更新于：2024-05-01
caspase 3
半胱天冬酶-3
更新于：2024-05-01
基本信息
别名 半胱氨酸天冬氨酸蛋白酶3、Apopain、CASP-3 + [15] |
简介 Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:7596430, PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120). Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins (PubMed:7596430, PubMed:18723680, PubMed:20566630, PubMed:23650375). At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond (PubMed:7774019, PubMed:7596430, PubMed:10497198, PubMed:16374543). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9 (PubMed:7596430). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (PubMed:35446120, PubMed:35338844). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:33725486). |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
A Double-Blind, Placebo-Controlled, Parallel Design Phase 3 Study to Assess the Efficacy, Safety, Tolerability, and Pattern of Use of SM-1 in Adult Subjects With a History of Transient Insomnia
评价富马酸奥比特嗪肠溶微丸胶囊（SM-1）治疗晚期小肠腺癌（SBA）的有效性、安全性及药效动力学特征的开放性、单臂、多中心、Ⅱ期临床试验
富马酸奥比特嗪肠溶微丸胶囊（SM-1）联合替莫唑胺在难治或复发胶质母细胞瘤受试者中的安全性、药代动力学 I 期临床研究
100 项与 caspase 3 相关的临床结果
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100 项与 caspase 3 相关的转化医学
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2024-12-01Journal of enzyme inhibition and medicinal chemistry
Design, synthesis, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers.
Article
作者: Naglaa M Ahmed ; Mosaad S Mohamed ; Samir M Awad ; Rania H Abd El-Hameed ; Neama A Abd El-Tawab ; Mohamed S Gaballah ; Ahmed M Said
Herein, a novel series of 6-amino-5-cyano-2-thiopyrimidines and condensed pyrimidines analogues were prepared. All the synthesized compounds (1a-c, 2a-c, 3a-c, 4a-r and 5a-c) were evaluated for in vitro anticancer activity by the National Cancer Institute (NCI; MD, USA) against 60 cell lines. Compound 1c showed promising anticancer activity and was selected for the five-dose testing. Results demonstrated that compound 1c possessed broad spectrum anti-cancer activity against the nine cancerous subpanels tested with selectivity ratio ranging from 0.7 to 39 at the GI50 level with high selectivity towards leukaemia. Mechanistic studies showed that Compound 1c showed comparable activity to Duvelisib against PI3Kδ (IC50 = 0.0034 and 0.0025 μM, respectively) and arrested cell cycle at the S phase and displayed significant increase in the early and late apoptosis in HL60 and leukaemia SR cells. The necrosis percentage showed a significant increase from 1.13% to 3.41% in compound 1c treated HL60 cells as well as from 1.51% to 4.72% in compound 1c treated leukaemia SR cells. Also, compound 1c triggered apoptosis by activating caspase 3, Bax, P53 and suppressing Bcl2. Moreover, 1c revealed a good safety profile against human normal lung fibroblast cell line (WI-38 cells). Molecular analysis of Duvelisib and compound 1c in PI3K was performed. Finally, these results suggest that 2-thiopyrimidine derivative 1c might serve as a model for designing novel anticancer drugs in the future.
2024-12-01Journal of enzyme inhibition and medicinal chemistry
A multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations.
Article
作者: Fatma A Elshibani ; Abdullah D Alamami ; Hamdoon A Mohammed ; Rabab Ahmed Rasheed ; Radwa M El Sabban ; Mohamed A Yehia ; Sherif S Abdel Mageed ; Taghreed A Majrashi ; Eslam B Elkaeed ; Mahmoud A El Hassab ; Wagdy M Eldehna ; Mohamed K El-Ashrey
The Libyan Strawberry, Arbutus pavarii Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.54 GAE and 36.2 RE of the phenolics and flavonoids. LC-MS analysis identified 35 compounds belonging to phenolic acids, procyanidins, and flavonoid glycosides. Gallic acid, procyanidin dimer B3, β-type procyanidin trimer C, and quercetin-3-O-glucoside were the major constituents of the plant extract. ARB administration to paracetamol (PAR)-intoxicated rats reduced serum ALT, AST, bilirubin, hepatic tissue MDA and proinflammatory markers; TNF-α and IL-6 with an increase in tissue GSH level and SOD activity. Histological and immunohistochemical studies revealed that ARB restored the liver histology and significantly reduced the tissue expression of caspase 3, IL-1B, and NF-KB in PAR-induced liver damage. Docking analysis disclosed good binding affinities of some compounds with XO, COX-1, 5-LOX, and PI3K.
2024-12-01Journal of enzyme inhibition and medicinal chemistry
Design, synthesis, and apoptotic antiproliferative action of new 1,2,3-triazole/1,2,4-oxadiazole hybrids as dual EGFR/VEGFR-2 inhibitors.
Article
作者: Mohamed A Mahmoud ; Anber F Mohammed ; Ola I A Salem ; Tahani Mazyad Almutairi ; Stefan Bräse ; Bahaa G M Youssif
A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids (7a-o) was developed as dual inhibitors of EGFR/VEGFR-2. Compounds 7a-o were evaluated as antiproliferative agents with Erlotinib as the reference drug. Results demonstrated that most of the tested compounds showed significant antiproliferative action with GI50 values ranging from 28 to 104 nM, compared to Erlotinib (GI50 = 33 nM), and compounds 7i-m were the most potent. Compounds 7h, 7i, 7j, 7k, and 7l were evaluated as dual EGFR/VEGFR-2 inhibitors. These in vitro experiments demonstrated that compounds 7j, 7k, and 7l are potent antiproliferative agents that may operate as dual EGFR/VEGFR-2 inhibitors. Compounds 7j, 7k, and 7l were evaluated for their apoptotic potential activity, where findings indicated that compounds 7j, 7k, and 7l promote apoptosis by activating caspase-3, 8, and Bax and down-regulating the anti-apoptotic Bcl-2. Molecular docking simulations show the binding mode of the most active antiproliferative compounds within EGFR and VEGFR-2 active sites.
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