Iniparib
{{Short description|Chemical compound}}
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{{Drugbox
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| IUPAC_name = 4-Iodo-3-nitrobenzamide
| image = Iniparib.svg
| width = 175
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| legal_status = Development terminated
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| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 160003-66-7
| ATC_prefix = None
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| PubChem = 9796068
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| ChemSpiderID = 7971834
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| UNII = 2ZWI7KHK8F
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D09913
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1170047
| C=7 | H=5 | I=1 | N=2 | O=3
| smiles = c1cc(c(cc1C(=O)N)[N+](=O)[O-])I
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| StdInChI = 1S/C7H5IN2O3/c8-5-2-1-4(7(9)11)3-6(5)10(12)13/h1-3H,(H2,9,11)
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Iniparib (INN,{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 65 | url =https://www.who.int/medicines/publications/druginformation/innlists/RL65.pdf | publisher = World Health Organization | access-date = 20 December 2016 | page = 68 | date = 2011}} previously known as BSI 201) was a drug candidate for cancer treatment. It was originally believed to act as an irreversible inhibitor of PARP1 (hence, a PARP inhibitor) and possibly other enzymes through covalent modification,{{cite journal | vauthors = Patel A, Kaufmann SH | title = Development of PARP inhibitors: an unfinished story | journal = Oncology | location = Williston Park, N.Y. | volume = 24 | issue = 1 | pages = 66, 68 | date = January 2010 | pmid = 20187324 }}{{cite web | title = Iniparib (BSI-201) | url = http://www.biparsciences.com/000011.html | archive-url = https://web.archive.org/web/20100623054505/http://www.biparsciences.com/000011.html | archive-date = 23 June 2010 | work = Our Privacy PolicyBiPar Sciences | publisher = Sanofi-Aventis }} but its effects against PARP were later disproven.{{cite journal | vauthors = Liu X, Shi Y, Maag DX, Palma JP, Patterson MJ, Ellis PA, Surber BW, Ready DB, Soni NB, Ladror US, Xu AJ, Iyer R, Harlan JE, Solomon LR, Donawho CK, Penning TD, Johnson EF, Shoemaker AR | display-authors = 6 | title = Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor | journal = Clinical Cancer Research | volume = 18 | issue = 2 | pages = 510–23 | date = January 2012 | pmid = 22128301 | doi = 10.1158/1078-0432.CCR-11-1973 | doi-access = free }}{{cite journal | vauthors = Patel AG, De Lorenzo SB, Flatten KS, Poirier GG, Kaufmann SH | title = Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro | journal = Clinical Cancer Research | volume = 18 | issue = 6 | pages = 1655–62 | date = March 2012 | pmid = 22291137 | pmc = 3306513 | doi = 10.1158/1078-0432.CCR-11-2890 }} It underwent clinical trials for treatment of some types of breast cancer,{{cite web | title = BSI 201 | url = http://www.parp-inhibitors.com/bsi201.html | archive-url = https://web.archive.org/web/20191209101709/http://www.parp-inhibitors.com/bsi201.html | archive-date = 9 December 2019 | work = Parp Inhibitors }}{{cite news |url=https://www.reuters.com/article/healthNews/idUSTRE54U1FV20090531 |title=New breast cancer drugs block cell repair enzyme | work=Reuters | date=2009-05-31}} but was discontinued after disappointing phase III clinical trials.
History
Iniparib was the first putative PARP inhibitor to commence phase III clinical trials.{{cite book | vauthors = Irshad S, Tutt A | chapter = Clinical Trials Investigating PARP Inhibitors as Single Agents | veditors = Curtin NJ, Sharma RA|title=PARP inhibitors for cancer therapy |date=2015 |publisher=Humana Press |isbn=978-3-319-14151-0 |pages=490 | chapter-url=https://books.google.com/books?id=TbvpCQAAQBAJ&pg=PA490}} The first was for breast cancer,{{ClinicalTrialsGov|NCT00938652|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 }} 2009 to 2012, Primary completion date June 2011 another was for squamous-cell lung cancer.{{ClinicalTrialsGov|NCT01082549|Trial of Gemcitabine/Carboplatin With or Without BSI-201 (a PARP1 Inhibitor) in Patients With Previously Untreated Advanced Squamous Cell Lung Cancer (ECLIPSE) }} 2010 to 2014, PCD 2012 Preliminary results in June 2009 on triple-negative breast cancer were promising.{{cite news |url=http://www.dancewithshadows.com/pillscribe/sanofi%E2%80%99s-new-drug-bsi-201-offers-to-treat-the-toughest-breast-cancer/ |title=Sanofi's new drug BSI 201 offers to treat the toughest breast cancer |date=3 June 2009 |access-date=2009-11-17 |archive-url=https://web.archive.org/web/20091018233201/http://www.dancewithshadows.com/pillscribe/sanofi%E2%80%99s-new-drug-bsi-201-offers-to-treat-the-toughest-breast-cancer/ |archive-date=2009-10-18 |url-status=dead }} Later results showed increased median survival of triple-negative breast cancer patients from 7.7 to 12.2 months.{{cite web |url=http://www.medpagetoday.com/MeetingCoverage/SABCS/17496 |title=SABCS: PARP Inhibitor Data Called 'Spectacular' |date=Dec 2009 }}{{cite news |url=http://www.internalmedicinenews.com/news/oncology-hematology/single-article/parp-inhibitor-adds-nearly-5-months-to-breast-cancer-survival/5b8b2da248.html |title=PARP Inhibitor Adds Nearly 5 Months to Breast Cancer Survival |date=11 Oct 2010 |access-date=12 October 2010 |archive-url=https://web.archive.org/web/20110713045456/http://www.internalmedicinenews.com/news/oncology-hematology/single-article/parp-inhibitor-adds-nearly-5-months-to-breast-cancer-survival/5b8b2da248.html |archive-date=13 July 2011 |url-status=dead |df=dmy-all }}{{cite journal | vauthors = O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C | display-authors = 6 | title = Iniparib plus chemotherapy in metastatic triple-negative breast cancer | journal = The New England Journal of Medicine | volume = 364 | issue = 3 | pages = 205–14 | date = January 2011 | pmid = 21208101 | doi = 10.1056/NEJMoa1011418 | doi-access = free }}
In 2009, the FDA began fast-tracking the new drug application of iniparib for triple-negative breast cancer. However, phase III results disclosed in January 2011 were disappointing.{{cite web |url=http://www.fiercebiotech.com/story/sanofi-breast-cancer-drug-flunks-phase-iii-trial/2011-01-27 |title=Sanofi breast cancer drug flunks Phase III trial | work = Fierce Biotech | date = 28 January 2011 }}{{cite journal | vauthors = O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP | display-authors = 6 | title = Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer | journal = Journal of Clinical Oncology | volume = 32 | issue = 34 | pages = 3840–7 | date = December 2014 | pmid = 25349301 | doi = 10.1200/JCO.2014.55.2984 | doi-access = free }}
Iniparib was also studied as a potential chemotherapeutic agent in the fight against malignant glioma, including glioblastoma. 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 conference, Sanofi 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.{{cite web | vauthors = Torsoli A, Serafino P | date = 3 June 2013 | work = Bloomberg | url = https://www.bloomberg.com/news/2013-06-03/sanofi-ends-iniparib-research-plans-285-million-charge.html | title = Sanofi Ends Iniparib Research}}