Delanzomib(Delanzomib) - 药物靶点：Proteasome_在研适应症：多发性骨髓瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Delanzomib (USAN)

+ [7]

靶点

Proteasome

作用机制

蛋白酶体抑制剂、细胞凋亡刺激剂

治疗领域

肿瘤免疫系统疾病心血管疾病+ [1]

在研适应症

多发性骨髓瘤

非在研适应症

晚期恶性实体瘤系统性红斑狼疮

原研机构

Teva Pharmaceutical Industries Ltd.

在研机构

Institute For Myeloma & Bone Cancer Research

非在研机构

Cephalon, Inc.

EOS (Ethical Oncology Science)

最高研发阶段临床前

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C21H28BN3O5

InChIKeySJFBTAPEPRWNKH-CCKFTAQKSA-N

CAS号847499-27-8

关联

3

项与 Delanzomib 相关的临床试验

NCT01348919 / Completed临床1/2期

An Open-Label Study to Determine the Maximum Tolerated Dose and Evaluate the Safety and Efficacy of CEP-18770 in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-18770 in combination with lenalidomide and dexamethasone in participants with relapsed or refractory multiple myeloma.

开始日期2011-08-03

申办/合作机构

Teva Branded Pharmaceutical Products R&D, Inc.

NCT01023880 / Terminated临床1/2期

An Open-Label Study to Determine the Maximum Tolerated Dose and Evaluate the Efficacy and Safety of CEP-18770 in Patients With Relapsed Multiple Myeloma Refractory to the Most Recent Therapy

The primary objective for part 1 of the study is to determine the maximum tolerated dose (MTD) of CEP-18770 in patients with relapsed and refractory multiple myeloma. The primary objective for part 2 is to evaluate the antitumor activity of CEP-18770 in patients treated at the MTD.

开始日期2010-01-01

申办/合作机构

Cephalon, Inc.

NCT00572637 / Completed临床1期

An Open-Label, Dose-escalation, Phase I Study to Determine the Maximum Tolerated Dose, Recommended Dose, Pharmacokinetics, and Pharmacodynamics of the Proteosome Inhibitor CEP 18770 Given Intravenously as Single Agent in Patients With Advanced Solid Tumours or Non-Hodgkin's Lymphomas

This Phase 1 escalating-dose study is designed to assess, the safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel proteasome inhibitor CEP 18770, given intravenously as single agent, in patients with advanced, incurable solid tumours or NHL, and to identify the recommended dose of CEP 18770 to be used in Phase 2 studies.

开始日期2007-11-01

申办/合作机构

EOS (Ethical Oncology Science)

100 项与 Delanzomib 相关的临床结果

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100 项与 Delanzomib 相关的转化医学

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100 项与 Delanzomib 相关的专利（医药）

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39

项与 Delanzomib 相关的文献（医药）

2023-02-01·Biological and Pharmaceutical Bulletin

Potential Efficacy of Proteasome Inhibitor, Delanzomib, for the Treatment of Renal Fibrosis

Article

作者: Yamada, Yoshihisa ; Nagao, Goshi ; Ishida, Tatsuhiro ; Hattori, Katsuji ; Sawa-Aihara, Ayano

Renal fibrosis is scarring and tissue hardening caused by the excess deposition of extracellular matrix proteins in response to chronic inflammation. Renal fibrosis is the primary cause of a progressive loss of renal function, and is an important therapeutic target because it ultimately leads to end-stage renal failure, which can be treated only by either dialysis or kidney transplantation. There is no effective treatment that specifically targets renal fibrosis. Myofibroblasts are known to evade apoptosis by activating molecular mechanisms in response to pro-survival biomechanical and growth factor signals from the fibrotic microenvironment. In this study, we screened and selected compounds that selectively cause cell death in myofibroblasts in vitro and studied their possible potency against renal fibrosis in a mouse model. Several proteasome inhibitors induced selective cell death in myofibroblasts differentiated from the human fibroblast cell line (MRC5). The in vivo antifibrotic effect of Delanzomib (Dz), one of the proteasome inhibitors most sensitive to myofibroblasts in vitro, was investigated in a Unilateral Ureteric Obstruction (UUO) mouse model. Treatment with Dz decreased the expression levels of the actin-alpha-2 (ACTA2) and collagen-type-1-alpha-1 (COL1A1) genes in the kidney, which are common fibrosis markers. These results suggest that Dz might be a compound that suppresses renal fibrosis by inducing selective cell death of myofibroblasts, although further investigation is required.

2023-01-01·Frontiers in chemistry

Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies.

Article

作者: Sherif, Asmaa E ; Ghaboosh, Hiba ; Mahgoub, Mohanad A ; Ashour, Ahmed ; Abdelmoniem, Nihal ; Edris, Alaa ; Samman, Waad A ; Garelnabi, Elrashied A E ; Mukhtar, Rua M ; Ibrahim, Sabrin R M ; Mohamed, Gamal A ; Bafail, Rawan ; Osman, Wadah ; Ghazawi, Kholoud F ; Alzain, Abdulrahim A ; Alhaddad, Aisha A ; Elrufaie, Hisham A

Tropomyosin-receptor kinase A (TrkA) is the primary isoform among the tropomyosin-receptor kinases that have been associated with human cancer development, contributing to approximately 7.4% of all cancer cases. TrkA represents an attractive target for cancer treatment; however, currently available TrkA inhibitors face limitations in terms of resistance development and potential toxicity. Hence, the objective of this study was to identify new allosteric-approved inhibitors of TrkA that can overcome these challenges and be employed in cancer therapy. To achieve this goal, a screening of 9,923 drugs from the ChEMBL database was conducted to assess their repurposing potential using molecular docking. The top 49 drug candidates, exhibiting the highest docking scores (-11.569 to -7.962 kcal/mol), underwent MM-GBSA calculations to evaluate their binding energies. Delanzomib and tibalosin, the top two drugs with docking scores of -10.643 and -10.184 kcal/mol, respectively, along with MM-GBSA dG bind values of -67.96 and -50.54 kcal/mol, were subjected to 200 ns molecular dynamic simulations, confirming their stable interactions with TrkA. Based on these findings, we recommend further experimental evaluation of delanzomib and tibalosin to determine their potential as allosteric inhibitors of TrkA. These drugs have the potential to provide more effective and less toxic therapeutic alternatives. The approach employed in this study, which involves repurposing drugs through molecular docking and molecular dynamics, serves as a valuable tool for identifying novel drug candidates with distinct therapeutic uses. This methodology can contribute to reducing the attrition rate and expediting the process of drug discovery.

2023-01-01·Frontiers in endocrinology

Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?

Review

作者: Modica, Roberta ; Grossrubatscher, Erika Maria ; Fanciulli, Giuseppe ; Florio, Tullio ; Veresani, Alessandro ; Colao, Annamaria ; Ferraù, Francesco ; Russo, Flaminia ; La Salvia, Anna ; Faggiano, Antongiulio

IntroductionMedullary thyroid cancer (MTC) is a rare thyroid tumour whose management in advanced stages is challenging, despite effective therapeutic options having expanded in recent years. Proteasome inhibitors (PrIn) have shown the ability to improve patient outcomes, including survival and quality of life, in several malignancies, due to their ability to impair cell proliferation and cause apoptosis through the inhibition of the proteasome activity. Consequently, these drugs could represent a useful tool, alone or in combination with other treatments, in MTC patients.Aim of the studyThis review aims to summarize the available in vitro and in vivo data about the role of PrIn in MTC.Materials and methodsWe performed an extensive search for relevant data sources, including full-published articles in international online databases (PubMed, Web of Science, Scopus), preliminary reports in selected international meeting abstract repositories, and short articles published as supplements of international meetings, by using the following terms: medullary thyroid carcinoma, proteasome inhibitors, bortezomib, carfilzomib, ixazomib, delanzomib, marizomib, oprozomib, and MG132. Additionally, we conducted with the same keywords, an in-depth search in registered clinical trials repositories.ResultsOur search revealed in vitro studies in human and murine MTC cell lines, based on the use of PrIns, both alone and in combination with other anticancer drugs, and two pertinent clinical trials.ConclusionWe found a strong discrepancy between the evidence of PrIns effects in preclinical studies, and the scarcity or early interruption of clinical trials. We might speculate that difficulties in enrolling patients, as happens in other rare diseases, may have discouraged trials' implementation in favor of drugs already approved for MTC. However, given the concrete improvement in the comprehension of the molecular basis of PrIn effects in MTC, new clinical trials with accurate inclusion criteria of enrollment might be warranted, in order to ascertain whether this treatment, alone or in combination with other drugs, could indeed represent an option to enhance the therapeutic response, and to ultimately improve patients' outcome and survival.

100 项与 Delanzomib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10110	-	-	DB11956

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
多发性骨髓瘤	临床前	美国	Cephalon, Inc.	2010-01-01
晚期恶性实体瘤	药物发现	意大利	EOS (Ethical Oncology Science)	2007-11-01
晚期恶性实体瘤	药物发现	瑞士	EOS (Ethical Oncology Science)	2007-11-01
非霍奇金淋巴瘤	药物发现	瑞士	EOS (Ethical Oncology Science)	2007-11-01
非霍奇金淋巴瘤	药物发现	意大利	EOS (Ethical Oncology Science)	2007-11-01
系统性红斑狼疮	药物发现	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


NCT01348919 (CTgov)	临床1/2期	浆细胞骨髓瘤难治	11	Lenalidomide+CEP-18770+Dexamethasone (CEP-18770 Dose B)	蓋獵膚製齋鹹鬱壓齋簾(窪簾鑰顧鹽構糧網艱簾) = 襯窪鹹範醖餘鏇廠壓繭繭蓋構簾選衊網選製構 (簾襯繭壓衊範衊醖獵築, 願範鏇鏇糧願夢簾構獵 ~ 餘觸遞壓願積積網廠廠) 更多	-	2023-06-28
				Lenalidomide+CEP-18770+Dexamethasone (CEP-18770 Dose A)	鹽餘鹽壓糧遞觸觸憲範(構鹽遞壓構範窪選鹹繭) = 壓廠衊鹽構製艱簾夢範範鏇顧艱淵窪襯繭糧襯 (鏇繭窪窪廠襯窪齋積襯, 獵製鹹築築築製簾鬱襯 ~ 鹽憲夢壓範齋壓窪積夢) 更多
NCT01023880 (Pubmed \| Leukemia) 人工标引	临床1/2期	多发性骨髓瘤	105	Delanzomib (during dose escalation)	(願鹹鬱鑰膚鹹襯積鏇選) = 遞積淵壓願製夢夢製蓋觸餘獵範夢衊艱製觸齋 (獵製遞膚鹽餘構獵積繭 ) 更多	不佳	2017-08-01
				Delanzomib (expansion cohort)	(願鹹鬱鑰膚鹹襯積鏇選) = 鏇糧選憲窪鬱獵簾顧糧觸餘獵範夢衊艱製觸齋 (獵製遞膚鹽餘構獵積繭 ) 更多