A computational perspective for tailor-made selective Mcl-1 and Bcl …
2022年4月5日 · In view of the crucial role of Mcl-1 in tumor survival and resistance as well as the importance of Bcl-XL in platelets homeostasis, an appropriate tuning of binding selectivity between Mcl-1 and Bcl-XL is crucial to discover safer anticancer candidates.
Co-targeting BCL-XL and MCL-1 with DT2216 and AZD8055
2023年1月2日 · We, therefore, aimed to develop an effective and safe strategy targeting these anti-apoptotic proteins with DT2216 (our platelet-sparing BCL-X L degrader) and AZD8055 (an mTOR inhibitor) to avoid...
MCL-1 抑制剂与 BCL-2/BCL-XL 或 MAPK 通路抑制剂的协同作用增 …
急性髓系白血病 (aml) 是一种血液系统恶性肿瘤，其特征是异常髓系前体细胞过度增殖，并伴有分化阻滞和细胞凋亡抑制。抗凋亡 mcl-1 蛋白的表达增加被证明对 aml 细胞的持续存活和扩增至关重要。因此，在本文中，我们检测了 mcl-1 特异性抑制剂 s63845 在单药治疗中以及与 bcl-2/bcl-xl 抑制剂 abt-737 联合 ...
The identification of BCL-XL and MCL-1 as key anti-apoptotic
2023年10月28日 · Collectively, our study identifies that BCL-XL and MCL-1 are the key anti-apoptotic proteins in medulloblastoma, which mediate distinct protective roles. While BCL-XL has a first-line role in...
Mcl-1 and Bcl-xL are essential for survival of the developing
2018年10月25日 · We used Nestin-mediated, nervous system-specific conditional deletion of mcl-1, bcl-x or both to identify their distinct and overlapping roles. Individual conditional deletion of mcl-1 (MKO) and...
Mcl-1 和 Bcl-xL 在多阶段调节巨核细胞谱系的 Bak/Bax 依赖性细胞 …
ABT-737 是一种 Bcl-xL/Bcl-2/Bcl-w 抑制剂，仅在成年野生型小鼠中引起血小板减少症，但在 Mcl-1 敲除小鼠中进一步诱导大量成熟巨核细胞凋亡，导致严重的出血性贫血。 如果下游细胞凋亡刽子手 Bak 和 Bax 也有缺陷，所有这些表型都会完全恢复。 体外研究表明，Jak 通路维持 Mcl-1 和 Bcl-xL 的表达水平，防止巨核细胞凋亡。 同样，两者都参与网状血小板存活，而由于 Mcl-1 的快速蛋白酶体降解，血小板存活依赖于 Bcl-xL。 总之，Mcl-1 和 Bcl-xL 调节巨核细胞谱系的存 …
Mcl-1 and Bcl-xL cooperatively maintain integrity of ... - PubMed
Mcl-1 and Bcl-xL are two major anti-apoptotic Bcl-2 family proteins expressed in the liver and cooperatively control hepatic integrity during liver development and in adult liver homeostasis in a gene dose-dependent manner.
The identification of BCL-XL and MCL-1 as key anti-apoptotic
2023年10月28日 · Collectively, our study identifies that BCL-XL and MCL-1 are the key anti-apoptotic proteins in medulloblastoma, which mediate distinct protective roles. While BCL-XL has a first-line role in protecting cells from apoptosis basally, MCL-1 represents a second line of defence that compensates for BCL-XL upon its inhibition.
Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts ... - PubMed
In multiple myeloma cell lines (n = 21), BCL-2 is expressed but sensitivity to venetoclax correlated with high BCL-2 and low BCL-XL or MCL-1 expression. Multiple myeloma cells that coexpress BCL-2 and BCL-XL were resistant to venetoclax but sensitive to a …
Targeting MCL-1 in cancer: current status and perspectives
Myeloid leukemia 1 (MCL-1) is an antiapoptotic protein of the BCL-2 family that prevents apoptosis by binding to the pro-apoptotic BCL-2 proteins. Overexpression of MCL-1 is frequently observed in many tumor types and is closely associated with tumorigenesis, poor prognosis and drug resistance.