Development of an in vitro cholestatic drug-induced liver injury evaluation system using HepG2-hNTCP-C4 cells in sandwich configuration was written by Sakai, Yoko;Okumura, Hiroki;Iwao, Takahiro;Watashi, Koichi;Ito, Kousei;Matsunaga, Tamihide. And the article was included in Toxicology In Vitro in 2019.Application In Synthesis of 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid This article mentions the following:
Toxicol. approaches in screening drugs that cause drug-induced liver injury (DILI) are urgently needed to reduce the risk of developing DILI and avoid immense costs resulting from late-stage drug withdrawal from clin. trials. Cholestatic DILI is characterized by bile acid (BA) accumulation in hepatocytes, typically caused by drug-induced inhibition of important bile transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2/3/4 (MRP2/3/4). Therefore, NTCP expression is essential for construction of an in vitro hepatocellular toxicity evaluation system. Here, we investigated whether sandwich-cultured HepG2-hNTCP-C4 (SCHepG2-hNTCP-C4) cells were applicable for evaluation of cholestatic DILI. In SCHepG2-hNTCP-C4 cells, NTCP and MRP2/4 expression levels were comparable to those in human primary hepatocytes; however, BSEP expression was low. In addition, the substrates tauro-nor-THCA-24 DBD and CDF confirmed the functionality of NTCP and MRP2, resp. When 22 known hepatotoxins were exposed to BAs to evaluate cholestatic DILI, cytotoxicity in SCHepG2-hNTCP-C4 cells was more frequent than that in SCHepG2 cells. Thus, SCHepG2-hNTCP-C4 cells may be useful preclin. screening tools to predict the risk of cholestatic DILI induced by drug candidates. However, further studies are needed to determine why the cholestatic cytotoxicity of some compounds would be still insufficient in SCHepG2-hNTCP-C4 cells. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8Application In Synthesis of 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid).
2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8) belongs to amides. In primary and secondary amides, the presence of N–H dipoles allows amides to function as H-bond donors as well. Thus amides can participate in hydrogen bonding with water and other protic solvents; the oxygen atom can accept hydrogen bonds from water and the N–H hydrogen atoms can donate H-bonds. In simple aromatic amides, fragmentation occurs on both sides of the carbonyl group. If a hydrogen is available in N-substituted aromatic amides, it tends to migrate and form an aromatic amine and the loss of a ketene.Application In Synthesis of 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics