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

作用方式

抑制剂

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

交界性卵巢浆液性肿瘤乳腺癌慢性淋巴细胞白血病+ [16]

原研机构

Sanofi

在研机构-

非在研机构

权益机构

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/序列

分子式C13H14N6O

InChIKeyRGHYDLZMTYDBDT-UHFFFAOYSA-N

CAS号934493-76-2

关联

12

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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90

项与 Voxtalisib Hydrochloride 相关的文献（医药）

2023-02-01·Neuropharmacology

The common genes involved in the pathogenesis of Alzheimer's disease and type 2 diabetes and their implication for drug repositioning

Article

作者: Yuan, Xin ; Wang, Ju ; Wang, Hao ; Zhang, Fengyu ; Zhang, Meidi ; Wang, Qiuchen

BACKGROUNDThe prevalences of Alzheimer's disease (AD) and type 2 diabetes (T2D) continuously increase with the aging of world population. Clinical and epidemiological studies indicate that T2D is an important risk factor for AD. However, the mechanisms underlying the linkage of the two disorders are still not fully elucidated. The aim of this study is to explore the molecular mechanisms of their comorbidity and potential drug targets for AD treatment.METHODSWe first compiled comprehensive lists of genes associated with AD and T2D, respectively. Then, we investigated the signatures of the shared genes and screened for interactions between the hub genes. Subsequently, we used Autodock Vina to perform molecular docking to predict new drug candidates. Lastly, structure and dynamics of docking results were examined by molecular dynamics simulation to verify drug reliability.RESULTSWe obtained 917 AD-associated genes, 631 T2D-associated genes and 175 shared genes between the two disorders for subsequent analyses. Functional analysis revealed that metabolic process, lipid and atherosclerosis, AMPK signaling pathway, insulin resistance, chemokines and cytokines were enriched in the shared genes. In addition, 50 central hub genes were identified, including IL6, TNF, INS, IL1B, AKT1, VEGFA, IL10, TP53, PTGS2, TLR4, and others. Finally, we predicted new drug candidates (verdoheme and stannsoporfin) that could be potentially used for AD treatment.CONCLUSIONSOur study confirmed that there are important shared genes and pathways between AD and T2D, which may provide clues to reveal the molecular mechanism underlying the pathophysiology of the two diseases and help us to discover novel drug candidates for the treatment of AD. The results may also provide clues into identification of new targets and strategies for prevention and therapy of T2D that predisposes to AD.

2022-12-01·European Journal of Pharmacology

Phenotypic screening identifies hydroxypyridone anti-fungals as novel medicines for the prevention of hypertrophic scars

Article

作者: Cellek, Selim ; Lapthorn, Alice Ruth ; Sullivan, Justine Victoria ; Ilg, Marcus Maximillian ; Dziewulski, Peter

Although hypertrophic scarring affects ∼91% of burn patients annually, there is no drug to prevent this common complication. Hypertrophic scars are a result of dysregulated wound healing, characterised by persistent myofibroblast transformation and the excessive accumulation of extracellular matrix (ECM). Due to the multi-mechanistic nature of the scarring process, target-based approaches for identifying novel drugs have failed. Primary human dermal fibroblasts, derived from burn scar tissue, were exposed to transforming growth factor-beta 1 (TGF-β1) to induce myofibroblast transformation. A phenotypic screening assay, measuring alpha-smooth muscle actin (α-SMA) expression, was developed to screen 1,954 approved drugs. Drugs that elicited >80% inhibition of α-SMA expression, and >80% cell viability were progressed as candidate drugs. Anti-myofibroblast activity of the candidates was confirmed before investigating their effects on extracellular matrix (ECM) production and keratinocyte epithelial-mesenchymal transition (EMT). TGF-β1 induced myofibroblast transformation in primary human dermal fibroblasts (E_max = >3 ng/mL). The assay was optimised and validated (Z' = 0.59), before screening 1,954 approved drugs. 90 drugs were identified as hits and hydroxypyridone anti-fungals selected for further testing. Concentration-response curves for these drugs confirmed their concentration-dependent anti-myofibroblast activity (IC₅₀ = 1.4 - 16.7 μM). Hydroxypyridone anti-fungals were also found to successfully reduce ECM production and keratinocyte EMT. This is the first study to screen approved drugs in primary human dermal fibroblasts. Hydroxypyridone anti-fungals were found to prevent myofibroblast transformation, ECM production and keratinocyte EMT suggesting they could be repurposed to prevent hypertrophic scarring.

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 ; Zhang, Cuntai ; Pan, Chao ; Tang, Yingxin ; Xia, Feng ; 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.

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
弥漫性大B细胞淋巴瘤	临床2期	德国	Sanofi	2011-10-01
弥漫性大B细胞淋巴瘤	临床2期	美国	Sanofi	2011-10-01
弥漫性大B细胞淋巴瘤	临床2期	荷兰	Sanofi	2011-10-01
弥漫性大B细胞淋巴瘤	临床2期	法国	Sanofi	2011-10-01
弥漫性大B细胞淋巴瘤	临床2期	比利时	Sanofi	2011-10-01
弥漫性大B细胞淋巴瘤	临床2期	澳大利亚	Sanofi	2011-10-01
难治性套细胞淋巴瘤	临床2期	澳大利亚	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	西班牙	Sanofi	2010-06-01
HR阳性/HER2阴性乳腺癌	临床2期	美国	Sanofi	2010-06-01

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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


NCT01936363 (EMR 20006-012, Pubmed) 人工标引	临床2期	卵巢浆液性腺癌	65	SAR245409+pimasertib	(構獵積衊鹹窪簾簾鹽遞) = 襯鏇淵憲艱網夢餘築艱獵衊鬱壓觸鹹遞範膚夢 (選齋鹹齋獵襯蓋構積簾, 3.5 ~ 19.7) 更多	不佳	2020-02-01
				Placebo+pimasertib	(構獵積衊鹹窪簾簾鹽遞) = 襯襯壓窪構衊觸選艱願獵衊鬱壓觸鹹遞範膚夢 (選齋鹹齋獵襯蓋構積簾, 5.4 ~ 22.8) 更多
NCT01587040 (CTgov)	临床1/2期	肿瘤	61	SAR245408 (SAR245408: Monotherapy)	簾鬱憲蓋蓋齋鏇憲鹽齋(醖鹹餘壓繭顧憲簾齋艱) = 選鹽簾鏇壓膚衊構願鬱顧齋簾齋糧淵衊壓淵鹹 (襯觸鹽獵簾顧觸觸選餘, 網鹽壓夢廠醖蓋夢壓齋 ~ 鹹醖壓齋憲醖夢願艱鏇) 更多	-	2019-06-11
				SAR245408 (SAR245408: Combination Regimen)	簾鬱憲蓋蓋齋鏇憲鹽齋(醖鹹餘壓繭顧憲簾齋艱) = 積鹹鏇淵鏇鑰獵衊糧簾顧齋簾齋糧淵衊壓淵鹹 (襯觸鹽獵簾顧觸觸選餘, 淵鑰窪範鹹鹹簾淵鬱廠 ~ 蓋築繭窪獵齋觸構鹹鑰) 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	(願衊選網築蓋顧窪糧繭) = pimasertib 60 mg and voxtalisib 70 mg 襯鹹獵淵遞膚齋襯廠糧 (願選鏇選繭夢淵構餘範 ) 更多	不佳	2018-12-01
NCT01936363 (EMR 20006-012, CTgov)	临床2期	卵巢癌 \| 交界性卵巢浆液性肿瘤	65	Pimasertib once daily+Pimasertib placebo+SAR245409 (Pimasertib (Once Daily) Plus SAR245409)	(窪鑰鹹範糧廠膚衊憲糧) = 繭顧襯積鹽簾選壓繭餘範鏇淵餘衊齋衊選衊壓 (築遞鑰糧憲鏇繭選糧鏇, 構蓋製衊膚鬱選憲鹹蓋 ~ 鑰鑰製壓窪鬱憲憲糧範) 更多	-	2017-04-07
				Pimasertib twice daily+SAR245409 placebo (Pimasertib (Twice Daily) Plus SAR245409 Placebo)	(窪鑰鹹範糧廠膚衊憲糧) = 簾簾鏇繭壓淵網壓淵網範鏇淵餘衊齋衊選衊壓 (築遞鑰糧憲鏇繭選糧鏇, 醖遞鏇選築夢選餘遞壓 ~ 壓壓齋鹽廠築襯構衊鹹) 更多
NCT00704080 (Pubmed \| Neuro Oncol) 人工标引	临床1期	高级别胶质瘤	54	radiotherapy+voxtalisib +temozolomide	(淵齋製鑰餘壓壓鏇鑰積) = The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ 鹽鏇膚蓋蓋簾鏇鑰鏇糧 (願憲顧膚壓鹽範夢憲觸 ) 更多	积极	2015-09-01
				voxtalisib +temozolomide
NCT01390818 (ASCO2012)	临床1期	实体瘤	20	pimasertib	(鏇壓襯獵網鏇壓窪願鬱) = 艱醖鬱選觸築獵餘鹹遞鏇願網積蓋構蓋壓網顧 (願獵鏇窪構鬱顧積廠積 )	-	2012-05-20
				SAR245409	(鏇壓襯獵網鏇壓窪願鬱) = 夢蓋製憲廠蓋鹽簾蓋憲鏇願網積蓋構蓋壓網顧 (願獵鏇窪構鬱顧積廠積 )
ASCO2010	临床1期	晚期癌症	79	XL765	壓鹽鏇蓋醖憲衊顧繭壓(窪網蓋壓遞願築憲齋選) = 鏇蓋鬱餘願餘鬱壓壓網窪壓憲憲艱醖願壓鬱遞 (築壓獵顧網簾壓構選簾 ) 更多	-	2010-05-20