Iniparib
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| ECHA InfoCard | 100.210.980 |
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| Formula | C7H5IN2O3 |
| Molar mass | 292.032g·mol−1 |
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Iniparib(INN,[1]previously known asBSI 201) was a drug candidate for cancer treatment. It was originally believed to act as anirreversible inhibitorofPARP1(hence, aPARP inhibitor) and possibly other enzymes throughcovalent modification,[2][3]but its effects against PARP were later disproven.[4][5]It underwentclinical trialsfor treatment of some types ofbreast cancer,[6][7]but was discontinued after disappointing phase III clinical trials.
History
[edit]Iniparib was the first putative PARP inhibitor to commencephase III clinical trials.[8]The first was for breast cancer,[9]another was forsquamous-cell lung cancer.[10]Preliminary results in June 2009 ontriple-negative breast cancerwere promising.[11]Later results showed increased median survival of triple-negative breast cancer patients from 7.7 to 12.2 months.[12][13][14]
In 2009, theFDAbeganfast-trackingthenew drug applicationof iniparib for triple-negative breast cancer. However, phase III results disclosed in January 2011 were disappointing.[15][16]
Iniparib was also studied as a potential chemotherapeutic agent in the fight against malignantglioma,includingglioblastoma.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 2013American Society of Clinical Oncologyconference,Sanofidisclosed 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.[15][17]
References
[edit]- ^"International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 65"(PDF).World Health Organization. 2011. p. 68.Retrieved20 December2016.
- ^Patel A, Kaufmann SH (January 2010). "Development of PARP inhibitors: an unfinished story".Oncology.24(1). Williston Park, N.Y.: 66, 68.PMID20187324.
- ^"Iniparib (BSI-201)".Our Privacy PolicyBiPar Sciences.Sanofi-Aventis. Archived fromthe originalon 23 June 2010.
- ^Liu X, Shi Y, Maag DX, Palma JP, Patterson MJ, Ellis PA, et al. (January 2012)."Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor".Clinical Cancer Research.18(2): 510–23.doi:10.1158/1078-0432.CCR-11-1973.PMID22128301.
- ^Patel AG, De Lorenzo SB, Flatten KS, Poirier GG, Kaufmann SH (March 2012)."Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro".Clinical Cancer Research.18(6): 1655–62.doi:10.1158/1078-0432.CCR-11-2890.PMC3306513.PMID22291137.
- ^"BSI 201".Parp Inhibitors.Archived fromthe originalon 9 December 2019.
- ^"New breast cancer drugs block cell repair enzyme".Reuters.2009-05-31.
- ^Irshad S, Tutt A (2015)."Clinical Trials Investigating PARP Inhibitors as Single Agents".In Curtin NJ, Sharma RA (eds.).PARP inhibitors for cancer therapy.Humana Press. p. 490.ISBN978-3-319-14151-0.
- ^Clinical trial numberNCT00938652for "A Phase 3, Multi-Center Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer" atClinicalTrials.gov2009 to 2012, Primary completion date June 2011
- ^Clinical trial numberNCT01082549for "Trial of Gemcitabine/Carboplatin With or Without BSI-201 (a PARP1 Inhibitor) in Patients With Previously Untreated Advanced Squamous Cell Lung Cancer (ECLIPSE)" atClinicalTrials.gov2010 to 2014, PCD 2012
- ^"Sanofi's new drug BSI 201 offers to treat the toughest breast cancer".3 June 2009. Archived fromthe originalon 2009-10-18.Retrieved2009-11-17.
- ^"SABCS: PARP Inhibitor Data Called 'Spectacular'".Dec 2009.
- ^"PARP Inhibitor Adds Nearly 5 Months to Breast Cancer Survival".11 October 2010. Archived fromthe originalon 13 July 2011.Retrieved12 October2010.
- ^O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, et al. (January 2011)."Iniparib plus chemotherapy in metastatic triple-negative breast cancer".The New England Journal of Medicine.364(3): 205–14.doi:10.1056/NEJMoa1011418.PMID21208101.
- ^ab"Sanofi breast cancer drug flunks Phase III trial".Fierce Biotech.28 January 2011.
- ^O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, et al. (December 2014)."Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer".Journal of Clinical Oncology.32(34): 3840–7.doi:10.1200/JCO.2014.55.2984.PMID25349301.
- ^Torsoli A, Serafino P (3 June 2013)."Sanofi Ends Iniparib Research".Bloomberg.