jte-013 has been researched along with Colorectal-Neoplasms* in 2 studies
2 other study(ies) available for jte-013 and Colorectal-Neoplasms
| Article | Year |
|---|---|
Design, synthesis and biological evaluation of sphingosine-1-phosphate receptor 2 antagonists as potent 5-FU-resistance reversal agents for the treatment of colorectal cancer.
5-Fluorouracil (5-FU) and its prodrugs are the essential clinical drugs for colorectal cancer (CRC) treatment. However, the drug resistance of 5-FU has caused high mortality of CRC patients. Thus, it is urgent to develop reversal agents of 5-FU resistance. Sphingosine-1-phosphate receptor 2 (S1PR2) was proved to be a potential target for reversing 5-FU resistance, but the activity of known S1PR2 antagonists JTE-013 were weak in 5-FU-resistant cell lines. To develop more potent S1PR2 antagonists to treat 5-FU-resistant cancer, a series of JTE-013 derivatives were designed and synthesized. The most promising compound 40 could markedly reverse the resistance in 5-FU-resistant HCT116 cells and 5-FU-resistant SW620 cells via inhibiting the expression of dihydropyrimidine dehydrogenase (DPD). The key was that compound 40 with improved pharmacokinetic properties significantly increased the inhibitory rate of 5-FU in the SW620/5-FU cells xenograft model with no observable toxicity by inhibiting the expression of DPD in tumor and liver tissues. Altogether, these results suggest that compound 40 may be a promising drug candidate to reverse 5-FU resistance in the treatment of CRC. Topics: Antineoplastic Agents; Cell Proliferation; Cell Survival; Cells, Cultured; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Design; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Fluorouracil; Humans; Molecular Structure; Sphingosine-1-Phosphate Receptors; Structure-Activity Relationship | 2021 |
S1PR2 inhibitors potently reverse 5-FU resistance by downregulating DPD expression in colorectal cancer.
In this study, S1PR2 was reckoned as a brand-new GPCR target for designing inhibitors to reverse 5-FU resistance. Herein a series of pyrrolidine pyrazoles as the S1PR2 inhibitors were designed, synthesized and evaluated for their activities of anti-FU-resistance. Among them, the most promising compound JTE-013, exhibited excellent inhibition on DPD expression and potent anti-FU-resistance activity in various human cancer cell lines, along with the in vivo HCT116 Topics: Animals; Antimetabolites, Antineoplastic; Cell Line, Tumor; Colorectal Neoplasms; Dihydrouracil Dehydrogenase (NADP); Down-Regulation; Drug Resistance, Neoplasm; Fluorouracil; Humans; Mice, Nude; Molecular Docking Simulation; Pyrazoles; Pyridines; Sphingosine-1-Phosphate Receptors | 2020 |