Delving into the Latest Updates on Iniparib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

4-iodo-3-nitrobenzamide, Iniparib (USAN/INN), NIBA

+ [5]

Target

PARP1

Mechanism

PARP1 inhibitors(Poly (ADP-Ribose) polymerase 1 inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesNervous System Diseases+ [4]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmBrain metastasesEstrogen receptor-negative breast cancer+ [13]

Originator Organization

Sanofi

Active Organization-

Inactive Organization

Sanofi

Drug Highest PhasePendingPhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC7H5IN2O3

InChIKeyMDOJTZQKHMAPBK-UHFFFAOYSA-N

CAS Registry160003-66-7

Primary Objective:
To assess the safety and the maximum tolerated dose(MTD) of iniparib as a single agent and in combination with chemotherapeutic regimens in patients with advanced solid tumors that are refractory to standard therapy.
Secondary Objectives:
To assess the antitumor effect of iniparib (per Response Evaluation Criteria in Solid Tumors [RECIST]) Version 1.1 in patients with measurable disease.
To characterize iniparib (and its metabolites, if possible) pharmacokinetics.
Based on data generated by Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

Start Date01 Nov 2011

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Iniparib

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100 Translational Medicine associated with Iniparib

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100 Patents (Medical) associated with Iniparib

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105

Literatures (Medical) associated with Iniparib

25 Jul 2023·Langmuir : the ACS journal of surfaces and colloids

Affinity Chromatographic Method for Determining Drug-Protein Interaction with Enhanced Speed Than Typical Frontal Analysis.

Article

Author: Zhang, Yajun ; Zhao, Xinfeng ; Qiao, Sai ; Li, Ting ; Zhao, Xue ; Ou, Yuanyuan ; Qu, Lejing ; Zheng, Xinxin

Revealing drug-protein interaction is highly important to select a drug candidate with improved drug-like properties in the early stages of drug discovery. This highlights the urgent need to develop assays that enable the analysis of drug-protein interaction with high speed. Herein, this purpose was realized by the development of an affinity chromatographic method with a two-fold higher speed than typical assays like frontal analysis and zonal elution. The method involved synthesis of a stationary phase by immobilizing poly(ADP-ribose) polymerase-1 (PARP₁) onto macroporous silica gel through a one-step bioorthogonal reaction, characterization of mutual displacement interaction of two canonical drugs to the immobilized PARP₁, determination of the interaction between three (iniparib, rucaparib, and olaparib) drugs and the protein, and validation of these parameters by typical frontal analysis. The numbers of binding sites on the column were (2.85 ± 0.05) × 10^-7, (1.89 ± 0.71) × 10^-6, and (1.49 ± 0.06) × 10^-7 M for iniparib, rucaparib, and olaparib, respectively. On these sites, the association constants of the three drugs to the protein were (9.85 ± 0.56) × 10⁴, (2.85 ± 0.34) × 10⁴, and (1.07 ± 0.35) × 10⁵ M^-1. The determined parameters presented a good agreement with the calculation by typical frontal analyses, which indicated that the current continuous competitive frontal analysis method was reliable for determining drug-protein interaction. Application of the methods was achieved by screening tubeimosides I and II as the bioactive compounds against breast cancer in Bolbostemma paniculatum. Their mechanism may be the interference of DNA repair via down-regulating PARP₁ and meiotic recombination 11 expressions, thus leading to oncogene mutations and death of cancer cells. The method was high speed since it allowed simultaneous determination of binding parameters between two drugs and a protein with a smaller number of experiments to be performed. Such a feature made the method an attractive alternative for high-speed analysis of drug-protein interaction or the other bindings in a binary system.

17 Mar 2023·The Oncologist

Phase II Trials of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Patients with Recurrent Ovarian Cancer

Article

Author: Penson, Richard T ; Bradley, Charles ; Konstantinopoulos, Panagiotis A ; Birrer, Michael J ; Matulonis, Ursula A ; Krasner, Carolyn N ; Whalen, Christin A ; Ambrosio, Allison J

AbstractBackgroundIniparib (BSI-201), a novel anticancer agent thought to have poly(ADP-ribose) polymerase (PARP) inhibitory activity and synergy with both gemcitabine and carboplatin (GC) was evaluated in 2 cohorts with GC.MethodsParallel multicenter, single-arm, phase II studies using a Simon two-stage design. Eligible patients had a histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma and demonstration of platinum-sensitive (≥6 months [mo]) or -resistant disease (relapse 2-6 mo post-platinum). Carboplatin (AUC 4 IV day 1), gemcitabine (1000 mg/m2 IV days 1 and 8), and iniparib (5.6 mg/kg IV days 1, 4, 8, and 11) were given on a 21-day cycle.ResultsThe overall response rate (ORR RECIST 1.0) in platinum sensitive disease was 66% (95% CI, 49-80) with a higher response rate in the 15 pts with germline BRCA mutations (gBRCAmut) (73%). Median PFS was 9.9 (95% CI, 8.2-11.3) months. In the platinum resistant population the ORR was 26% (95% CI, 14-42), however in the 11 pts for whom BRCA mutation was present, the best overall response was PR in 5 (46%). Median PFS was 6.8 months (range, 5.7-7.7 months). Notably, among the 17 CA-125-response-evaluable patients who did not achieve tumor response, 7 (41.2%) patients had a CA125 response, and 93% has clinical benefit (CR + PR + SD). The GCI combination was generally well tolerated despite a high incidence of thrombocytopenia and neutropenia, with no new toxicities.ConclusionsGiven the subsequent lack of efficacy demonstrated for iniparib in breast cancer, these are studies of GC and demonstrate a higher than traditionally appreciated activity in patients with platinum-sensitive and -resistant recurrent ovarian cancer, especially in patients that harbor a BRCA mutation, resetting the benchmark for efficacy in phase II trials. (ClinicalTrials.gov Identifiers: NCT01033292 & NCT01033123).

01 Sep 2022·Biochemical and Biophysical Research Communications

Crystal structures of the catalytic domain of human PARP15 in complex with small molecule inhibitors

Article

Author: Zhang, Jin ; Yang, Yang ; Zhong, Fanglin ; Zhou, Huan ; Xu, Qin ; Zhou, Xuelan ; Deng, Jun ; Li, Jian

PARP15, or ARTD7, is an enzyme carrying out mono-ADP-ribosylation and regulating activities of a range of cellular proteins. This enzyme belongs to the family of the poly(ADP-ribose) polymerases (PARPs), which comprises of proteins with various potential disease indications. Due to their involvement in a number of cellular processes and important role in DNA repair and regulation, PARPs have been considered attractive therapeutic targets over the past few years. The pursuit of small molecule PARP inhibitors has resulted in several FDA approved drugs for multiple cancers so far. As the use of PARP inhibitors as drug scaffolds is actively explored recently, there is increasing interest in the design of selective inhibitors based on the structural features of the PARP proteins. Here, we solved high-resolution crystal structures of the human PARP15 catalytic domain in complex with three marketed drugs of PARP inhibitors, which includes compounds 3-AB, iniparib and niraparib. The structures reported here contribute to our understanding of the ligand binding modes and structural features in the PARP15 catalytic domain, which can be employed to guide the rational design of selective inhibitors of PARPs.

1

News (Medical) associated with Iniparib

17 Jul 2009

·www.biospace.com

Sanofi-Aventis (France) and BiPar Sciences, Inc. Release: BSI-201 Enters Phase 3 in Metastatic Triple Negative Breast Cancer

PARIS and SOUTH SAN FRANCISCO, Calif., July 17, 2009 (GLOBE NEWSWIRE) -- Sanofi-aventis (EURONEXT:SAN) (NYSE:SNY) and its wholly owned subsidiary, BiPar Sciences, today announced the initiation of the pivotal Phase 3 trial for BSI-201 in combination with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC), defined by tumors lacking expression of estrogen, progesterone receptors and without over-expression of HER2. BSI-201 is a novel, investigational, targeted therapy which inhibits poly (ADP-ribose) polymerase (PARP1), an enzyme involved in DNA damage repair.

100 Deals associated with Iniparib

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External Link

KEGG	Wiki	ATC	Drug Bank
D09913	Iniparib	-	DB13877

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 3	ES	Sanofi	01 May 2012
Solid tumor	Phase 3	IT	Sanofi	01 May 2012
Solid tumor	Phase 3	BE	Sanofi	01 May 2012
Platinum-Sensitive Ovarian Carcinoma	Phase 3	US	Sanofi	01 Dec 2009
Recurrent Platinum-Resistant Ovarian Carcinoma	Phase 3	US	Sanofi	01 Dec 2009
Metastatic HER2-Negative Breast Carcinoma	Phase 3	US	Sanofi	01 Jul 2009
Ovarian Epithelial Carcinoma	Phase 3	US	Sanofi	01 Jun 2008
Primary peritoneal carcinoma	Phase 3	US	Sanofi	01 Jun 2008
Metastatic Triple-Negative Breast Carcinoma	Phase 3	US	Sanofi	01 Oct 2007
Uterine Carcinosarcoma	Discovery	US	Sanofi	01 May 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01045304 (Pubmed \| Breast Cancer Res) Manual	Phase 2	Triple Negative Breast Cancer ER negative \| HER2 negative \| PR negative	163	gemcitabine+carboplatin+iniparib (GC+w-iniparib)	(omugebznfa) = gxkelrcqdc qcrzgzralv (vkzvewfrgw, 23.9 - 44.4) View more	Negative	01 Sep 2019
NCT01045304 (Pubmed \| Breast Cancer Res) Manual	Phase 2		163	gemcitabine+carboplatin+iniparib (GC+tw-iniparib)	(omugebznfa) = wxlknybgzf qcrzgzralv (vkzvewfrgw, 19.7 - 39.6) View more	Negative	01 Sep 2019
NCT01173497 (TBCRC2016) Manual	Phase 2	Triple Negative Breast Cancer \| Brain metastases triple negative	37	Irinotecan Hydrochloride+Iniparib	(akhpmmnvmy) = zadmlppali ijyegcdrkt (hbqfgvljtv ) View more	-	18 May 2016
NCT00677079 (Pubmed \| Int J Gynecol Cancer) Manual	Phase 2	Platinum-Resistant Primary Peritoneal Carcinoma \| Ovarian Epithelial Carcinoma \| Fallopian Tube Carcinoma Last line BRCA1 Mutation \| BRCA2 Mutation	12	Iniparib	(wurryilvwq) = vlkpmhzafd uuhtwxfedf (uusktqazob )	Negative	01 Feb 2016
NCT01204125 (SOLTI NeoPARP, Pubmed \| Breast Cancer Res)	Phase 2	Triple Negative Breast Cancer Neoadjuvant	141	Paclitaxel alone	(axjruenvlu) = djoichikik kpuzxxnamm (teptfejeot ) View more	Negative	01 Nov 2015
NCT01204125 (SOLTI NeoPARP, Pubmed \| Breast Cancer Res)	Phase 2	Triple Negative Breast Cancer Neoadjuvant	141	Iniparib + Paclitaxel once-weekly	(axjruenvlu) = urfsufhnkt kpuzxxnamm (teptfejeot ) View more	Negative	01 Nov 2015
NCT00813956 (PrECOG 0105, Pubmed \| J Urol) Manual	Phase 2	Triple Negative Breast Cancer Neoadjuvant BRCA1 Mutation \| BRCA2 Mutation \| Triple-Negative	80	Gemcitabine+Carboplatin+Iniparib	(lmiuphohsv) = qklsdtskye lsbbuxkkqc (sjojphhxel, 27 - 46)	Positive	10 Jun 2015
NCT01086254 (Pubmed \| Ann Oncol)	Phase 2	metastatic non-small cell lung cancer First line	119	Gemcitabine-cisplatin	(vhpljtfsls) = uuwqmznery bzfllmfzrg (bqejbcghtq, 13.0% - 42.1%) View more	-	01 Nov 2014
NCT01086254 (Pubmed \| Ann Oncol)	Phase 2	metastatic non-small cell lung cancer First line	119	Gemcitabine-cisplatin-iniparib	(vhpljtfsls) = grxidpmfax bzfllmfzrg (bqejbcghtq, 11.9% - 30.4%) View more	-	01 Nov 2014
NCT01173497 (TBCRC 018, ASCO2013)	Phase 2	Triple Negative Breast Cancer	37	Iniparib + Irinotecan	vqcjhvbasj(pcplhnbnev) = ipubsjmopn reeyinkxhg (dnebacmirs ) View more	-	20 May 2013
NCT00687687 (Pubmed \| Obstet Gynecol Surv)	Phase 2	Uterine Carcinosarcoma	22	Iniparib plus paclitaxel and carboplatin	(gfcgeldgez) = tpnmcoljbz rngyfugucz (btqxbxtify, 8.5 - 46.1)	Negative	01 Sep 2012
NCT01033123 (ASCO2011)	Phase 2	Platinum-Sensitive Ovarian Carcinoma	41	Iniparib + GC	(krmawnudyv) = vexjorjzmz hntiqzzkts (fayuzefnvj )	-	20 May 2011
NCT00422682 (ASCO2011)	Phase 1	Non-Small Cell Lung Cancer	18	Iniparib	(fseajxcewc) = kvyudkcmrc ijzgysqxxt (jplcnxqidg )	-	20 May 2011