Filanesib(Filanesib) - 药物靶点：KIF11_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Filanesib (USAN/INN)、Filanesib-hydrochloride

靶点

KIF11

作用机制

KIF11抑制剂(驱动蛋白-1抑制剂)

治疗领域

肿瘤免疫系统疾病心血管疾病+ [2]

在研适应症-

非在研适应症

急性髓性白血病晚期癌症晚期恶性实体瘤+ [5]

原研机构

Array BioPharma, Inc.

在研机构-

非在研机构

Array BioPharma, Inc.

Pfizer Inc.

Celgene Corp.

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)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C20H22F2N4O2S

InChIKeyLLXISKGBWFTGEI-FQEVSTJZSA-N

CAS号885060-09-3

关联

10

项与 Filanesib 相关的临床试验

NCT02384083

/ Completed临床1/2期IIT

Phase I/II, Multicenter, Open Label, Clinical Trial of Filanesib (ARRY-520) in Combination With Pomalidomide and Dexamethasone for Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients

Phase I/II, Multicenter, Open Label, Clinical Trial to evaluate safety and efficacy and determine the Maximum Tolerated Dose (MTD) of Filanesib in combination with pomalidomide and dexamethasone in relapsed/refractory (R/R) Multiple Myeloma (MM) patients

开始日期2015-09-01

申办/合作机构

Array BioPharma, Inc.

[+1]

EUCTR2014-001052-39-AT

/ Not yet recruitingN/A

The FACTOR Study (Filanesib and Carfilzomib Treatment of Relapsed/Refractory Multiple Myeloma):A Multinational, Randomized, Open-label Phase 3 Study of Filanesib (ARRY-520) +Carfilzomib Versus Single-agent Carfilzomib in Patients With Advanced Multiple Myeloma

开始日期2015-05-15

申办/合作机构

Array BioPharma, Inc.

EUCTR2014-002740-41-ES

/ Not yet recruiting临床1/2期IIT

Phase I/II, Multicenter, Open Label, Clinical Trial of Filanesib (ARRY-520) in combination with Pomalidomide and Dexamethasone for relapsed/refractory MM patients - POMDEFIL

开始日期2015-02-26

申办/合作机构-

100 项与 Filanesib 相关的临床结果

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100 项与 Filanesib 相关的转化医学

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100 项与 Filanesib 相关的专利（医药）

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34

项与 Filanesib 相关的文献（医药）

2024-03-01·Annals of Surgical Oncology

Cancer-Associated Fibroblasts Together with a Decline in CD8+ T Cells Predict a Worse Prognosis for Breast Cancer Patients

Article

作者: Noh, Yung-Kyun ; Pyo, Jung Soo ; Kim, Dong-Hoon ; Kim, Hyung Suk ; Lee, Jeong-Yeon ; Min, Kyueng-Whan ; Kwon, Mi Jung

BACKGROUNDCancer-associated fibroblasts (CAFs) play a crucial role in tumor microenvironment regulation and cancer progression. This study assessed the significance and predictive potential of CAFs in breast cancer prognosis.METHODSThe study included 1503 breast cancer patients. Cancer-associated fibroblasts were identified using morphologic features from hematoxylin and eosin slides. The study analyzed clinicopathologic parameters, survival rates, immune cells, gene sets, and prognostic models using gene-set enrichment analysis, in silico cytometry, pathway analysis, in vitro drug-screening, and gradient-boosting machine (GBM)-learning.RESULTSThe presence of CAFs correlated significantly with young age, lymphatic invasion, and perineural invasion. In silico cytometry showed altered leukocyte subsets in the presence of CAFs, with decreased CD8+ T cells. Gene-set enrichment analysis showed associations with critical processes such as the epithelial-mesenchymal transition and immune modulation. Drug sensitivity analysis in breast cancer cell lines with varying fibroblast activation protein-α expression suggested that CAF-targeted therapies might enhance the efficacy of certain anticancer drugs including ARRY-520, ispinesib-mesylate, paclitaxel, and docetaxel. Integrating CAF presence with machine-learning improved survival prediction. For breast cancer patients, CAFs were independent prognostic markers for worse disease-specific survival and disease-free survival.CONCLUSIONThis study highlighted the significance of CAFs in breast cancer biology and provided compelling evidence of their impact on patient outcomes and treatment response. The findings offer valuable insights into the potential of CAFs as prognostic and predictive biomarkers and support the development of CAF-targeted therapies to improve breast cancer management.

2022-08-01·Anti-Cancer Agents in Medicinal Chemistry4区 · 医学

Role of KSP Inhibitors as Anti-Cancer Therapeutics: An Update

4区 · 医学

Review

作者: Suvarna, Vasanti ; Chamariya, Rinkal

Abstract:Regardless of the growing discovery of anticancer treatments targeting cancer-specific pathways, cytotoxic therapy still maintained its abundant clinical significance because tumours harbor a greater population of actively dividing cells than normal tissues. Conventional anti-mitotic agents or microtubule poisons acting on the major mitotic spindle protein tubulin have been effectively used in clinical settings for cancer chemotherapy over the last three decades. However, the use of these drugs is associated with limited clinical utility due to serious side effects such as debilitating and dose-limiting peripheral neuropathy, myelosuppression, drug resistance, and allergic reactions. Therefore, research initiatives have been undertaken to develop novel microtubule motor proteins inhibitors that can potentially circumvent the limitations associated with conventional microtubule poisons. Kinesin spindle proteins (KSP) belonging to the kinesin-5 family play a crucial role during mitosis and unregulated cell proliferation. Evidence from preclinical studies and different phases of clinical trials have presented kinesin spindle protein as a promising target for cancer therapeutics. Kinesin spindle protein inhibitors causing mitosis disruption without interfering with microtubule dynamics in non-dividing cells offer a potential therapeutic alternative for the management of several major cancer types and are devoid of side effects associated with classical anti-mitotic drugs. This review summarizes recent data highlighting progress in the discovery of targeted KSP inhibitors and presents the development of scaffolds, structure-activity relationships, and outcomes of biological and enzyme inhibition studies. We reviewed the recent literature reports published over the last decade, using various electronic database searches such as PubMed, Embase, Medline, Web of Science, and Google Scholar. Clinical trial data till 2021 was retrieved from ClinicalTrial.gov. Major chemical classes developed as selective KSP inhibitors include dihydropyrimidines, β-carbolines, carbazoles, benzimidazoles, fused aryl derivatives, pyrimidines, fused pyrimidines, quinazolines, quinolones, thiadiazolines, spiropyran, and azobenzenes. Drugs such as filanesib, litronesib, ispinesib have entered clinical trials; the most advanced phase explored is Phase II. KSP inhibitors have exhibited promising results; however, continued exploration is greatly required to establish the clinical potential of KSP inhibitors.

2022-03-29·ACS Omega3区 · 化学

Effective Synthesis and Biological Evaluation of Natural and Designed Bis(indolyl)methanes via Taurine-Catalyzed Green Approach

3区 · 化学

ArticleOA

作者: Shukla, Manjari ; Erande, Rohan D. ; Chavan, Kailas A. ; Bhattacharyya, Sudipta ; Mali, Ghanshyam ; Maji, Sushobhan ; Chauhan, Amar Nath Singh

An ecofriendly, inexpensive, and efficient route for synthesizing 3,3'-bis(indolyl)methanes (BIMs) and their derivatives was carried out by an electrophilic substitution reaction of indole with structurally divergent aldehydes and ketones using taurine and water as a green catalyst and solvent, respectively, under sonication conditions. Using water as the only solvent, the catalytic process demonstrated outstanding activity, productivity, and broad functional group tolerance, affording the required BIM natural products and derivatives in excellent yields (59-90%). Furthermore, in silico based structure activity analysis of the synthesized BIM derivatives divulges their potential ability to bind antineoplastic drug target and spindle motor protein kinesin Eg5. The precise binding mode of BIM derivatives with the ATPase motor domain of Eg5 is structurally reminiscent with previously reported allosteric inhibitor Arry520, which is under phase III clinical trials. Nevertheless, detailed analysis of the binding poses indicates that BIM derivatives bind the allosteric pocket of the Eg5 motor domain more robustly than Arry520; moreover, unlike Arry520, BIM binding is found to be resistant to drug-resistant mutations of Eg5. Accordingly, a structure-guided mechanism of Eg5 inhibition by synthesized BIM derivatives is proposed.

100 项与 Filanesib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11754	Filanesib	-	DB06040

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3期	捷克	Array BioPharma, Inc.	-
多发性骨髓瘤	临床3期	德国	Array BioPharma, Inc.	-
多发性骨髓瘤	临床3期	英国	Array BioPharma, Inc.	-
多发性骨髓瘤	临床1期	英国	Array BioPharma, Inc.	-
多发性骨髓瘤	临床1期	德国	Array BioPharma, Inc.	-
多发性骨髓瘤	临床1期	西班牙	Array BioPharma, Inc.	-
多发性骨髓瘤	临床1期	西班牙	Array BioPharma, Inc.	-
多发性骨髓瘤	临床1期	匈牙利	Array BioPharma, Inc.	-
多发性骨髓瘤	临床1期	匈牙利	Array BioPharma, Inc.	-
多发性骨髓瘤	临床1期	捷克	Array BioPharma, Inc.	-

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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


NCT02384083 (Pomdefil, Pubmed \| Br J Haematol)	临床2期	多发性骨髓瘤 alpha 1-acid glycoprotein (AAG)	-	Filanesib + Pomalidomide + Dexamethasone	(願醖網淵鹽淵網繭壓壓) = 憲積淵築襯積鹽窪蓋製鏇衊鑰鏇繭選鑰構積衊 (鏇夢顧鑰衊淵鹽廠廠衊 ) 更多	积极	2021-02-01
NCT01372540 (Pubmed) 人工标引	临床1期	复发性多发性骨髓瘤二线	63	Dexamethasone+filanesib+carfilzomib (Part A)	(膚夢範齋淵壓窪範願衊) = Among 30 patients treated at the MTD for the Part A dose-expansion cohorts with filanesib 1.5 mg/m2, carfilzomib 20/27 mg/m2, and dexamethasone 4 mg,A total of 14 patients were treated at the MTD for the Part B dose-expansion cohort with filanesib 1.5 mg/m2, carfilzomib 20/56 mg/m2, and dexamethasone (4 mg prior to each carfilzomib dose in 10 patients and 40 mg on days 1, 8, and 15 in 4 patients due to protocol amendment) 鏇壓築膚淵窪衊衊構鬱 (繭觸觸餘觸膚顧遞窪構 ) 更多	积极	2019-10-01
				Dexamethasone+filanesib+carfilzomib (Part B)
NCT00821249 (Pubmed) 人工标引	临床1/2期	多发性骨髓瘤	-	Dexamethasone+Empegfilgrastim+Filanesib	(網積膚膚獵夢鏇構鏇製) = 範糧衊衊憲鏇獵顧艱鑰顧簾築鏇壓製積糧獵壓 (衊範襯餘築範膚繭壓鑰 ) 更多	积极	2017-12-01
				Filanesib plus dexamethasone	-
NCT01989325 (EHA2015)	临床2期	复发性多发性骨髓瘤	247	Filanesib (Patients with low AAG)	(製繭衊顧餘膚廠鏇鬱襯) = 鬱觸齋窪襯構繭範鹽蓋艱構窪齋醖顧齋憲鏇選 (範鬱廠網選構憲遞簾憲 )	-	2015-05-21
				Filanesib (Patients with high AAG)	(製繭衊顧餘膚廠鏇鬱襯) = 衊網簾觸淵簾蓋窪廠選艱構窪齋醖顧齋憲鏇選 (範鬱廠網選構憲遞簾憲 )
NCT00462358 (Pubmed \| Invest New Drugs) 人工标引	临床1期	实体瘤	41	filanesib (Initial Schedules)	(壓選糧構齋齋繭範選鬱) = 鏇觸醖糧鬱淵蓋製製製鹽膚壓積網蓋夢餘鑰鹹 (鏇築願遞壓膚衊餘餘觸 )	积极	2015-04-01
				filanesib (Alternate Schedules)	(壓選糧構齋齋繭範選鬱) = 衊蓋鏇壓窪鬱範憲廠襯鹽膚壓積網蓋夢餘鑰鹹 (鏇築願遞壓膚衊餘餘觸 )
NCT00637052 (Pubmed \| Cancer)	临床1期	难治性白血病 KSP inhibition	36	ARRY-520	(壓鏇廠鏇淵壓積遞鑰鹹) = 壓壓繭鹹顧築網憲艱夢餘鏇遞齋願糧齋窪觸繭 (製選選壓夢淵廠獵憲齋 )	不佳	2012-07-15
ASCO2010	临床1期	实体瘤	34	ARRY-520	(糧衊構壓夢獵廠繭繭憲) = 繭壓築遞壓願憲簾衊範鏇遞顧願製憲餘壓鬱鏇 (繭壓膚淵鬱顧夢淵鏇齋 ) 更多	-	2010-05-20
ASCO2009	临床1期	白血病	15	ARRY-520	(壓壓鏇壓繭構壓繭膚齋) = 襯構廠鹹鬱鏇憲觸蓋簾鹹鑰繭憲觸襯廠選餘膚 (鬱觸簾繭顧獵壓簾獵積 )	-	2009-05-20