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Using lead-to-hit optimization, we identified a new Pannexin 1 inhibitor with superior specificity and potency compared with the commonly used inhibitors. We also described the structure-activity relationship of this new compound and revealed Trp74 residue of Pannexin 1 as the interacting site. Using a DSS-induced colitis mouse model, we further present this new Pannexin 1 inhibitor as a proof-of-principle strategy for treating colitis.
Advanced Science, 2024
We provide an updated review discussing Panx1's unique channel properties, diverse patho-physiological roles in nervous, immune, and cardiovascular systems, multiple context-specific activation mechanisms, and the biophysical implications from the recently revealed cyro-EM structures.
Biochemical Society Transactions, 2023
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我們發現Gq耦合蛋白受體可經由特殊細胞訊息傳遞路徑 Gq-Rho-mDia-HDAC6 而活化 Panx1 通道，同時去乙醯化可作為一種活化離子通道的新型分子機制。
Nature Communications, 2021
我們的研究指出常用的利尿劑/抗高血壓藥物 spironolactone 會抑制 Panx1 通道，進而在短期內拮抗交感神經活化導致的血壓上升。
Circulation Research, 2018
Cell Death & Disease, 2024
Journal of General Physiology, 2018
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