MCE 产品发表的高分文章锦集 | MedChemExpress
Combination of ERK and autophagyinhibition as a treatment approach for pancreatic cancer.
ARS-1620 purchased from MCE.
胰腺导管腺癌(PDAC)的特征是 KRAS 和自噬依赖的致瘤生长，但 KRAS 在自噬中的作用尚未确定。令人惊讶的是，研究人员发现 KRAS 的抑制增加了自噬通量，其效应物 ERK MAPK 的药理抑制也增加了自噬通量。此外，研究人员还证明 KRAS 抑制或 ERK 抑制都会降低糖酵解和线粒体功能。因此推测， ERK 抑制可能因此增强PDAC 对自噬的依赖，部分破坏其他 KRAS 或 ERK 驱动的代谢过程。研究人员发现自噬抑制剂氯喹与特异性自噬调节因子的遗传或药理抑制协同增强了 ERK 抑制剂介导 kras 驱动的 PDAC 抗肿瘤活性的能力。进而得出结论，同时阻断 ERK MAPK 和自噬过程的药物抑制剂组合可能是治疗 PDAC 的有效方法。
Researchers show that either KRAS suppression or ERK inhibition decreased both glycolytic and mitochondrial functions. Therefore,researchers speculated that ERK inhibition might enhance PDAC dependence onautophagy, in part by impairing other KRAS- or ERK-driven metabolic processes. Autophagy inhibitor chloroquine and genetic or pharmacologic inhibition of specificautophagy regulators synergistically enhanced the ability of ERK inhibitors tomediate antitumor activity in KRAS-driven PDAC. Accordingly, combinations of pharmacologic inhibitors that concurrently block both ERK MAPK and autophagic processes that are upregulated in response to ERK inhibition maybe effective treatments for PDAC.
Cryo-EM Structure and Assembly of anExtracellular Contractile Injection System.
Protease Inhibitor Cocktail purchased from MCE.
收缩注射系统(CISs)是一种细胞穿刺纳米器件，它与收缩尾噬菌体具有同源性。发光毒力盒(PVC)是细菌和古生菌中都存在的一组细胞外 CISs。研究人员报告了来自P. asymbiotica 的完整 PVC 的低温电子显微镜结构。这个超过 10-MDa 的装置类似于一个简化的 T4 噬菌体尾，包含一个六角形的基板复合体，其中有 6 根纤维和一个 117 纳米管的覆盖体。PVC 的一个显著特征是管状蛋白和鞘状蛋白都存在三种变异，这表明它们在进化过程中具有功能专门化。末端的六美冠与内管状物的最上层对接，用六个伸缩臂将外鞘锁在预收缩状态。研究人员在 PVC 上的研究结果为广泛理解 CISs 一般机制使用，提供了一个框架，并为将它们用作生物或治疗应用中的传递工具铺平了道路。
Researchers report the cryo-EM structure of an intact PVC from P. asymbiotica. This over10-MDa device resembles a simplified T4 phage tail, containing a hexagonalbaseplate complex with six fibers and a capped 117-nanometer sheath-tube trunk.The terminal hexameric cap docks onto the topmost layer of the inner tube andlocks the outer sheath in pre-contraction state with six stretching arms. Researchers result on the PVC provide a framework for understanding the general mechanism of widespread CISs and pave the way for using them as delivery tools inbiological or therapeutic applications.
Entinostat purchased from MCE.
细胞质中出现 DNA，通常是微生物感染的一种迹象，可通过循环 GMP-AMP 合成酶(cGAS)快速检测到，从而引发抗感染免疫反应。然而，自我 DNA 对 cGAS 的慢性激活会导致严重的自身免疫性疾病，目前尚无有效的治疗方法。重要的是，证明阿司匹林可以直接乙酰化 cGAS，并有效抑制 cGAS 介导的免疫反应。最后，研究人员证明阿司匹林可以有效抑制 aicardii - goutieres 综合征(AGS)患者细胞和 AGS 小鼠模型中自我 DNA 诱导的自身免疫。因此，研究表明乙酰化有助于 cGAS 的活性调节，并为治疗 DNA 介导的自身免疫性疾病提供了一种潜在的治疗方法。
Researchers report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. cGAS isdeacetylated in response to DNA challenges. Importantly, we show that aspirincan directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, researchers demonstrate that aspirin can effectivelysuppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Consequently, the study reveals that acetylation contributes to cGAS activity regulation and provides a potentialtherapy for treating DNA-mediated autoimmune diseases.
