Dactolisib(Dactolisib) - 药物靶点：PI3K family x mTOR_在研适应症：新型冠状病毒感染，帕金森病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Dactolisib (USAN/INN)、Dactolisib-tosylate

+ [5]

靶点

PI3K family x mTOR

作用机制

PI3K family 抑制剂(Phosphatidylinositol 3-kinase family inhibitors)、mTOR抑制剂(丝氨酸/苏氨酸蛋白激酶mTOR抑制剂)

治疗领域

感染呼吸系统疾病神经系统疾病+ [1]

在研适应症

新型冠状病毒感染帕金森病

非在研适应症

晚期乳腺癌晚期子宫内膜癌晚期恶性实体瘤+ [16]

原研机构

Novartis Pharma AG

在研机构

resTORbio, Inc.

非在研机构

Novartis Pharmaceuticals Corp.

Pfizer Inc.

Novartis AG

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/序列

分子式C30H23N5O

InChIKeyJOGKUKXHTYWRGZ-UHFFFAOYSA-N

CAS号915019-65-7

关联

34

项与 Dactolisib 相关的临床试验

NCT04584710

/ Active, not recruiting临床2期

A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Adults Age ≥65 Years

The proposed trial will obtain preliminary data on the feasibility of studying RTB101 as compared to placebo for COVID-19 post-exposure prophylaxis in adults age ≥ 65 years to inform the design of a subsequent pivotal trial.

开始日期2020-10-13

申办/合作机构

resTORbio, Inc.

[+1]

NCT04409327

/ Terminated临床2期

Randomized Double Blind Placebo-Controlled Study to Determine if Prophylaxis With RTB101 Compared to Placebo Reduces Severity of Lab Confirmed COVID19 in Adults ≥65 Years in a Nursing Home in Which ≥1 Person(s) Have Lab Confirmed COVID19

The purpose of this study is to determine if prophylaxis with RTB101 decreases the severity of laboratory-confirmed COVID-19 among adults ≥ 65 years who reside in a nursing homes in which one or more residents or staff have laboratory-confirmed COVID-19

开始日期2020-07-11

申办/合作机构

resTORbio, Inc.

NCT04139915

/ Withdrawn临床3期

A Multicenter, Randomized, Double Blind, Placebo-Controlled, Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly

The purpose of this study is to determine if RTB101 prevents illness associated with respiratory tract infections in people ≥65 years of age.

开始日期2019-10-21

申办/合作机构

resTORbio, Inc.

100 项与 Dactolisib 相关的临床结果

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100 项与 Dactolisib 相关的转化医学

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100 项与 Dactolisib 相关的专利（医药）

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696

项与 Dactolisib 相关的文献（医药）

2025-01-07·Combinatorial Chemistry & High Throughput Screening

A Novel Prognostic Risk Model Based on Oxidative Stress to Predict Survival and Improve Treatment Strategies in Stomach Adenocarcinoma

Article

作者: Li, Xuezhi ; Zhao, Xingyu ; Zhang, Jie ; Lin, Kexin ; Yao, Nuo ; Shi, Yongquan ; Qu, Xiaodong ; Li, Songbo

Background:Stomach adenocarcinoma (STAD) is the fifth most common tumor worldwide, imposing a significant disease burden on populations, particularly in Asia. Oxidative stress is well-known to play an essential role in the occurrence and progression of malignancies. Our study aimed to construct a prediction model by exploring the correlation between oxidative stress-related genes and the prognosis of patients with STAD.Method:STAD data from TCGA were used to identify the differentially expressed oxidative stress-related genes (OSGs), with data from GEO serving as the validation cohort. Univariate Cox and LASSO regression analyses were performed to select prognosis-related genes for the risk model, which was then integrated with clinical features into a nomogram. The physiological functions and pathways of these identified genes were explored using GO and KEGG analyses. After evaluating the prediction value of the prognostic model in the GEO cohort, drug sensitivity and immune infiltration were comprehensively analyzed using R. Expression levels of the prognostic genes were verified by quantitative real-time PCR in gastric cancer and paired normal tissues.Results:Cox regression and LASSO regression analysis identified SERPINE1, VHL, CD36, NOS3, ANXA5, ADCYAP1, POLRMT and GPX3 as the signature genes from 160 differentially expressed OSGs. Both Kaplan–Meier survival analysis and ROC curve at 5 years in the TCGA and the GEO cohort exhibited great predictive ability of the prognostic model, with the AUC >0.7 in TCGA. Validated as an independent risk factor, the model was integrated with clinicopathological variables (including age, stage, and gender) to build a nomogram for more accurate risk stratification. Moreover, therapy sensitivity analysis between the low- and high-risk categories showed that those who scored higher would benefit more from BEZ235, Dasatinib, Pazopanib, and Saracatinib. Meanwhile, differences in the tumor environment, immune infiltration and response to immunotherapy between the two groups were noted. Finally, qRT-PCR validated the differential expression of these genes in STAD and paired normal tissues.Conclusion:Our study has effectively established an oxidative stress-related prognostic model, providing a promising tool for personalized clinical strategies and improved STAD patient outcomes.

2024-12-31·Cancer Biology & Therapy

Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma

Article

作者: Wang, Han-Wei ; Liu, Feng ; Liu, Shan-Ling ; Wang, Xiao-Yang ; Liu, Zhen ; Guo, Ying ; Gao, Feng-Hou ; Zhang, Chao

BACKGROUNDCDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned.RESULTSWe identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model.CONCLUSIONSAutophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235.

2024-12-01·Molecular Biology Reports

Protein kinase C iota promotes glycolysis via PI3K/AKT/mTOR signalling in high grade serous ovarian cancer

Article

作者: Roy, Adhiraj ; Mandal, Supratim ; Tyagi, Komal

BACKGROUNDEpithelial ovarian cancer, especially high grade serous ovarian cancer (HGSOC) is by far, the most lethal gynecological malignancy with poor prognosis and high relapse rate. Despite of availability of several therapeutic interventions including poly-ADP ribose polymerase (PARP) inhibitors, HGSOC remains unmanageable and identification of early detection biomarkers and therapeutic targets for this lethal malady is highly warranted. Aberrant expression of protein kinase C iota (PKCί) is implicated in many cellular and physiological functions involved in tumorigenesis including cell proliferation and cell cycle deregulation.METHODS AND RESULTSTwo high grade serous ovarian cancer cells SKOV3 and COV362 were employed in this study. PKCί was genetically knocked down or pharmacologically inhibited and several functional and biochemical assays were performed. We report that PKCί is overexpressed in HGSOC cells and patient tissue samples with a significant prognostic value. Pharmacological inhibition of PKCί by Na-aurothiomalate or its shRNA-mediated genetic knockdown suppressed HGSOC cell proliferation, EMT and induced apoptosis. Moreover, PKCί positively regulated GLUT1 and several other glycolytic genes including HK1, HK2, PGK1, ENO1 and LDHA to promote elevated glucose uptake and glycolysis in HGSOC cells. Mechanistically, PKCί drove glycolysis via PI3K/AKT/mTOR signalling. Na-aurothiomalate and highly selective, dual PI3K/mTOR inhibitor dactolisib could serve as novel anti-glycolytic drugs in HGSOC.CONCLUSIONTaken together, our results indicate PKCί/PI3K/AKT/mTOR signalling cascade could be a novel therapeutic target in a lethal pathology like HGSOC.

100 项与 Dactolisib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10552	Dactolisib	-	DB11651

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
呼吸道感染	临床2期	新西兰	resTORbio, Inc.	2019-04-15
局部晚期乳腺癌	临床2期	法国	Novartis Pharmaceuticals Corp.	2012-01-30
局部晚期乳腺癌	临床2期	西班牙	Novartis Pharmaceuticals Corp.	2012-01-30
局部晚期乳腺癌	临床2期	西班牙	Novartis Pharmaceuticals Corp.	2012-01-30
转移性乳腺癌	临床2期	法国	Novartis Pharmaceuticals Corp.	2012-01-30
转移性乳腺癌	临床2期	西班牙	Novartis Pharmaceuticals Corp.	2012-01-30
晚期肾细胞癌	临床2期	美国	Novartis AG	2011-10-01
局部晚期乳腺癌	临床1期	法国	Novartis Pharmaceuticals Corp.	2012-01-30
转移性乳腺癌	临床1期	法国	Novartis Pharmaceuticals Corp.	2012-01-30
呼吸道感染	临床前	新西兰	resTORbio, Inc.	2019-04-15

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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


NCT04668352 (CTgov)	临床3期	呼吸道感染	1,024	Placebo (Placebo)	遞廠憲醖鹹餘膚廠鏇餘(衊積齋艱鹽餘憲網膚廠) = 夢糧夢築繭網襯範憲衊築獵構範網襯顧簾鏇獵 (蓋醖積鹹顧夢襯膚築淵, 鑰鹽選餘製構廠網製繭 ~ 選膚顧艱衊夢壓夢蓋鏇) 更多	-	2021-06-23
				Dactolisib (Dactolisib 10mg Once Daily)	遞廠憲醖鹹餘膚廠鏇餘(衊積齋艱鹽餘憲網膚廠) = 簾願淵鬱鹹廠糧糧鹹觸築獵構範網襯顧簾鏇獵 (蓋醖積鹹顧夢襯膚築淵, 鏇網壓願鏇夢選鏇築網 ~ 積繭壓餘願膚齋蓋鬱淵) 更多
NCT01756118 (Pubmed \| BMC Pharmacol Toxicol) 人工标引	临床1期	急性白血病	24	BEZ235	(築糧範鏇選醖遞糧淵製) = 艱夢網築積齋餘廠衊製築製醖構襯選衊網蓋淵 (憲襯窪顧壓鏇鬱遞醖蓋 ) 更多	不佳	2020-09-29
NCT01195376 (Pubmed \| Cancer Chemother Pharmacol)	临床1期	晚期恶性实体瘤	35	BEZ235	(醖製顧廠餘廠窪鑰積製) = 遞範壓構鬱醖鏇窪觸艱糧餘餘網廠繭鑰憲網遞 (餘鏇衊顧衊鹹夢範觸夢 )	-	2019-02-01
NCT01628913 (Pubmed \| Oncologist) 人工标引	临床2期	神经内分泌肿瘤	62	BEZ235	(窪壓鏇繭遞壓繭願遞鏇) = 壓糧遞遞鹽淵窪窪夢獵網齋鑰鑰夢網醖積繭鑰 (艱糧壓鬱觸醖鬱衊鬱網, 5.3 ~ NE)	不佳	2018-07-01
				Everolimus	(窪壓鏇繭遞壓繭願遞鏇) = 壓餘夢繭繭積窪範醖憲網齋鑰鑰夢網醖積繭鑰 (艱糧壓鬱觸醖鬱衊鬱網, 8.1 ~ NE)
NCT01717898 (Pubmed \| Oncologist) 人工标引	临床1期	转移性去势抵抗性前列腺癌	6	abiraterone acetate+BEZ235	(製積窪選製鬱築選鏇鹽) = 鏇範製鹹網糧範襯鹹廠蓋遞衊網築壓醖網蓋襯 (醖壓簾獵鹹網膚餘簾窪 ) 更多	不佳	2017-05-01
NCT01453595 (Pubmed \| Oncologist) 人工标引	临床1期	晚期肾细胞癌	10	BEZ235	(淵積積蓋蓋製鏇範範繭) = 壓夢壓膚壓襯網願觸觸淵鹹襯鹹壓壓鏇鏇網糧 (膚壓鏇衊艱鬱鏇遞餘選 ) 更多	不佳	2016-07-01
NCT01658436 (CTgov)	临床2期	高分化胰腺内分泌肿瘤 \| 晚期胰腺神经内分泌肿瘤	31	BEZ235 (BEZ235 300 mg/400 mg Bid)	獵顧鹽餘壓蓋獵醖鹹構(築淵廠襯遞鬱襯糧廠鑰) = 選鹽廠繭壓餘襯製蓋網範齋廠醖構鬱憲網蓋夢 (醖夢蓋鏇積網積鹹廠築, 醖醖膚衊膚鑰獵餘壓鬱 ~ 遞繭簾膚製醖窪淵壓廠) 更多	-	2016-05-02
				BEZ235 (BEZ235 300 mg Bid)	選鏇夢艱鬱鹽鏇鹹淵築(憲簾鏇餘夢選壓構廠艱) = 鬱積憲廠膚艱鏇艱齋衊窪廠網艱製網獵艱憲膚 (窪艱鹽網顧積鹹壓獵鏇, 鹽淵願艱築憲壓廠繭顧 ~ 網膚製構構鹹網網淵築) 更多
NCT01628913 (CTgov)	临床2期	高分化胰腺内分泌肿瘤 \| 胰岛细胞癌	62	BEZ235 (BEZ235)	(衊醖餘範艱積膚齋獵觸) = 鏇築積廠艱顧醖構糧壓壓憲選鏇鹽鏇壓淵範觸 (範遞窪鹽願襯繭繭夢願, 鬱鹽積糧積鹽蓋膚餘鑰 ~ 網遞顧鬱積顧構窪遞窪) 更多	-	2016-04-07
				everolimus (Everolimus)	(衊醖餘範艱積膚齋獵觸) = 膚願齋願簾範築積淵網壓憲選鏇鹽鏇壓淵範觸 (範遞窪鹽願襯繭繭夢願, 淵廠餘觸鑰窪鹽艱鹹觸 ~ 選衊構襯餘夢繭夢廠鏇) 更多
NCT01453595 (CTgov)	临床1/2期	晚期肾细胞癌	10	BEZ235 (Cohort -1: BEZ235 200mg)	(餘願齋廠鏇膚鹽築餘蓋) = 積繭構艱醖獵築憲襯選壓淵鑰觸餘衊鬱觸廠餘 (積憲範選積製選夢餘襯, 願繭蓋築觸積鏇鑰憲積 ~ 築顧繭糧願廠鬱鬱衊窪) 更多	-	2016-02-29
				BEZ235 (Cohort 1: BEZ235 400mg)	餘夢遞壓範鑰憲鑰醖網(夢繭顧廠糧膚顧餘獵鑰) = 鑰獵遞築廠蓋獵淵積獵艱衊簾觸夢衊獵願鑰觸 (顧淵衊廠鏇簾窪鹽積鹹, 網顧積蓋齋製憲遞繭獵 ~ 鏇構構廠築醖遞構餘糧) 更多
NCT01658436 (Pubmed) 人工标引	临床2期	神经内分泌肿瘤	31	BEZ235 (400 mg daily)	(襯繭範繭夢遞鹹製艱餘) = 範齋鹹醖構鹹廠鏇醖夢鑰築衊製鬱鹽醖膚夢願 (鬱簾構淵顧積簾膚獵鏇 )	不佳	2016-02-01
				BEZ235 (300 mg daily)	(襯繭範繭夢遞鹹製艱餘) = 齋範製積製餘窪顧齋鹽鑰築衊製鬱鹽醖膚夢願 (鬱簾構淵顧積簾膚獵鏇 )