Voxtalisib Hydrochloride(Voxtalisib Hydrochloride) - 药物靶点：PI3Kα x mTORC1 x mTORC2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Voxtalisib

靶点

PI3Kα x mTORC1 x mTORC2

作用机制

PI3Kα抑制剂(磷脂酰肌醇3-激酶α抑制剂)、mTORC1抑制剂(哺乳动物雷帕霉素靶蛋白(mTORC1)复合体抑制剂)、mTORC2抑制剂(mTOR复合物-2抑制剂)

治疗领域

肿瘤免疫系统疾病内分泌与代谢疾病+ [7]

在研适应症-

非在研适应症

乳腺癌慢性淋巴细胞白血病结直肠癌+ [13]

原研机构

Sanofi

在研机构-

非在研机构

EMD Serono, Inc.

Sanofi

Exelixis, Inc.

最高研发阶段终止临床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C13H14N6O

InChIKeyRGHYDLZMTYDBDT-UHFFFAOYSA-N

CAS号934493-76-2

关联

13

项与 Voxtalisib Hydrochloride 相关的临床试验

NCT01936363 / Completed临床2期

Phase II Randomized Double Blind Placebo Controlled Trial of Combination of Pimasertib With SAR245409 or of Pimasertib With SAR245409 Placebo in Subjects With Previously Treated Unresectable Low Grade Ovarian Cancer

This is a double blind, randomized, placebo-controlled, 2-arm, Phase 2 trial investigating the efficacy and safety of combination therapy of pimasertib plus SAR245409 and pimasertib placebo administered once per day compared to pimasertib administered twice per day plus SAR245409 placebo administered once per day in participants with previously treated unresectable low-grade serous ovarian or peritoneal carcinoma or serous borderline ovarian or peritoneal tumors.

开始日期2013-09-30

申办/合作机构

EMD Serono, Inc.

[+1]

NCT01587040 / Completed临床1/2期

International, Multicenter, Open-label, Treatment-extension Study for Subjects Who Completed a Phase 1 or Phase 2 Parental Study to Continue Receiving Treatment With SAR245408 or SAR245409 as a Monotherapy or as a Combination Regimen

Primary Objective:
The purpose of this study was to determine the long term safety and tolerability of SAR245408 and SAR245409 as a monotherapy or as part of a combination regimen in participants who were benefiting from treatment.

开始日期2012-07-20

申办/合作机构

Sanofi

NCT01596270 / Completed临床1期

A Phase 1 Dose-escalation Study of the Safety and Pharmacokinetics of a Tablet Formulation of SAR245409 Administered Daily to Patients With Solid Tumors or Lymphoma

Primary Objective:
- To evaluate the safety and tolerability of SAR245409 tablets administered once or twice a day in patients with solid tumors or lymphoma.
Secondary Objectives:
To evaluate blood levels of SAR245409 after administration of SAR245409 tablets once or twice a day in patients with solid tumors or lymphoma.
To evaluate the effect of food on blood levels of SAR245409 after administration of SAR245409 tablets in patients with solid tumors or lymphoma.
To evaluate the effect of SAR245409 on the body after administration of SAR245409 tablets once or twice a day in patients with solid tumors or lymphoma.
To obtain information on how SAR245409 administered once or twice a day to patients with solid tumors or lymphoma affect disease symptoms and study treatment side effects as reported by the patients on a questionnaire.
To explore the antitumor activity of SAR245409 tablets administered once or twice a day to patients with solid tumors or lymphoma.

开始日期2012-06-01

申办/合作机构

Sanofi

100 项与 Voxtalisib Hydrochloride 相关的临床结果

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100 项与 Voxtalisib Hydrochloride 相关的转化医学

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100 项与 Voxtalisib Hydrochloride 相关的专利（医药）

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44

项与 Voxtalisib Hydrochloride 相关的文献（医药）

2022-11-01·iScience

Integrative genomic analysis facilitates precision strategies for glioblastoma treatment

Article

作者: Zhang, Ping ; Yang, Chen ; Liu, Zhicheng ; Li, Yan ; Wang, Jingxuan ; Chen, Danyang ; Wu, Zhuojin ; Nie, Hao ; Liu, Na ; Tang, Zhouping ; Pan, Chao ; Zhang, Cuntai ; Xia, Feng ; Tang, Yingxin ; Li, Gaigai

Glioblastoma (GBM) is the most common form of malignant primary brain tumor with a dismal prognosis. Currently, the standard treatments for GBM rarely achieve satisfactory results, which means that current treatments are not individualized and precise enough. In this study, a multiomics-based GBM classification was established and three subclasses (GPA, GPB, and GPC) were identified, which have different molecular features both in bulk samples and at single-cell resolution. A robust GBM poor prognostic signature (GPS) score model was then developed using machine learning method, manifesting an excellent ability to predict the survival of GBM. NVP-BEZ235, GDC-0980, dasatinib and XL765 were ultimately identified to have subclass-specific efficacy targeting patients with a high risk of poor prognosis. Furthermore, the GBM classification and GPS score model could be considered as potential biomarkers for immunotherapy response. In summary, an integrative genomic analysis was conducted to advance individual-based therapies in GBM.

2022-11-01·Pathology - Research and Practice

Voxtalisib and low intensity pulsed ultrasound combinatorial effect on glioblastoma multiforme cancer stem cells via PI3K/AKT/mTOR

Article

作者: Uysal, Ayşegül ; Tutak, Irmak ; Ozdil, Berrin

BACKGROUNDGlioblastoma (GBM) is the most aggressive brain tumor contributed to tumor growth by cancer stem cells (CSCs). Targeting CSCs is vital to preventing differentiation into cancer cells, their proliferation, and treatment resistance. According to research, PI3K/AKT/mTOR signaling is active in GBM and GBMCSCs. Anticancer medications combined with ultrasound application have been proposed as a strategy to increase the drug intake of cancer cells. This study aims to investigate the effects of inhibition of PI3K/ AKT/ mTOR pathway with dual inhibitor Voxtalisib (Vox; also known as XL765) and low intensity pulsed ultrasound (LIPUS) combinations in GBM and GBMCSCs in the point of cell survival. F-actin was also used to evaluate cell motility.MATERIALS AND METHODSGBMCSCs were isolated from the human glioblastoma U87 MG cell line using the fluorescence-activated cell sorting (FACS) method. Cells were exposed to various concentrations of Vox, LIPUS, and their combinations. Cell count and viability assay was used to determine drug delivery doses. F-actin and mTOR immunofluorescence staining were used to identify cytoskeletal alterations and PI3K/AKT/mTOR signal pathway suppression, respectively. Additionally, the migration capacity of cells was shown with standard wound-healing experiments.RESULTSHigh doses of Vox+LIPUS inhibited mTOR and decreased the viability in both cell groups. Inhibiting mTOR activated autophagy, and LIPUS increased autophagy in GBM cells. However, GBMCSCs were resistant to autophagy even at high drug dosages. Both in GBM and GBMCSCs, combinations of Vox and LIPUS were observed to decrease F-actin density and cell motility.CONCLUSIONSThe combination of Vox+LIPUS has increased drug effectiveness in targeted GBM and GBMCSCs. Combinatory treatment with PI3K/AKT/mTOR signaling pathway and LIPUS has been thought to help develop more effective therapeutic approaches for GBM.

2022-06-17·Evidence-Based Complementary and Alternative Medicine

β-Carotene Attenuates Apoptosis and Autophagy via PI3K/AKT/mTOR Signaling Pathway in Necrotizing Enterocolitis Model Cells IEC-6

Article

作者: Peng, Kun ; Zhou, Chonggao ; Xu, Guang ; Li, Bixiang ; Ma, Tidong ; Zhao, Fan

Background. Necrotizing enterocolitis (NEC) is a devastating disease affecting the gastrointestinal tract in the newborn period. In recent years, the role of apoptosis and autophagy in intestinal mucosal barrier dysfunction has come into prominence in research regarding the pathogenesis of NEC. β-Carotene is a well-known vitamin A precursor, and its content in breast milk is relatively high, especially in the colostrum. In the present study, we investigated the protective effect of β-carotene on necrotizing enterocolitis model cells IEC-6 induced by lipopolysaccharide (LPS). Methods. CCK-8 assay was performed to evaluate cell viability. The Annexin V-FITC/PI method was used to detect apoptosis. Western blotting was utilized to measure the expression levels of proteins. Immunofluorescence analysis was used to assess the autophagy of IEC-6 cells. Results. Our findings indicated that β-carotene inhibited the apoptosis of IEC-6 cells by downregulating cleaved caspase-3 levels and Bax levels and upregulating Bcl-2 levels, reducing cell autophagy via downregulating LC3II/I ratio and upregulating p62 levels. In addition, the expression of p-PI3K, p-AKT, and p-mTOR was upregulated after β-carotene treatment. Interestingly, these changes induced by β-carotene were partially reversed by rapamycin and voxtalisib. Conclusion. In conclusion, our findings indicated that β-carotene can attenuate apoptosis and autophagy of IEC-6 cells induced by LPS via activating the PI3K/AKT/mTOR signaling pathway. Therefore, β-carotene may be a promising drug used in the clinical treatment of NEC.

100 项与 Voxtalisib Hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Voxtalisib Hydrochloride	-	DB12400

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
难治性套细胞淋巴瘤	临床2期	德国	Sanofi	2011-10-01
HR阳性/HER2阴性乳腺癌	临床2期	法国	Sanofi	2010-06-01
HR阳性/HER2阴性乳腺癌	临床2期	美国	Sanofi	2010-06-01
HR阳性/HER2阴性乳腺癌	临床2期	西班牙	Sanofi	2010-06-01
乳腺癌	临床2期	美国	Sanofi	-
乳腺癌	临床2期	美国	Sanofi	-
乳腺癌	临床2期	西班牙	Sanofi	-
乳腺癌	临床2期	法国	Sanofi	-
乳腺癌	临床前	西班牙	Sanofi	-
乳腺癌	临床前	法国	Sanofi	-

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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


NCT01936363 (EMR 20006-012, Pubmed) 人工标引	临床2期	卵巢浆液性腺癌	65	SAR245409+pimasertib	(觸餘艱願壓襯選淵膚餘) = 繭淵蓋觸襯繭夢選糧鬱顧簾糧簾憲願鬱積簾觸 (餘鏇簾繭願淵衊憲網顧, 3.5 ~ 19.7) 更多	不佳	2020-02-01
				Placebo+pimasertib	(觸餘艱願壓襯選淵膚餘) = 廠衊糧壓壓壓顧顧觸簾顧簾糧簾憲願鬱積簾觸 (餘鏇簾繭願淵衊憲網顧, 5.4 ~ 22.8) 更多
NCT01587040 (CTgov)	临床1/2期	肿瘤	61	SAR245408 (SAR245408: Monotherapy)	襯選襯鹹獵鹹鹽醖齋壓(觸遞鏇膚繭願餘鬱衊艱) = 製醖淵願簾簾範壓齋夢鹹廠遞遞網襯顧網選醖 (艱憲憲鹽窪夢醖積衊襯, 鹹簾顧淵遞憲鹹夢醖網 ~ 範範襯衊憲願製衊積壓) 更多	-	2019-06-11
				SAR245408 (SAR245408: Combination Regimen)	襯選襯鹹獵鹹鹽醖齋壓(觸遞鏇膚繭願餘鬱衊艱) = 鬱構選餘膚鏇鹽鏇願艱鹹廠遞遞網襯顧網選醖 (艱憲憲鹽窪夢醖積衊襯, 糧醖製網蓋鏇蓋廠鬱繭 ~ 構鬱繭願鬱鹹艱窪衊膚) 更多
NCT01390818 (Pubmed \| Med J Aust) 人工标引	临床1期	晚期恶性实体瘤	146	pimasertib+voxtalisib	(繭築範襯壓餘蓋齋鬱淵) = pimasertib 60 mg and voxtalisib 70 mg 鹽鹹繭淵膚齋繭製鹹鹹 (壓鬱蓋醖壓壓鹹壓艱顧 ) 更多	不佳	2018-12-01
NCT01936363 (EMR 20006-012, CTgov)	临床2期	卵巢癌	65	Pimasertib once daily+Pimasertib placebo+SAR245409 (Pimasertib (Once Daily) Plus SAR245409)	(獵淵衊築顧糧觸網憲願) = 鬱鏇艱製齋壓憲壓衊繭廠憲構壓網獵淵醖簾獵 (糧夢顧鏇廠糧鑰鏇獵繭, 淵餘憲醖鏇遞鏇選顧廠 ~ 鏇鬱淵鏇遞顧餘獵積鑰) 更多	-	2017-04-07
				Pimasertib twice daily+SAR245409 placebo (Pimasertib (Twice Daily) Plus SAR245409 Placebo)	(獵淵衊築顧糧觸網憲願) = 糧選餘鹹築願衊選淵艱廠憲構壓網獵淵醖簾獵 (糧夢顧鏇廠糧鑰鏇獵繭, 網艱襯鹽窪壓艱網構獵 ~ 醖醖獵窪醖築築鹽襯鑰) 更多
NCT00704080 (Pubmed \| Neuro Oncol) 人工标引	临床1期	高级别胶质瘤	54	radiotherapy+voxtalisib +temozolomide	(顧淵製築網齋範製餘積) = The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ 顧餘糧夢獵構範鹹繭夢 (構夢簾糧壓淵鏇窪鹽夢 ) 更多	积极	2015-09-01
				voxtalisib +temozolomide
NCT01390818 (ASCO2012)	临床1期	实体瘤	20	pimasertib	(鹹壓鹽觸遞糧醖襯築鹽) = 製醖蓋範淵膚夢齋獵夢鑰繭願遞醖襯廠築鬱觸 (鏇壓觸糧衊網觸壓製繭 )	-	2012-05-20
				SAR245409	(鹹壓鹽觸遞糧醖襯築鹽) = 衊範製遞遞齋醖觸鏇鹹鑰繭願遞醖襯廠築鬱觸 (鏇壓觸糧衊網觸壓製繭 )
ASCO2010	临床1期	晚期癌症	79	XL765	餘觸齋衊艱網構鬱鹹醖(獵繭廠範築艱鹽艱艱選) = 廠艱鏇簾顧鬱積鹽淵淵簾鏇鹽願壓壓淵鏇壓獵 (願餘製蓋築糧蓋願鹹壓 ) 更多	-	2010-05-20