预约演示
更新于：2025-05-16
Gemcitabine elaidate
吉西他滨反油酸酯
更新于：2025-05-16
概要
基本信息
原研机构 |
在研机构- |
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C27H43F2N3O5 |
InChIKeyHESSNRGIEVBPRB-QDDPNBLJSA-N |
CAS号210829-30-4 |
关联
8
项与 吉西他滨反油酸酯 相关的临床试验NCT01641575
A Phase I Open-Label, Ascending Dose Cohort Study of Gemcitabine Elaidate and Cisplatin in Patients With Advanced Solid Tumors Followed by an Expanded Cohort of Patients With Stage IIIb/IV NSCLC.
NL-OMON34352
A phase I, open-label, two-stage, randomized, crossover, comparative pharmacokinetic and safety study of two formulations of CO-1.01 for injection in patients with advanced solid tumors. - Phase I PK study of CO-1.01 in patients with advanced solid tumors.
NCT01392976
A Phase I, Open-Label, Two-stage, Randomized, Crossover, Comparative Pharmacokinetic and Safety Study of Two Formulations of CO-1.01 for Injection in Patients With Advanced Solid Tumors
100 项与 吉西他滨反油酸酯 相关的临床结果
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100 项与 吉西他滨反油酸酯 相关的转化医学
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100 项与 吉西他滨反油酸酯 相关的专利（医药）
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27
项与 吉西他滨反油酸酯 相关的文献（医药）2024-08-02Nucleosides, nucleotides & nucleic acids
Effects of nucleoside analogues, lipophilic prodrugs and elaidic acids on core signaling pathways in cancer cells
Article
作者: Giovannetti, Elisa ; Peters, Godefridus J. ; van der Sande, Claudine ; Frańczak, Marika A.
OBJECTIVES:
Nucleoside analogs such as gemcitabine (GEM; dFdC) and cytarabine (Ara-C) require nucleoside transporters to enter cells, and deficiency in equilibrative nucleoside transporter 1 (ENT1) can lead to resistance to these drugs. To facilitate transport-independent uptake, prodrugs with a fatty acid chain attached to the 5'-position of the ribose group of gemcitabine or cytarabine were developed (CP-4126 and CP-4055, respectively). As antimetabolites can activate cellular survival pathways, we investigated whether the prodrugs or their side-chains had similar or decreased effects.
METHODS:
Two cell lines A549 (non-small cell lung cancer) and WiDr (colon cancer cells) were exposed for 2-24hr to IC50 concentrations of GEM, Ara-C, CP-4126, CP4055 and elaidic acid (EA) concentrations corresponding to the CP-4126 and CP-4055 IC50. Cells were harvested and analyzed for proteins in cell survival pathways (p-AKT/AKT, p-ERK/ERK, p-P38/P38, GSK-3β/pGSK-3β) by using Western Blotting.
RESULTS:
All drugs and their derivatives showed time- and cell-line-dependent effects. In A549 cells, GEM, CP-4126 and EA-4126 decreased the p-AKT/AKT ratio at 2 and 24 hr. For the p-ERK/ERK ratio, GEM, EA-4126, Ara-C, CP-4045 and EA-4055 exposure led to an increase after 6 hr in A549 cells. Interestingly, Ara-C, CP-4055 and EA-4055 decreased p-ERK/ERK ratio in WiDr cells after 4 hr. In A549 cells, the p-GSK-3β/GSK-3β ratio decreased after exposure to Ara-C and CP-4055 but in WiDr cells increased after 24 hr. In A549 cells treatment with Ara-C, CP-4055 and EA-4126 decreased the p-P38/P38 after 6 hr.
CONCLUSIONS:
The findings suggest that both parent drugs, prodrugs, and the EA chain influence cell survival and signaling pathways.
2024-03-29Cell Death Discovery
Gemcitabine elaidate and ONC201 combination therapy for inhibiting pancreatic cancer in a KRAS mutated syngeneic mouse model.
Article
作者: Staller, Dalton W ; Shrestha, Prakash ; Kumar, Virender ; Sethi, Bharti ; Mahato, Ram I
Approximately 90% of pancreatic cancer (PC) contain KRAS mutations. Mutated KRAS activates the downstream oncogenic PI3K/AKT and MEK signaling pathways and induces drug resistance. However, targeting both pathways with different drugs can also lead to excessive toxicity. ONC201 is a dual PI3K/AKT and MEK pathway inhibitor with an excellent safety profile that targets death receptor 5 (DR5) to induce apoptosis. Gemcitabine (GEM) is a first-line chemotherapy in PC, but it is metabolically unstable and can be stabilized by a prodrug approach. In this study, phospho-Akt, phospho-mTOR, and phospho-ERK protein expressions were evaluated in patient PDAC-tissues (n = 10). We used lipid-gemcitabine (L_GEM) conjugate, which is more stable and enters the cells by passive diffusion. Further, we evaluated the efficacy of L_GEM and ONC201 in PC cells and "KrasLSL-G12D; p53LoxP; Pdx1-CreER (KPC) triple mutant xenograft tumor-bearing mice. PDAC patient tissues showed significantly higher levels of p-AKT (Ser473), p-ERK (T202/T204), and p-mTOR compared to surrounding non-cancerous tissues. ONC201 in combination with L_GEM, showed a superior inhibitory effect on the growth of MIA PaCa-2 cells. In our in-vivo study, we found that ONC201 and L_GEM combination prevented neoplastic proliferation via AKT/ERK blockade to overcome chemoresistance and increased T-cell tumor surveillance. Simultaneous inhibition of the PI3K/AKT and MEK pathways with ONC201 is an attractive approach to potentiate the effect of GEM. Our findings provide insight into rational-directed precision chemo and immunotherapy therapy in PDAC.
2023-07-25ACS nano
Transforming Cancer-Associated Fibroblast Barrier into Drug Depots to Boost Chemo-Immunotherapy in "Shooting Fish in a Barrel" Pattern.
Article
作者: Liu, Jinhu ; Liang, Shuang ; Liu, Yongjun ; Gao, Tong ; Yuan, Shijun ; Xia, Zhenxing ; Liu, Shujun ; Liu, Meichen ; Fu, Shunli ; Huang, Xinyan ; Mu, Weiwei ; Zhang, Na
The cancer-associated fibroblast (CAF) barrier in pancreatic ductal adenocarcinoma (PDAC) greatly restricts clinical outcomes. Major obstacles to PDAC treatment include restricted immune cell infiltration and drug penetration and the immunosuppressive microenvironment. Here, we reported a "shooting fish in a barrel" strategy by preparing a lipid-polymer hybrid drug delivery system (PI/JGC/L-A) that could overcome the CAF barrier by turning it into a "barrel" with antitumor drug depot properties to alleviate the immunosuppressive microenvironment and increase immune cell infiltration. PI/JGC/L-A is composed of a pIL-12-loaded polymeric core (PI) and a JQ1 and gemcitabine elaidate coloaded liposomal shell (JGC/L-A) that has the ability to stimulate exosome secretion. By normalizing the CAF barrier to create a CAF "barrel" with JQ1, stimulating the secretion of gemcitabine-loaded exosomes from the CAF "barrel" to the deep tumor site, and leveraging the CAF "barrel" to secrete IL-12, PI/JGC/L-A realized effective drug delivery to the deep tumor site, activated antitumor immunity at the tumor site, and produced significant antitumor effects. In summary, our strategy of transforming the CAF barrier into antitumor drug depots represents a promising strategy against PDAC and might benefit the treatment of any tumors facing a drug delivery barrier.
1
项与 吉西他滨反油酸酯 相关的新闻（医药）2022-11-12
并购财报基因疗法申请上市医药出海
100 项与 吉西他滨反油酸酯 相关的药物交易
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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 |
|---|---|---|---|---|
| 转移性胰腺腺癌 | 临床2期 | 美国 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 阿根廷 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 澳大利亚 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 比利时 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 巴西 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 加拿大 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 法国 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 德国 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 意大利 | 2010-05-01 | |
| 转移性胰腺腺癌 | 临床2期 | 荷兰 | 2010-05-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 367 | (CO-1.01) | 壓顧顧廠齋製繭顧選鑰(窪淵範積艱製鑰衊淵膚) = 膚廠壓繭觸鹽膚餘網壓 觸遞鹽廠鏇繭簾積願觸 (廠鏇艱鬱膚範積築構遞, 鏇鏇獵範夢鬱醖製積鹽 ~ 網憲糧夢製憲顧衊糧壓) 更多 | - | 2014-04-17 | ||
(Gemcitabine) | 壓顧顧廠齋製繭顧選鑰(窪淵範積艱製鑰衊淵膚) = 範顧選構鏇網製鑰構簾 觸遞鹽廠鏇繭簾積願觸 (廠鏇艱鬱膚範積築構遞, 膚簾構壓簾網餘鏇顧築 ~ 觸鹽憲積糧觸夢鏇獵選) 更多 | ||||||
临床2期 | 367 | 簾製廠壓願鏇鏇齋膚艱(願鹹築蓋繭淵願憲構夢): HR = 0.994 (95% CI, 0.746 ~ 1.326) | 不佳 | 2013-05-20 | |||
Gemcitabine | |||||||
临床2期 | - | 範鬱憲膚鹽製範膚醖窪(鹽齋鏇鏇築構選鬱鬱範) = 製選衊蓋齋選糧範遞膚 顧願簾觸願鏇構構鏇製 (築膚範壓壓齋襯積蓋夢 ) | - | 2010-05-20 | |||
範鬱憲膚鹽製範膚醖窪(鹽齋鏇鏇築構選鬱鬱範) = 壓鏇鏇網構醖艱襯選憲 顧願簾觸願鏇構構鏇製 (築膚範壓壓齋襯積蓋夢 ) |
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