Key result
Compound 80, a highly potent and selective Kv2.1 inhibitor (IC50 = 0.07 μM), decreased apoptosis in HEK293 cells and markedly reduced infarct volume in an MCAO rat model of ischemic stroke.
Why the study?
Inhibiting Kv2.1 is a potential strategy to prevent cell death and achieve neuroprotection in ischemic stroke.
Answers are grounded in this paper and cite their sources.
Compound 80 is a highly potent and selective Kv2.1 inhibitor that demonstrates neuroprotective effects and reduces infarct volume in a rat model of ischemic stroke.
Kv2.1 is involved in regulating neuronal excitability and neuronal cell apoptosis, and inhibiting Kv2.1 is a potential strategy to prevent cell death and achieve neuroprotection in ischemic stroke. In this work, a series of novel benzamide derivatives were designed and synthesized as Kv2.1 inhibitors, and extensive structure–activity relationships led to highly potent and selective Kv2.1 inhibitors having IC 50 values of 10 –8 M. Among them, compound 80 (IC 50 = 0.07 μM, selectivity >130 fold over other K +, Na +, and Ca 2+ ion channels) was able to decrease the apoptosis of HEK293/Kv2.1 cells induced by H 2 O 2 . Furthermore, its anti-ischemic efficacy was demonstrated as it markedly reduced the infarct volume in MCAO rat model. Additionally, compound 80 possessed appropriate plasma PK parameters. It could serve as a probe to investigate Kv2.1 pathological functions and deserved to be further explored.
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Zhou et al. (2023) studied Ischemic stroke. Compound 80 (benzamide derivative) was evaluated on Kv2.1 inhibition, cell apoptosis, and infarct volume. Compound 80, a highly potent and selective Kv2.1 inhibitor (IC50 = 0.07 μM), decreased apoptosis in HEK293 cells and markedly reduced infarct volume in an MCAO rat model of ischemic stroke.
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