An article Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors WOS:000482845600016 published article about CARFILZOMIB; DESIGN in [Lei, Meng; Miao, Hang; Feng, Huayun] Nanjing Forestry Univ, Coll Sci, 159 Longpan Rd, Nanjing 210037, Jiangsu, Peoples R China; [Zhang, Haoyang; Du, Xiao; Zhou, Hui; Wang, Xueyuan; Zhu, Yongqiang] Nanjing Normal Univ, Coll Life Sci, 1 Wenyuan Rd, Nanjing 210046, Jiangsu, Peoples R China; [Wang, Jia; Shi, Jingmiao; Liu, Zhaogang; Zhu, Yongqiang] Jiangsu Chia Tai Fenghai Pharmaceut Co Ltd, 9 Weidi Rd, Nanjing 210046, Jiangsu, Peoples R China; [Shen, Jian] Nanjing Normal Univ, Coll Chem & Mat Sci, 1 Wenyuan Rd, Nanjing 210046, Jiangsu, Peoples R China in 2019, Cited 21. The Name is Pyrazine-2-carboxylic acid. Through research, I have a further understanding and discovery of 98-97-5. Name: Pyrazine-2-carboxylic acid
A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R-1, R-2, R-3, R-4 and R-5 positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC50, of 92.1 mu M.
About Pyrazine-2-carboxylic acid, If you have any questions, you can contact Lei, M; Zhang, HY; Miao, H; Du, X; Zhou, H; Wang, J; Wang, XY; Feng, HY; Shi, JM; Liu, ZG; Shen, J; Zhu, YQ or concate me.. Name: Pyrazine-2-carboxylic acid
Reference:
Patent; Chevron Research Company; US4732894; (1988); A;,
Pyrazine – Wikipedia,
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