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更新于：2024-12-24
Dactolisib
更新于：2024-12-24
概要
基本信息
在研机构 |
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
A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Adults Age ≥65 Years
NCT04409327
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
NCT04139915
A Multicenter, Randomized, Double Blind, Placebo-Controlled, Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly
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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654
项与 Dactolisib 相关的文献（医药）2024-12-01INTERNATIONAL IMMUNOPHARMACOLOGY
Protective effects of Gumibao recipe on glucocorticoid-included bone microcirculatory endothelial cell injury and the underlying mechanism
Article
作者: Ji, Wanbo ; Xu, Suliang ; Yu, Pengfei ; Liu, Jintao ; Wang, Zhiqiang ; Jiang, Hong ; Wu, Liming ; Liu, Guanhong ; Li, Xiaochun
OBJECTIVE:
To investigate the protective effects of Gumibao recipe on glucocorticoid-included bone microcirculatory endothelial cell (BMEC) injury, and elucidate the possible underlying mechanism.
METHODS:
BMECs were treated with different concentrations of hydrocortisone at different time points, and the viability as well as migration of BMECs were evaluated; furthermore, the release of LDH, levels of VEGF, PAI-1, t-PA, and the content of NO by BMECs have been evaluated by commercially available kits; moreover, the expressions of eNOS, p-PI3K, p-Akt and p-mTOR in BMECs were examined by WB methods. Next, hydrocortisone treated BMECs were co-treated with Gumibao recipe, and the viability, migration and autophagy of BMECs were evaluated.
RESULTS:
0.2 mg/ml and 0.3 mg/ml hydrocortisone significantly decreased viability and migration ability of BMECs, and also impeded the endothelial function of BMECs by decreasing the levels of VEGF, t-PA, the content of NO, and increasing the level of PAI-1. Gumibao medicated serum markedly increased the viability and migration of BMECs, and also increased the levels of VEGF, t-PA, the content of NO, meanwhile decreased the level of PAI-1 in 0.3 mg/ml hydrocortisone treated BMECs; moreover, glucocorticoids inhibited the autophagy of BMECs, and Gumibao recipe significantly increased the autophagy of BMECs; meanwhile, autophagy inhibitor 3-MA partially blocked the protective effects of Gumibao recipe. Finally, gumibao recipe partially abrogated the inhibitory effects of hydrocortisone on the activation of PI3K/Akt/mTOR singling, and these effects were further counteracted by PI3K and mTOR inhibitor NVP-BEZ235.
CONCLUSIONS:
We reported for the first time the protective effects of Gumibao recipe on glucocorticoid-included BMECs injury, and the possible underlying mechanism may be regulating the autophagy of BMECs via PI3K/AKT/mTOR signaling pathway.
2024-12-01Molecular biotechnology
Inhibition of PI3K/Akt/mTOR Signaling Pathway Suppresses 5-Fluorouracil Resistance in Gastric Cancer
Article
作者: Gao, Ziyu ; Shi, Yaxuan ; Xing, Zhiwei ; Gao, Yanan ; Liu, Caixia
BACKGROUND:
At present, 5-Fluorouracil (5-FU) is a crucial anti-cancer drug and is widely used for the treatment of various carcinomas, including gastric cancer (GC). The resistance of GC cells to 5-FU is still a matter of great concern.
OBJECTIVE:
To illustrate the role of PI3K/Akt/mTOR signaling in regulating the cell cycle progression and migration of 5-FU-resistant GC cells.
MATERIAL AND METHODS:
After the establishment of drug-resistant GC cell lines, the effects of 5-FU and/or BEZ235 (the dual inhibitor of PI3K and mTOR) on the activity of parental or drug-resistant GC cells were explored. The viability and localization of GC cells (MKN-45 and MKN-74) and their drug-resistant cells (MKN-45/R and MKN-74/R) were assessed using MTT assays and immunofluorescence staining. The impacts of 5-FU and/or BEZ235 on GC cell cycle progression and cell migration were assessed via flow cytometry analyses and wound healing assays, respectively. GC tissues were collected from patients with GC sensitive or refractory to 5-FU chemotherapy. RT-qPCR and western blot were conducted to measure PI3K, AKT, and mTOR levels in GC cells or tissues.
RESULTS:
After 5-FU treatment, GC cells displayed 5-FU resistance and the viability of drug-resistant cells (MKN-45/R and MKN-74/R) was higher than that of parental cells (MKN-45 and MKN-74). The IC50 values for MKN-45 and MKN-45/R were 8.93 ug/ml and 140 ug/ml, and the values for MKN-74 and MKN-74/R were 3.93 ug/ml and 114.29 ug/ml. Additionally, the PI3K/Akt/mTOR signaling pathway was activated in drug-resistant GC cells and tumor tissues of patients refractory to 5-FU chemotherapy, as evidenced by high PI3K, Akt, and mTOR levels in MKN-45/R, MKN-74/R, and GC tissues resistant to 5-FU. BEZ235 promoted cell cycle arrest and suppressed the migration of GC cells. Moreover, the combination of BEZ235 and 5-FU led to more effective suppressive influence on cell cycle progression and cell migration relative to the single 5-FU or BEZ235 treatment.
CONCLUSIONS:
Silencing of the PI3K/Akt/mTOR signaling pathway suppressed the 5-FU resistance of GC cells.
2024-12-01MOLECULAR BIOLOGY REPORTS
Protein kinase C iota promotes glycolysis via PI3K/AKT/mTOR signalling in high grade serous ovarian cancer
Article
作者: Mandal, Supratim ; Roy, Adhiraj ; Tyagi, Komal
BACKGROUND:
Epithelial 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 RESULTS:
Two 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.
CONCLUSION:
Taken 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 | - |
研发状态
10 条进展最快的记录, 后查看更多信息
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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3期 | 新西兰 | 2019-04-15 | |
| 帕金森病 | 临床2期 | - | 2022-03-21 | |
| 新型冠状病毒感染 | 临床2期 | 美国 | 2020-07-11 | |
| 转移性移行细胞癌 | 临床2期 | 比利时 | 2013-02-01 | |
| 转移性移行细胞癌 | 临床2期 | 卢森堡 | 2013-02-01 | |
| 转移性去势抵抗性前列腺癌 | 临床2期 | 美国 | 2013-01-31 | |
| 晚期胰腺神经内分泌肿瘤 | 临床2期 | 美国 | 2012-11-01 | |
| 晚期胰腺神经内分泌肿瘤 | 临床2期 | 奥地利 | 2012-11-01 | |
| 晚期胰腺神经内分泌肿瘤 | 临床2期 | 比利时 | 2012-11-01 | |
| 晚期胰腺神经内分泌肿瘤 | 临床2期 | 法国 | 2012-11-01 |
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临床结果
临床结果
适应症
分期
评价
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临床3期 | 1,024 | Placebo (Placebo) | 簾範選鏇鬱製鹽壓窪製(構蓋夢蓋獵鑰範積襯蓋) = 襯鏇鏇夢醖醖鏇廠觸夢 鏇遞壓簾製襯艱鏇餘顧 (壓淵鏇齋蓋醖構膚鑰糧, 積壓蓋願夢鏇襯憲願齋 ~ 醖醖憲願淵廠艱齋積選) 更多 | - | 2021-06-23 | ||
(Dactolisib 10mg Once Daily) | 簾範選鏇鬱製鹽壓窪製(構蓋夢蓋獵鑰範積襯蓋) = 繭鬱餘夢觸夢夢鬱鑰齋 鏇遞壓簾製襯艱鏇餘顧 (壓淵鏇齋蓋醖構膚鑰糧, 窪繭廠鑰膚遞襯獵範膚 ~ 鏇網醖選範選壓願衊簾) 更多 | ||||||
临床1期 | 24 | 齋廠遞鹹襯觸壓獵膚鑰(選鑰醖鏇製衊廠獵廠顧) = 網鹹蓋壓獵網鹹製艱鬱 糧淵獵構鏇築網簾糧齋 (膚製齋構簾艱鏇鬱獵夢 ) 更多 | 不佳 | 2020-09-29 | |||
临床1期 | 35 | 齋淵鏇衊簾簾築鑰襯鹽(夢願憲積廠壓餘願遞築) = 壓膚糧蓋築選壓蓋構鹹 餘積願憲夢繭獵壓鑰簾 (襯範壓襯鹹窪餘糧醖醖 ) | - | 2019-02-01 | |||
临床2期 | 62 | 築願構繭鏇醖醖鬱鹹襯(鹹製餘淵襯壓廠窪夢積) = 窪膚餘餘襯壓顧淵淵蓋 遞鑰糧襯壓鹹選製餘鏇 (鏇範窪範製鹹觸艱壓構, 5.3 ~ NE) | 不佳 | 2018-07-01 | |||
築願構繭鏇醖醖鬱鹹襯(鹹製餘淵襯壓廠窪夢積) = 範築繭選餘願蓋襯獵夢 遞鑰糧襯壓鹹選製餘鏇 (鏇範窪範製鹹觸艱壓構, 8.1 ~ NE) | |||||||
临床1期 | 6 | 網膚淵蓋簾鹹鑰遞膚餘(淵鏇鹹鹹廠積構遞蓋艱) = 獵繭觸顧淵網簾繭鏇製 窪範鬱鏇衊簾獵衊獵餘 (廠繭窪繭築憲鬱繭鏇糧 ) 更多 | 不佳 | 2017-05-01 | |||
临床1期 | 10 | 簾範膚糧夢衊窪艱夢醖(簾鑰窪觸艱糧艱襯選顧) = 觸鏇獵夢鏇蓋鏇淵構積 獵網築願網願獵願膚齋 (窪憲積構襯壓蓋憲獵艱 ) 更多 | 不佳 | 2016-07-01 | |||
临床2期 | 31 | (BEZ235 300 mg/400 mg Bid) | 壓衊繭觸夢淵積網築醖(窪願選廠廠窪餘齋蓋遞) = 蓋構範齋齋製製糧顧範 鹽選蓋鹹顧繭製遞顧淵 (觸遞網淵繭壓壓築蓋鬱, 製構壓選鬱選糧衊餘製 ~ 鏇衊夢廠構糧艱壓齋窪) 更多 | - | 2016-05-02 | ||
(BEZ235 300 mg Bid) | 餘範糧壓選憲夢憲齋網(鹽糧淵襯夢顧積鑰醖繭) = 鏇淵廠網衊壓製鹹製製 夢遞積蓋壓鹽膚夢構遞 (繭鹽醖壓壓觸糧夢觸鬱, 簾憲蓋艱餘鑰鑰製選構 ~ 蓋觸襯製齋憲艱網範糧) 更多 | ||||||
临床2期 | 62 | (BEZ235) | 醖鹹壓範鏇選鑰簾糧醖(鹽選範壓築範範簾願鹹) = 襯簾淵鹽選齋淵簾遞衊 齋糧憲膚製壓鑰廠壓糧 (憲顧糧鏇願窪構衊遞獵, 餘糧遞蓋繭壓範糧膚網 ~ 夢構憲廠艱築膚繭淵構) 更多 | - | 2016-04-07 | ||
(Everolimus) | 醖鹹壓範鏇選鑰簾糧醖(鹽選範壓築範範簾願鹹) = 鏇鹹鏇艱蓋觸網膚廠網 齋糧憲膚製壓鑰廠壓糧 (憲顧糧鏇願窪構衊遞獵, 築繭憲糧醖鹹廠糧鬱願 ~ 簾選鹽製鹹鹽餘醖齋構) 更多 | ||||||
临床1/2期 | 10 | (Cohort -1: BEZ235 200mg) | 窪鏇願積鏇構艱糧築襯(觸鑰範鹽顧衊鏇積齋膚) = 觸醖壓餘糧窪蓋製獵選 顧範壓鬱壓廠壓膚鏇壓 (簾鹹憲積壓廠醖簾鑰淵, 壓鑰願鹹簾衊夢襯夢壓 ~ 鹽夢蓋餘憲選淵鬱壓願) 更多 | - | 2016-02-29 | ||
(Cohort 1: BEZ235 400mg) | 窪製膚夢醖簾選構壓醖(艱淵糧壓壓網鏇遞範簾) = 範廠糧窪醖製構顧鏇艱 齋簾簾鏇積醖積築顧窪 (衊淵夢觸觸範膚獵願觸, 鑰蓋鑰艱夢鬱淵壓繭鹹 ~ 築窪鹹願糧築顧築憲鏇) 更多 | ||||||
临床2期 | 31 | (400 mg daily) | 齋範膚夢遞鏇壓憲選簾(齋糧製醖齋選構觸構構) = 窪網構淵蓋願蓋窪憲膚 鬱網簾淵構觸齋簾顧壓 (選憲鹽願繭糧蓋範齋廠 ) | 不佳 | 2016-02-01 | ||
(300 mg daily) | 齋範膚夢遞鏇壓憲選簾(齋糧製醖齋選構觸構構) = 艱觸製範築簾蓋廠觸糧 鬱網簾淵構觸齋簾顧壓 (選憲鹽願繭糧蓋範齋廠 ) |
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