Dehydronitrosonisoldipine is a derivative of nisoldipine, which retains calcium channel antagonist activity while also possessing the ability to inhibit sterile alpha and TIR motif-containing protein 1 (SARM1), thus making it a dual-bioactive compound[1]. Dehydronitrosonisoldipine irreversibly inhibits SARM1 activation by covalently modifying cysteine 311 of the SARM1 protein, thereby blocking downstream axonal degeneration (AxD) signaling pathways[2]. Dehydronitrosonisoldipine can be used to study the mechanisms of axonal degeneration associated with neurodegenerative diseases, such as exploring its role in chemotherapy-induced neuropathy (e.g., vincristine-induced neuropathy)[2].
References:
[1] Li W H, Huang K, Cai Y, et al. Permeant fluorescent probes visualize the activation of SARM1 and uncover an anti-neurodegenerative drug candidate[J]. Elife, 2021, 10: e67381.
[2] Feldman H C, Merlini E, Guijas C, et al. Selective inhibitors of SARM1 targeting an allosteric cysteine in the autoregulatory ARM domain[J]. Proceedings of the National Academy of Sciences, 2022, 119(35): e2208457119.
Dehydronitrosonisoldipine是尼索地平（Nisoldipine）的衍生物，在保留钙离子通道拮抗活性的同时，还具备抑制无菌α和TIR基序蛋白1（SARM1）的功能，因而成为一种双重生物活性化合物[1]。Dehydronitrosonisoldipine通过共价修饰SARM1蛋白半胱氨酸311位点，不可逆地抑制SARM1的激活，从而阻止下游轴突退化（AxD）信号通路[2]。Dehydronitrosonisoldipine能够用于研究神经退行性疾病相关的轴突退化机制，例如探索其在化疗药物（如长春新碱）诱导的神经病变中的作用[2]。