瑞马司他(Rebimastat) - 药物靶点：MMP1 x MMP14 x MMP2 x MMP8 x MMP9_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Rebimastat (USAN/INN)

+ [4]

靶点

MMP1 x MMP14 x MMP2 x MMP8 x MMP9

作用机制

MMP1抑制剂(基质金属蛋白酶-1抑制剂)、MMP14抑制剂(基质金属蛋白酶-14抑制剂)、MMP2抑制剂(基质金属蛋白酶-2抑制剂)

+ [2]

治疗领域

肿瘤呼吸系统疾病皮肤和肌肉骨骼疾病+ [3]

在研适应症-

非在研适应症

乳腺癌卡波西肉瘤非小细胞肺癌+ [1]

原研机构

Celltech Oy

在研机构-

非在研机构

Bristol Myers Squibb Co.Celltech Oy

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C23H41N5O5S

InChIKeyGTXSRFUZSLTDFX-HRCADAONSA-N

CAS号259188-38-0

关联

5

项与瑞马司他相关的临床试验

NCT00040755 / Completed临床2期IIT

Randomized Phase II Trial of BMS-275291 (NSC 713763, IND 62573) in Hormone Refractory Prostate Cancer

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

开始日期2002-05-01

申办/合作机构

National Cancer Institute

NCT00039104 / Completed临床2期IIT

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.

开始日期2002-04-01

申办/合作机构

National Cancer Institute

NCT00024024 / Completed临床1/2期IIT

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.

开始日期2001-08-01

申办/合作机构

National Cancer Institute

100 项与瑞马司他相关的临床结果

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100 项与瑞马司他相关的转化医学

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100 项与瑞马司他相关的专利（医药）

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23

项与瑞马司他相关的文献（医药）

2010-08-19·Oncogene1区 · 医学

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

1区 · 医学

Article

作者: 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).

2008-03-01·Cancer1区 · 医学

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

1区 · 医学

Article

作者: 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.

2007-10-01·Current Opinion in Supportive & Palliative Care4区 · 医学

Management of hormone refractory prostate cancer

4区 · 医学

Review

作者: 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 项与瑞马司他相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03800	-	-	DB06573

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
乳腺癌	临床3期	美国	Bristol Myers Squibb Co.	2002-05-13
卡波西肉瘤	临床3期	美国	-	-
非小细胞肺癌	临床3期	-	Celltech Oy	-
非小细胞肺癌	临床3期	-	Bristol Myers Squibb Co.	-
非小细胞肺癌	临床3期	美国	-	-
前列腺癌	临床3期	美国	-	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00006229 (BR.18, Pubmed \| J Urol)	临床3期	晚期非小细胞肺癌	774	BMS-275291	(觸鏇遞廠鏇製齋鹹選製) = 繭醖遞構鹹醖觸憲網製衊艱鑰顧憲衊膚鹽襯願 (醖製願蓋夢遞網窪衊範 ) 更多	不佳	2005-04-20
				Placebo	(觸鏇遞廠鏇製齋鹹選製) = 築齋鹹壓蓋願餘網顧餘衊艱鑰顧憲衊膚鹽襯願 (醖製願蓋夢遞網窪衊範 ) 更多
ASCO2004	临床2期	转移性去势抵抗性前列腺癌	80	BMS-275291 1200 mg po QD	網餘醖築製艱蓋鹹艱繭(鏇簾窪構餘鏇構夢網範) = 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 遞糧網壓構齋願鏇積製 (鏇鹹襯鹹糧繭鏇齋鬱鑰 ) 更多	-	2004-07-15
				BMS-275291 1200 mg po BID