Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast was written by Ochi, Kosuke;Suzawa, Ken;Thu, Yin Min;Takatsu, Fumiaki;Tsudaka, Shimpei;Zhu, Yidan;Nakata, Kentaro;Takeda, Tatsuaki;Shien, Kazuhiko;Yamamoto, Hiromasa;Okazaki, Mikio;Sugimoto, Seiichiro;Shien, Tadahiko;Okamoto, Yoshiharu;Tomida, Shuta;Toyooka, Shinichi. And the article was included in Cancer Science in 2022.Synthetic Route of C18H17NO5 This article mentions the following:
Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment that mediate resistance of cancer cells to anticancer drugs. Tranilast is an antiallergic drug that suppresses the release of cytokines from various inflammatory cells. In this study, we investigated the inhibitory effect of tranilast on the interactions between non-small cell lung cancer (NSCLC) cells and the CAFs in the tumor microenvironment. Three EGFR-mutant NSCLC cell lines, two KRAS-mutant cell lines, and three CAFs derived from NSCLC patients were used. To mimic the tumor microenvironment, the NSCLC cells were cocultured with the CAFs in vitro, and the mol. profiles and sensitivity to mol. targeted therapy were assessed. Crosstalk between NSCLC cells and CAFs induced multiple biol. effects on the NSCLC cells both in vivo and in vitro, including activation of the STAT3 signaling pathway, promotion of xenograft tumor growth, induction of epithelial-mesenchymal transition (EMT), and acquisition of resistance to mol.-targeted therapy, including EGFR-mutant NSCLC cells to osimertinib and of KRAS-mutant NSCLC cells to selumetinib. Treatment with tranilast led to inhibition of IL-6 secretion from the CAFs, which, in turn, resulted in inhibition of CAF-induced phospho-STAT3 upregulation. Tranilast also inhibited CAF-induced EMT in the NSCLC cells. Finally, combined administration of tranilast with mol.-targeted therapy reversed the CAF-mediated resistance of the NSCLC cells to the mol.-targeted drugs, both in vitro and in vivo. Our results showed that combined administration of tranilast with mol.-targeted therapy is a possible new treatment strategy to overcome drug resistance caused by cancer-CAF interaction. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8Synthetic Route of C18H17NO5).
2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8) belongs to amides. The solubilities of amides and esters are roughly comparable. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds. Tertiary amides, with the important exception of N,N-dimethylformamide, exhibit low solubility in water. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons. These hydrogen bonds are also have an important role in the secondary structure of proteins.Synthetic Route of C18H17NO5
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics