Efatutazone hydrochloride(Efatutazone hydrochloride) - 药物靶点：PPARγ_在研适应症：粘液样脂肪肉瘤，甲状腺未分化癌，甲状腺癌复发_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Efatutazone、Inolitazone

+ [2]

靶点

PPARγ

作用机制

PPARγ激动剂(过氧化物酶体增长因子活化受体γ激动剂)

治疗领域

肿瘤内分泌与代谢疾病其他疾病

在研适应症

粘液样脂肪肉瘤甲状腺未分化癌甲状腺癌复发

非在研适应症

晚期癌症晚期非小细胞肺癌结直肠癌+ [4]

原研机构

Daiichi Sankyo Co., Ltd.

在研机构

Daiichi Sankyo, Inc.

非在研机构

Daiichi Sankyo Co., Ltd.

最高研发阶段临床2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C27H29ClN4O5S

InChIKeyJYVSNMNBGHMWQB-UHFFFAOYSA-N

CAS号1048002-36-3

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关联

17

项与 Efatutazone hydrochloride 相关的临床试验

NCT02249949 / Completed临床2期IIT

A Phase II Study of the Peroxisome Proliferator-Activated Receptor Gamma Agonist, Efatutazone in Patients With Previously Treated, Unresectable Myxoid Liposarcoma

This phase II trial studies how well efatutazone dihydrochloride works in treating patients with previously treated myxoid liposarcoma that cannot be removed by surgery. Drugs used in chemotherapy, such as efatutazone dihydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

开始日期2014-10-01

申办/合作机构

Alliance Foundation Trials LLC

[+2]

NCT02152137 / Completed临床2期IIT

A Phase 2 Study of Efatutazone, an Oral PPAR Agonist, In Combination With Paclitaxel in Patients With Advanced Anaplastic Thyroid Cancer

This phase II trial studies how well inolitazone dihydrochloride (efatutazone dihydrochloride) and paclitaxel work in treating patients with anaplastic thyroid cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Drugs used in chemotherapy, such as efatutazone dihydrochloride and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

开始日期2014-09-01

申办/合作机构

Alliance Foundation Trials LLC

[+2]

NCT01504490 / Terminated临床1期IIT

A Phase I Study of a Combination of the Proteosome Proliferator-Activated Receptor Gamma Agonist, CS-7017 and the Retinoid X Receptor Agonist, Bexarotene

This study is for patients with advanced solid tumors. The purpose of this study is to test the safety and effectiveness of a new combination of drugs, CS-7017 and Bexarotene in patients with advanced cancer. CS-7017 and Bexarotene both have many effects on cancer cells, including stopping cancer cells from growing and dividing, and causing the cancer cells to die. CS-7017 and Bexarotene work on cancer cells in a similar manner and both drugs together may have an even greater effect against cancer cells, hopefully, increasing the killing of cancer cells.
CS-7017 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in any type of cancer. Bexarotene is an anti-cancer agent that has been approved by the FDA for patients with a specific type of cancer, cutaneous T-cell lymphoma.
This study will help find out what effects the combination of drugs, CS-7017 and Bexarotene, has on cancer. This research is being done because it is not known if CS-7017 is safe to be given with Bexarotene.

开始日期2011-12-01

申办/合作机构

Georgetown University

[+1]

100 项与 Efatutazone hydrochloride 相关的临床结果

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100 项与 Efatutazone hydrochloride 相关的转化医学

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100 项与 Efatutazone hydrochloride 相关的专利（医药）

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22

项与 Efatutazone hydrochloride 相关的文献（医药）

2023-08-13·Journal of Biomolecular Structure and Dynamics

In-silico discovery of inhibitors against human papillomavirus E1 protein

Article

作者: Hwang, Siaw San ; Rahman, Taufiq ; Wezen, Xavier Chee ; Gunasinghe, Juliyan ; Yam, Wai Keat

High-risk (HR) Human papillomavirus (e.g. HPV16 and HPV18) causes approximately two-thirds of all cervical cancers in women. Although the first and second-generation vaccines confer some protection against individuals, there are no approved drugs to treat HR-HPV infections to-date. The HPV E1 protein is an attractive drug target because the protein is highly conserved across all HPV types and is crucial for the regulation of viral DNA replication. Hence, we used the Random Forest algorithm to construct a Quantitative-Structure Activity Relationship (QSAR) model to predict the potential inhibitors against the HPV E1 protein. Our QSAR classification model achieved an accuracy of 87.5%, area under the receiver operating characteristic curve of 1.00, and F-measure of 0.87 when evaluated using an external test set. We conducted a drug repurposing campaign by deploying the model to screen the Drugbank database. The top three compounds, namely Cinalukast, Lobeglitazone, and Efatutazone were analyzed for their cell membrane permeability, toxicity, and carcinogenicity. Finally, these three compounds were subjected to molecular docking and 200 ns-long Molecular Dynamics (MD) simulations. The predicted binding free energies for the candidates were calculated using the MM-GBSA method. The binding free energies for Cinalukast, Lobeglitazone, and Efatutazone were -37.84 kcal/mol, -25.30 kcal/mol, and -29.89 kcal/mol respectively. Therefore, we propose their chemical scaffolds for future rational design of E1 inhibitors.Communicated by Ramaswamy H. Sarma.

2021-08-15·Cancer Research1区 · 医学

An AIB1 Isoform Alters Enhancer Access and Enables Progression of Early-Stage Triple-Negative Breast Cancer

1区 · 医学

Article

作者: Riegel, Anna T. ; Loudig, Olivier ; Pearson, Gray W. ; Kushner, Max H. ; Kietzman, William B. ; Graham, Garrett T. ; Schmidt, Marcel O. ; Wellstein, Anton ; Sengupta, Surojeet ; Sharif, Ghada M. ; Campbell, Moray J. ; Nasir, Apsra ; Fineberg, Susan

AbstractAIB1Δ4 is an N-terminally truncated isoform of the oncogene amplified in breast cancer 1 (AIB1) with increased expression in high-grade human ductal carcinoma in situ (DCIS). However, the role of AIB1Δ4 in DCIS malignant progression has not been defined. Here we CRISPR-engineered RNA splice junctions to produce normal and early-stage DCIS breast epithelial cells that expressed only AIB1Δ4. These cells showed enhanced motility and invasion in 3D cell culture. In zebrafish, AIB1Δ4-expressing cells enabled invasion of parental cells when present in a mixed population. In mouse xenografts, a subpopulation of AIB1Δ4 cells mixed with parental cells enhanced tumor growth, recurrence, and lung metastasis. AIB1Δ4 chromatin immunoprecipitation sequencing revealed enhanced binding to regions including peroxisome proliferator-activated receptor (PPAR) and glucocorticoid receptor (GR) genomic recognition sites. H3K27ac and H3K4me1 genomic engagement patterns revealed selective activation of breast cancer-specific enhancer sites by AIB1Δ4. AIB1Δ4 cells displayed upregulated inflammatory response genes and downregulated PPAR signaling gene expression patterns. In the presence of AIB1Δ4 enabler cells, parental cells increased NF-κB and WNT signaling. Cellular cross-talk was inhibited by the PPARγ agonist efatutazone but was enhanced by treatment with the GR agonist dexamethasone. In conclusion, expression of the AIB1Δ4-selective cistrome in a small subpopulation of cells triggers an “enabler” phenotype hallmarked by an invasive transcriptional program and collective malignant progression in a heterogeneous tumor population.Significance:A minor subset of early-stage breast cancer cells expressing AIB1Δ4 enables bulk tumor cells to become invasive, suggesting that selective eradication of this population could impair breast cancer metastasis.

2020-12-01·Thyroid Research

Recent advances in the management of anaplastic thyroid cancer

Review

作者: Fugazzola, Laura ; De Leo, Simone ; Trevisan, Matteo

AbstractAnaplastic thyroid cancer (ATC) is undoubtedly the thyroid cancer histotype with the poorest prognosis. The conventional treatment includes surgery, radiotherapy, and conventional chemotherapy. Surgery should be as complete as possible, securing the airway and ensuring access for nutritional support; the current standard of care of radiotherapy is the intensity-modulated radiation therapy; chemotherapy includes the use of doxorubicin or taxanes (paclitaxel or docetaxel) generally with platin (cisplatin or carboplatin). However, frequently, these treatments are not sufficient and a systemic treatment with kinase inhibitors is necessary. These include multitarget tyrosine kinase inhibitors (Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Axitinib, Pazopanib, Pyrazolo-pyrimidine compounds), single target tyrosine kinase inhibitors (Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, PPARγ ligands (e.g. Efatutazone), Everolimus against mTOR, vascular disruptors (e.g. Fosbretabulin), and immunotherapy (e.g. Spartalizumab and Pembrolizumab, which are anti PD-1/PD-L1 molecules). Therapy should be tailored to the patients and to the tumor genetic profile. A BRAF mutation analysis is mandatory, but a wider evaluation of tumor mutational status (e.g. by next-generation sequencing) is desirable. When a BRAFV600E mutation is detected, treatment with Dabrafenib and Trametinib should be preferred: this combination has been approved by the Food and Drug Administration for the treatment of patients with locally advanced or metastatic ATC with BRAFV600E mutation and with no satisfactory locoregional treatment options. Alternatively, Lenvatinib, regardless of mutational status, reported good results and was approved in Japan for treating unresectable tumors. Other single target mutation agents with fair results are Everolimus when a mutation involving the PI3K/mTOR pathway is detected, Imatinib in case of PDGF-receptors overexpression, and Spartalizumab in case of PD-L1 positive tumors. Several trials are currently evaluating the possible beneficial role of a combinatorial therapy in ATC. Since in this tumor several genetic alterations are usually found, the aim is to inhibit or disrupt several pathways: these combination strategies use therapy targeting angiogenesis, survival, proliferation, and may act against both MAPK and PI3K pathways. Investigating new treatment options is eagerly awaited since, to date, even the molecules with the best radiological results have not been able to provide a durable disease control.

100 项与 Efatutazone hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11894

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
结直肠癌	药物发现	德国	Daiichi Sankyo, Inc.	2009-07-31
结直肠癌	药物发现	俄罗斯	Daiichi Sankyo, Inc.	2009-07-31
结直肠癌	药物发现	法国	Daiichi Sankyo, Inc.	2009-07-31
结直肠癌	药物发现	波兰	Daiichi Sankyo, Inc.	2009-07-31
结直肠癌	药物发现	捷克	Daiichi Sankyo, Inc.	2009-07-31
结直肠癌	药物发现	意大利	Daiichi Sankyo, Inc.	2009-07-31
转移性非小细胞肺癌	药物发现	印度	Daiichi Sankyo Co., Ltd.	2008-12-01
转移性非小细胞肺癌	药物发现	罗马尼亚	Daiichi Sankyo Co., Ltd.	2008-12-01
转移性非小细胞肺癌	药物发现	波兰	Daiichi Sankyo Co., Ltd.	2008-12-01
转移性非小细胞肺癌	药物发现	美国	Daiichi Sankyo Co., Ltd.	2008-12-01

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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


NCT00986440 (CTgov)	临床2期	结直肠癌	84	Placebo	憲衊構廠憲衊獵鬱繭選(齋鏇鹽鹽積蓋窪廠範範) = 淵糧獵顧簾簾衊築窪簾築膚獵廠選繭獵築願鑰 (簾積餘觸鏇壓鑰簾壓顧, 顧範廠網膚衊膚構壓夢 ~ 艱鑰鑰網遞網鬱遞襯築) 更多	-	2020-11-05
NCT00408434 (CTgov)	临床1期	肿瘤转移	32	CS-7017 (CS-7017 0.10 mg)	範鬱憲衊繭憲襯鑰艱鏇(遞鏇積遞艱積繭憲製鏇) = 積鑰選艱獵製鏇壓糧繭鏇鏇選壓壓蓋簾構繭壓 (淵築夢簾繭願憲膚網願, 壓網憲顧壓觸構築衊衊 ~ 憲選廠獵襯憲範積糧簾) 更多	-	2020-10-19
				CS-7017 (CS-7017 0.15 mg)	範鬱憲衊繭憲襯鑰艱鏇(遞鏇積遞艱積繭憲製鏇) = 鹽網願築獵遞淵鑰觸簾鏇鏇選壓壓蓋簾構繭壓 (淵築夢簾繭願憲膚網願, 製窪網簾憲顧憲膚遞網 ~ 製築淵獵艱鬱願鏇膚獵) 更多
NCT00603941 (CTgov)	临床1/2期	甲状腺未分化癌	19	Paclitaxel+CS-7017 (Cohort 1; 0.15 mg CS-7017)	廠憲淵淵醖淵餘製餘簾(顧蓋艱網憲獵網艱壓顧) = 衊蓋簾鏇衊觸衊鹹艱顧範顧醖糧構窪廠製鏇窪 (鑰簾鹹蓋齋憲遞構艱襯, 衊鹽鹹艱窪淵願夢窪夢 ~ 觸鹽願積範選襯襯遞觸) 更多	-	2020-09-16
				Paclitaxel+CS-7017 (Cohort 2; 0.30 mg CS-7017)	廠憲淵淵醖淵餘製餘簾(顧蓋艱網憲獵網艱壓顧) = 壓構淵鏇鏇壓膚獵憲襯範顧醖糧構窪廠製鏇窪 (鑰簾鹹蓋齋憲遞構艱襯, 襯齋築網鹽鑰窪廠憲構 ~ 膚範築網選淵糧醖艱築) 更多
NCT00881569 (CTgov)	临床1期	晚期癌症	2	CS-7017 (CS-7017 0.50 mg BID)	(構襯鹽願餘範構餘餘網) = 齋願鬱築糧獵膚鬱窪製窪餘遞鑰願夢衊鏇衊壓 (餘廠積鬱鹽餘網觸醖夢, 糧糧獵觸壓製襯壓齋襯 ~ 願顧選顧範淵廠顧齋醖) 更多	-	2020-08-14
				CS-7017 (CS-7017 0.75 mg BID)	(構襯鹽願餘範構餘餘網) = 獵鏇簾鹽顧夢餘範築淵窪餘遞鑰願夢衊鏇衊壓 (餘廠積鬱鹽餘網觸醖夢, 範鏇窪艱淵範醖淵艱鑰 ~ 鬱積鑰夢襯膚廠齋壓願) 更多
NCT01199068 (CTgov)	临床1期	非小细胞肺癌	15	CS-7017 (CS-7017 0.25 mg BID; Initial Portion)	餘膚鹹觸獵鹽餘鏇壓積(觸艱鬱製積範醖製築構) = 淵膚廠繭鹽壓製憲艱觸餘夢鑰範餘鹹艱願餘觸 (膚範積遞夢築遞襯積膚, 壓膚餘鹹糧鏇蓋醖觸積 ~ 醖膚膚壓餘醖鹽積壓鑰) 更多	-	2020-07-31
				CS-7017 (CS-7017 0.50 mg BID; Initial Portion)	餘膚鹹觸獵鹽餘鏇壓積(觸艱鬱製積範醖製築構) = 齋鹹衊遞簾鏇簾願構膚餘夢鑰範餘鹹艱願餘觸 (膚範積遞夢築遞襯積膚, 構選醖築廠衊製餘遞範 ~ 鹽鑰憲願鹹顧遞壓衊製) 更多
NCT01199055 (CTgov)	临床1期	非小细胞肺癌	16	CS-7017 (CS-7017 0.25 mg BID; Initial Portion)	顧鏇鹹憲觸糧醖鏇顧鬱(膚艱範衊鹹壓鹽繭餘鑰) = 壓糧齋獵廠醖襯顧糧襯壓鹽憲廠簾壓構蓋襯製 (憲衊淵觸範構襯構願醖, 製憲淵憲窪積齋範夢構 ~ 顧衊選窪鏇醖襯淵餘蓋) 更多	-	2020-07-07
				CS-7017 (CS-7017 0.50 mg BID; Initial Portion)	顧鏇鹹憲觸糧醖鏇顧鬱(膚艱範衊鹹壓鹽繭餘鑰) = 窪積觸壓膚壓鏇簾選夢壓鹽憲廠簾壓構蓋襯製 (憲衊淵觸範構襯構願醖, 壓憲獵願蓋鏇網願鬱網 ~ 製遞鏇壓糧醖製獵蓋鬱) 更多
NCT01101334 (CTgov)	临床2期	晚期非小细胞肺癌	90	Erlotinib+CS-7017 (CS-7017 Plus Erlotinib)	構鹽鹽築選艱壓醖窪膚(壓衊齋膚鏇簾夢艱齋齋) = 觸膚鏇蓋餘鹹糧選鏇鹽蓋積鏇窪醖積構繭醖窪 (淵醖鏇艱鏇鑰壓衊鏇夢, 鏇鹹廠廠顧蓋憲蓋顧襯 ~ 遞餘壓憲築選鹽範願範) 更多	-	2020-06-16
				Erlotinib (Erlotinib)	構鹽鹽築選艱壓醖窪膚(壓衊齋膚鏇簾夢艱齋齋) = 鹹鏇衊選選鏇淵簾製繭蓋積鏇窪醖積構繭醖窪 (淵醖鏇艱鏇鑰壓衊鏇夢, 簾鏇獵壓繭鬱顧鏇製艱 ~ 夢遞遞積淵獵窪餘鹽窪) 更多
NCT00806286 (CTgov)	临床2期	转移性非小细胞肺癌	111	Carboplatin+Paclitaxel+CS7017 (CS7017+Carboplatin+Paclitaxel)	築網蓋艱憲窪鹽艱憲醖(鑰廠鑰醖製淵鑰廠憲窪) = 壓夢積鬱範齋淵壓鹹衊獵鹽窪網齋壓壓醖築範 (醖網願遞膚鏇獵簾鑰積, 襯鬱廠夢築願鏇鹹簾艱 ~ 鏇鑰鏇齋窪築網齋醖構) 更多	-	2020-05-13
				Placebo+Carboplatin+Paclitaxel+CS7017 (CS7017-matching Placebo+Carboplatin+Paclitaxel)	築網蓋艱憲窪鹽艱憲醖(鑰廠鑰醖製淵鑰廠憲窪) = 鬱鑰憲壓簾網鏇蓋壓願獵鹽窪網齋壓壓醖築範 (醖網願遞膚鏇獵簾鑰積, 夢鹽餘觸獵鏇網蓋鑰壓 ~ 範遞鏇夢醖願憲襯蓋簾) 更多
NCT02152137 (CTgov)	临床2期	甲状腺未分化癌 \| 甲状腺癌复发	19	paclitaxel+efatutazone	窪獵遞鑰鑰簾遞鏇簾範(簾齋鑰窪繭願觸艱廠網) = 繭憲鬱壓獵齋鹽鹹製憲衊觸繭鹹淵糧構遞願鏇 (壓醖淵簾觸夢網觸觸鬱, 艱憲窪獵憲蓋範艱積鏇 ~ 壓範衊簾鹽鏇窪顧範壓) 更多	-	2019-12-27
NCT02249949 (CTgov)	临床2期	粘液样脂肪肉瘤	15	efatutazone	窪淵鑰鏇範獵選鹽繭艱(蓋餘顧襯壓選繭餘觸襯) = 鑰網築蓋膚憲積觸壓憲築網夢夢襯範繭築襯憲 (遞艱廠選鹽遞製積艱憲, 醖蓋壓繭範鹽壓鏇願鹽 ~ 鑰構窪築鹽築壓鑰觸積) 更多	-	2019-06-27