87375-91-5Relevant articles and documents
Permeant fluorescent probes visualize the activation of sarm1 and uncover an antineurodegenerative drug candidate
Cai, Yang,Cao, Sheng,Du, Yang,Hou, Yun Nan,Huang, Ke,Lee, Chi-Sing,Lee, Hon Cheung,Li, Wan Hua,Wang, Qian Wen,Wang, Sujing,Xie, Xu Jie,Zhang, Hongmin,Zhao, Yong Juan,Zhao, Zhi Ying,Zhu, Wen Jie
, (2021/06/30)
SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed and synthesized fluorescent conjugates of styryl derivative with pyridine to serve as substrates of SARM1, which exhibited large red shifts after conversion. With the conjugates, SARM1 activation was visualized in live cells following elevation of endogenous NMN or treatment with a cell-permeant NMN-analog. In neurons, imaging documented mouse SARM1 activation preceded vincristine-induced axonal degeneration by hours. Library screening identified a derivative of nisoldipine (NSDP) as a covalent inhibitor of SARM1 that reacted with the cysteines, especially Cys311 in its ARM domain and blocked its NMN-activation, protecting axons from degeneration. The Cryo-EM structure showed that SARM1 was locked into an inactive conformation by the inhibitor, uncovering a potential neuroprotective mechanism of dihydropyridines.
UV derivative spectrophotometric study of the photochemical degradation of nisoldipine
Marinkovic, Valentina,Agbaba, Danica,Karljikovic-Rajic, Katarina,Comor, Jozef,Zivanov-Stakic, Dobrila
, p. 128 - 133 (2007/10/03)
The photodecomposition of nisoldipine ((±)3-isobutyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-pyridine-3,5-dicarboxylate), whereby its 4-(2-nitrosophenyl) pyridine analogue is obtained as the photolytic product, was investigated under daylight exposure by means of UV derivative spectrophotometry. The optimal instrumental parameters (120 nm/min scan speed; 2 nm slit width; Δλ=10 nm and 5 s response time) for analogue derivative spectra were established for amplitudes 1D285 and 2D291 (measured to the baseline) of the nitroso analogue assay, as well as for 1D386 of the parent compound-nisoldipine assay. Using the first-order derivative spectrum, the minimum detectable amount of nitroso analogue in the presence of nisoldipine was equivalent to an impurity level of 5% and by the second-order derivative spectrum, the determination limit was equivalent to an impurity level of 2%. The degradation of nisoldipine followed within 30 days and the calculated maximal degradation rate was 1.6% per day for nisoldipine raw material, but significantly lower values of 0.19 and 0.15% per day were obtained for Nisoldin tablets (10 and 5 mg, respectively). Copyright (C) 2000 Elsevier Science S.A.
