Drug repurposing screening identifies tioconazole as an ATG4 inhibitor that suppresses autophagy and sensitizes cancer cells to chemotherapy was written by Liu, Pei-Feng;Tsai, Kun-Lin;Hsu, Chien-Jen;Tsai, Wei-Lun;Cheng, Jin-Shiung;Chang, Hsueh-Wei;Shiau, Chung-Wai;Goan, Yih-Gang;Tseng, Ho-Hsing;Wu, Chih-Hsuan;Reed, John C.;Yang, Lee-Wei;Shu, Chih-Wen. And the article was included in Theranostics in 2018.Application of 53902-12-8 This article mentions the following:
Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy. However, this theory in clin. cancer research remains controversial due to the limited number of drugs that specifically inhibit autophagy-related (ATG) proteins. We screened FDA-approved drugs using a novel platform that integrates computational docking and simulations as well as biochem. and cellular reporter assays to identify potential drugs that inhibit autophagy-required cysteine proteases of the ATG4 family. The effects of ATG4 inhibitors on autophagy and tumor suppression were examined using cell culture and a tumor xenograft mouse model. Tioconazole was found to inhibit activities of ATG4A and ATG4B with an IC50 of 1.3μM and 1.8μM, resp. Further studies based on docking and mol. dynamics (MD) simulations supported that tioconazole can stably occupy the active site of ATG4 in its open form and transiently interact with the allosteric regulation site in LC3, which explained the exptl. observed obstruction of substrate binding and reduced autophagic flux in cells in the presence of tioconazole. Moreover, tioconazole diminished tumor cell viability and sensitized cancer cells to autophagy-inducing conditions, including starvation and treatment with chemotherapeutic agents. Tioconazole inhibited ATG4 and autophagy to enhance chemotherapeutic drug-induced cytotoxicity in cancer cell culture and tumor xenografts. These results suggest that the antifungal drug tioconazole might be repositioned as an anticancer drug or chemosensitizer. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8Application of 53902-12-8).
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.Application of 53902-12-8
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics