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Target of MCC950 in Inhibition of NLRP3 Inflammasome Activation: a Literature Review

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Abstract

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.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81873130, No. 81573733, No. 81804025), Tianjin Municipal Natural Science Foundation (No. 18JCYBJC94500), Scientific and Technological Research Program of Tianjin Municipal Education Commission (No. 2017KJ164), and 2017 Annual Graduate Students Innovation Fund (School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; No. CXJJLX201701).

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  1. Danbin Wu and Yefei Chen contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China

    Danbin Wu, Yefei Chen, Yingxin Sun, Qing Gao, Huhu Li, Zhengfei Yang, Yangxue Wang & Xijuan Jiang

  2. International Exchanges Department & International Education College, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China

    Bin Yu

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  1. Danbin Wu
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Wu, D., Chen, Y., Sun, Y. et al. Target of MCC950 in Inhibition of NLRP3 Inflammasome Activation: a Literature Review. Inflammation 43, 17–23 (2020). https://doi.org/10.1007/s10753-019-01098-8

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