Delving into the Latest Updates on Rebimastat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Rebimastat (USAN/INN)

+ [4]

Target

MMP1 x MMP14 x MMP2 x MMP8 x MMP9

Mechanism

MMP1 inhibitors(Matrix metalloproteinase-1 inhibitors), MMP14 inhibitors(Matrix metalloproteinase 14 inhibitors), MMP2 inhibitors(Matrix metalloproteinase-2 inhibitors)

+ [2]

Therapeutic Areas

NeoplasmsRespiratory DiseasesSkin and Musculoskeletal Diseases+ [3]

Active Indication-

Inactive Indication

Breast CancerKaposi SarcomaNon-Small Cell Lung Cancer+ [1]

Originator Organization

Celltech Oy

Active Organization-

Inactive Organization

Bristol Myers Squibb Co.Celltech Oy

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC23H41N5O5S

InChIKeyGTXSRFUZSLTDFX-HRCADAONSA-N

CAS Registry259188-38-0

BMS-275291 may stop the growth of prostate cancer by stopping blood flow to the tumor and by blocking the enzymes necessary for tumor cell growth. Randomized phase II trial to study the effectiveness of BMS-275291 in treating patients who have prostate cancer that has not responded to hormone therapy

Start Date01 May 2002

Sponsor / Collaborator

National Cancer Institute

NCT00039104 / CompletedPhase 2IIT

A Phase II, Open-Label, Randomized Trial of Zoledronic Acid (Zometa™) and BMS-275291 (NSC#713763) in Patients With Hormone Refractory Prostate Cancer

Phase II trial to study the effectiveness of combining zoledronate with BMS-275291 in treating patients who have prostate cancer that has not responded to previous hormone therapy. Zoledronate may prevent bone loss and stop the growth of tumor cells in bone. BMS-275291 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Combining zoledronate with BMS-275291 may kill more tumor cells.

Start Date01 Apr 2002

Sponsor / Collaborator

National Cancer Institute

NCT00024024 / CompletedPhase 1/2IIT

A Phase I-II Trial Of BMS-275291 In Patients With HIV-Related Kaposi's Sarcoma

Phase I/II trial to study the effectiveness of BMS-275291 in treating patients who have HIV-related Kaposi's sarcoma. Drugs such as BMS-275291 may stop the growth of Kaposi's sarcoma by stopping blood flow to the tumor.

Start Date01 Aug 2001

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Rebimastat

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100 Translational Medicine associated with Rebimastat

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100 Patents (Medical) associated with Rebimastat

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23

Literatures (Medical) associated with Rebimastat

19 Aug 2010·OncogeneQ1 · MEDICINE

Lovastatin inhibits EGFR dimerization and AKT activation in squamous cell carcinoma cells: potential regulation by targeting rho proteins

Q1 · MEDICINE

Article

Author: J Dimitroulakos ; K Ding ; B G Le Francois ; G Goss ; P A Bradbury ; T T Zhao

We recently showed the ability of lovastatin to inhibit the function of the epidermal growth factor receptor (EGFR) and its downstream signaling of the phosphatidylinositol-3 kinase/AKT pathway. Combining lovastatin with gefitinib, a potent EGFR inhibitor, induced synergistic cytotoxicity in various tumor-derived cell lines. In this study, lovastatin treatment was found to inhibit ligand-induced EGFR dimerization in squamous cell carcinoma cells and its activation of AKT and its downstream targets 4E-binding protein 1 and S6 kinase 1. This inhibition was associated with global protein translational inhibition shown by a decrease in RNA associated polysome fractions. The effects of lovastatin on EGFR function were reversed by the addition of geranylgeranyl pyrophosphate, which functions as a protein membrane anchor. Lovastatin treatment induced actin cytoskeletal disorganization and the expression of geranylgeranylated rho family proteins that regulate the actin cytoskeleton, including rhoA. Lovastatin-induced rhoA was inactive as EGF stimulation failed to activate rhoA and inhibition of the rho-associated kinase, a target and mediator of rhoA function, with Y-27632 also showed inhibitory effects on EGFR dimerization. The ability of lovastatin to inhibit EGFR dimerization is a novel exploitable mechanism regulating this therapeutically relevant target. To explore the potential clinical significance of this combination, we evaluated the effect of statin on the overall survival (OS) and disease-specific survival (DSS) of patients with advanced non-small-cell lung cancer enrolled in the NCIC Clinical Trials Group phase III clinical trials BR21 (EGFR tyrosine kinase inhibitor erlotinib versus placebo) and BR18 (carboplatin and paclitaxel with or without the metalloproteinase inhibitor BMS275291). In BR18, use of statin did not affect OS or DSS. In BR21, patients showed a trend for improvement in OS (HR: 0.69, P=0.098) and DSS (HR: 0.62, P=0.048), but there was no statin x treatment interaction effect (P=0.34 and P=0.51 for OS and DSS, respectively).

01 Mar 2008·CancerQ1 · MEDICINE

Phase 1/2 trial of BMS‐275291 in patients with human immunodeficiency virus‐related Kaposi sarcoma

Q1 · MEDICINE

Article

Author: Lawrence D. Kaplan ; Jamie H. Von Roenn ; Jeannette Y. Lee ; Amy Chadburn ; Brett T. Brinker ; Ethel Cesarman ; Susan E. Krown ; David H. Henry

AbstractBACKGROUND.Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS‐275291, was evaluated in patients with human immunodeficiency virus‐associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored.METHODS.Cohorts of 6 patients were to be treated with BMS‐275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose‐limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response.RESULTS.Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3–54 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation/de‐escalation decisions utilizing the apoptosis assay was not feasible.CONCLUSIONS.BMS‐275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better‐tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus‐associated KS. The apoptosis assay was not helpful in predicting response. Cancer 2008. © 2008 American Cancer Society.

01 Oct 2007·Current Opinion in Supportive & Palliative CareQ4 · MEDICINE

Management of hormone refractory prostate cancer

Q4 · MEDICINE

Review

Author: Small, Eric J ; Lin, Amy M

PURPOSE OF REVIEWThis review highlights the most interesting developments and outstanding issues surrounding the management of hormone-refractory prostate cancer published in the medical literature during the past year.RECENT FINDINGSRecent research has reported poor health-related quality-of-life outcomes for patient with hormone-refractory prostate cancer treated in standard clinical practices. In addition, age-related differences in survival appear to exist for patients with hormone-refractory prostate cancer. Two potential future therapies for hormone-refractory prostate cancer, sipuleucel-T and the combination regimen of docetaxel and DN-101, demonstrate promising preliminary clinical data in terms of improving survival while minimizing toxicity. A variety of novel agents has been tested for hormone-refractory prostate cancer, including pertuzumab and BMS-275291, which may stabilize disease with minimal toxicity. In terms of bone-related health, skeletal-related events have been found to be associated with worse survival and health-related quality of life outcomes.SUMMARYData reported during the past year have implications for future research directions. This direction includes the need for continued exploration of health-related quality of life and age-related outcomes, further study of the disease-stabilizing effects of novel therapies and their translation into improved survival, as well as directed efforts to continue preventing skeletal-related events, which may impact survival and health-related quality of life.

100 Deals associated with Rebimastat

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External Link

KEGG	Wiki	ATC	Drug Bank
D03800	-	-	DB06573

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 3	US	Bristol Myers Squibb Co.	13 May 2002
Kaposi Sarcoma	Phase 3	US	-	-
Non-Small Cell Lung Cancer	Phase 3	-	Celltech Oy	-
Non-Small Cell Lung Cancer	Phase 3	-	Bristol Myers Squibb Co.	-
Non-Small Cell Lung Cancer	Phase 3	US	-	-
Prostatic Cancer	Phase 3	US	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00006229 (BR.18, Pubmed \| J Urol)	Phase 3	Advanced Lung Non-Small Cell Carcinoma	774	BMS-275291	(fydincuabu) = mqmbanfakr ypiznutcvk (axcjkwrsmj ) View more	Negative	20 Apr 2005
				Placebo	(fydincuabu) = djcdlvcbqi ypiznutcvk (axcjkwrsmj ) View more
ASCO2004	Phase 2	Metastatic castration-resistant prostate cancer	80	BMS-275291 1200 mg po QD	jwtifzercs(sbkhllksyw) = Mean pre/post change in PSA slopes was 0.0018 (p=0.3), equivalent to an increase in PSA doubling time from 70 to 86 days kdzmsurfow (oombllmktz ) View more	-	15 Jul 2004
				BMS-275291 1200 mg po BID