WEHI-9625 是一种首创的，三环砜小分子凋亡抑制剂，EC50 值为 69 nM。WEHI-9625 与 VDAC2 结合可促进其抑制小鼠 BAK 诱导的细胞凋亡的能力，但对人 BAK 和与凋亡效应密切相关的 BAX 因子均完全无效。
WEHI-9625 is a tricyclic sulfone, first-in-class inhibitor of apoptosis with an EC50 of 69 nM. WEHI-9625 binds to VDAC2 and promotes its ability to inhibit apoptosis driven by mouse BAK. WEHI-9625 is completely inactive against both human BAK and the closely related apoptosis effector BAX[1].
WEHI-9625 (0-10 µM; Mcl1-/-Bax-/- MEFs cells) treatment could prevent cell death mediated by BAK and potently inhibits BIM BH3-induced loss of mitochondrial membrane potential in Bax-/-, but not Bak-/-, cells[1].
WEHI-9625 demonstrates that blocking apoptosis at an early stage was both advantageous and pharmacologically tractable[1].
[1]. van Delft MF, et al. A small molecule interacts with VDAC2 to block mouse BAK-driven apoptosis. Nat Chem Biol. 2019 Oct 7.
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