Duan, Ying-Chao; Jin, Lin-Feng; Ren, Hong-Mei; Zhang, Shao-Jie; Liu, Yue-Jiao; Xu, Yong-Tao; He, Zi-Hao; Song, Yu; Yuan, Hang; Chen, Shu-Hui; Guan, Yuan-Yuan published an article in 2021. The article was titled 《Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer》, and you may find the article in European Journal of Medicinal Chemistry.Safety of Pyridin-3-ylboronic acid The information in the text is summarized as follows:
A series of novel LSD1/HDAC bifunctional inhibitors with a styrylpyridine skeleton I [meta-, para-substituted; X = CH, N; R = H, 3-thienyl, 2-hydroxy-5-fluorophenyl, etc; R1 = H, F], II and III [R2 = H, F; R3 = H, Me, F3C; R4 = H, F, HO, MeO] were designed and synthesized based on our previously reported LSD1 inhibitors. The representative compounds I [para-substituted; X = N; R = 2-hydroxyphenyl, 2-fluoro-4-methylphenyl; R1 = H] showed potent activity against LSD1 and HDAC at both mol. and cellular level and displayed high selectivity against MAO-A/B. Compounds I [para-substituted; X = N; R = 2-hydroxyphenyl, 2-fluoro-4-methylphenyl; R1 = H] demonstrated potent antiproliferative activities against MGC-803 and HCT-116 cancer cell lines. Compound I [para-substituted, X = N, R = 2-fluoro-4-methylphenyl, R1 = H] showed superior in-vitro anticancer potency against a panel of gastric cancer cell lines than ORY-1001 and SP-2509 with IC50 values ranging from 0.23 to 1.56μM. Compounds I [para-substituted; X = N; R = 2-hydroxyphenyl, 2-fluoro-4-methylphenyl; R1 = H] significantly modulated the expression of Bcl-2, Bax, Vimentin, ZO-1 and E-cadherin, induced apoptosis, reduced colony formation and suppressed migration in MGC-803 cancer cells. In addition, preliminary absorption, distribution, metabolism, excretion (ADME) studies revealed that compounds I [para-substituted; X = N; R = 2-hydroxyphenyl, 2-fluoro-4-methylphenyl; R1 = H] showed acceptable metabolic stability in human liver microsomes with minimal inhibition of cytochrome P450s (CYPs). Those results indicated that compound I [para-substituted, X = N, R = 2-fluoro-4-methylphenyl, R1 = H] could be a promising lead compound for further development as a therapeutic agent in gastric cancers via LSD1 and HDAC dual inhibition. In the part of experimental materials, we found many familiar compounds, such as Pyridin-3-ylboronic acid(cas: 1692-25-7Safety of Pyridin-3-ylboronic acid)
Pyridin-3-ylboronic acid(cas: 1692-25-7) belongs to pyridine. Pyridines form stable salts with strong acids. Pyridine itself is often used to neutralize acid formed in a reaction and as a basic solvent. Safety of Pyridin-3-ylboronic acid