Iniparib (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

, previously known as BSI 201) was a drug candidate for cancer treatment. It was originally believed to act as an

irreversible inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...

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 ...

(hence, a

PARP inhibitor PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on ...

) and possibly other enzymes through

covalent modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosomes ...

, but its effects against PARP were later disproven. It underwent

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

s for treatment of some types of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

, but was discontinued after disappointing phase III clinical trials.

History

Iniparib was the first putative PARP inhibitor to commence

phase III clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

s. The first was for breast cancer, another was for squamous-cell lung cancer. Preliminary results in June 2009 on

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

were promising. Later results showed increased median survival of triple-negative breast cancer patients from 7.7 to 12.2 months. In 2009, the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

began fast-tracking the new drug application of iniparib for triple-negative breast cancer. However, phase III results disclosed in January 2011 were disappointing. Iniparib was also studied as a potential chemotherapeutic agent in the fight against malignant

glioma A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms ...

, including

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

. Glioma is a resilient type of primary brain tumor (not metastatic) that currently has limited effective therapies, especially for patients whose tumors are in an inoperable location of the brain, such as the interior of the brainstem. During the 2013

American Society of Clinical Oncology The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...

conference,

Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

disclosed that iniparib failed to help lung-cancer patients in a late-stage trial, prompting the company to end research into the once-promising compound and take a $285 million charge.

References

{{reflist, 2 Abandoned drugs Benzamides Nitrobenzenes Iodoarenes