical use In February 2004, th ...

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

gemcitabine Gemcitabine, sold under the brand name Gemzar, among others, is a chemotherapy medication used to treat cancers. It is used to treat testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder ca ...

, and others. By June 2014 it was in three phase III trials, for advanced ovarian cancer,

triple-negative breast cancer Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e ...

and in

non-small cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...

(NSCLC). In 2017, AbbVie reported that veliparib failed to improve outcomes in the triple-negative breast cancer and NSCLC trials.

References

{{Chemotherapeutic agents Experimental cancer drugs PARP inhibitors