已经提出MCC950作为特异性小分子抑制剂,其可以选择性地阻断NLRP3炎性体活化。然而,其作用的确切机制仍然模棱两可。积累的研究表明,氯化物外排依赖性ASC斑点寡聚化和钾外排依赖性caspase-1的活化是两个相对独立的,但NLRP3炎性体激活必不可少的事件。先前的研究表明,MCC950对钾流出及其随之而来的事件如NEK7和NLRP3之间的相互作用的影响是有限的。然而,抑制氯离子细胞内通道依赖性氯离子流出导致炎症反应的改变,其功能类似于MCC950。基于这些发现,我们对MCC950的功能可能与氯化物流出相关的理解有了新的见解,氯化物细胞内通道,或其他作用于氯化物流出上游的目标。
MCC950 has been proposed as a specific small molecule inhibitor that can selectively block NLRP3 inflammasome activation. However, the exact mechanism of its action is still ambiguous. Accumulating investigations imply that chloride efflux-dependent ASC speck oligomerization and potassium efflux-dependent activation of caspase-1 are the two relatively independent, but indispensable events for NLRP3 inflammasome activation. Previous studies suggested that influence of MCC950 on potassium efflux and its consequent events such as interaction between
NEK7 and NLRP3 are limited. However, inhibiting chloride intracellular channel-dependent chloride efflux leads to a modification of inflammatory response, which is similar to the function of MCC950. Based on these findings, we shed new insights on the understanding of MCC950 that its function might correlate with chloride efflux, chloride intracellular channels, or other targets that act upstream of chloride efflux.