Downfall of Iniparib: A PARP Inhibitor That Doesn't Inhibit PARP After All
نویسندگان
چکیده
منابع مشابه
Evidence for the efficacy of Iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer.
Pancreatic cancer is an aggressive, frequently fatal malignancy that strikes 37,000 patients annually in the U.S.A. It is poorly responsive to standard chemotherapies such as gemcitabine. Approximately 5-10% of pancreatic cancer occurs in the setting of a BRCA2 mutation. Breast and ovarian carcinomas that harbor BRCA2 mutations are susceptible to the effects of an emerging class of targeted age...
متن کاملIn vitro analysis of PARP inhibitor nanoformulations
PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in a...
متن کاملINVITED COMMENTARY Biomarkers of PARP inhibitor sensitivity
The PARP inhibitors represent one of the most exciting recent developments in cancer therapy. Substantial efficacy has been shown with PARP inhibitors in the treatment of hereditary BRCA1/2 related Breast and Ovarian cancer as single agents [1–3] and in combination with temozolomide [4]. Similarly, encouraging activity has been shown in sporadic ovarian cancer with a PARP inhibitor as a single ...
متن کاملPARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA.
The PARP-3 protein is closely related to the PARP-1 and PARP-2 proteins, which are involved in DNA repair and genome maintenance. Here, we characterized the biochemical properties of human PARP-3. PARP-3 is able to ADP-ribosylate itself as well as histone H1, a previously unknown substrate for PARP-3. PARP-3 is not activated upon binding to DNA and is a mono-ADP-ribosylase, in contrast to PARP-...
متن کاملIniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor.
PURPOSE PARP inhibitors are being developed as therapeutic agents for cancer. More than six compounds have entered clinical trials. The majority of these compounds are β-nicotinamide adenine dinucleotide (NAD(+))-competitive inhibitors. One exception is iniparib, which has been proposed to be a noncompetitive PARP inhibitor. In this study, we compare the biologic activities of two different str...
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ژورنال
عنوان ژورنال: JNCI Journal of the National Cancer Institute
سال: 2014
ISSN: 0027-8874,1460-2105
DOI: 10.1093/jnci/djt447