Abstract
Background and aims: The purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer. Methods: MM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice. The mechanistic studies investigated cellular affinity of a new 1,2,4-triazine derivative by measuring levels of intracellular/extracellular signal molecules participating in tumorigenesis. Results: The results revealed that MM-129 significantly reduced tumor growth in mice challenged with DLD-1 and HT-29 cells. It exerted the ability to inhibit intracellular molecules promoting tumorigenesis and inducing cell cycle arrest, like Akt, mTOR, and CDK2. Simultaneously, it was able to downregulate PD-L1 expression, which involves immunological self-tolerance. Combined administration of MM-129 and 5-fluorouracil (5-FU) additionally amplified these effects, which were manifest as an increase population of cells in the G0/G1 phase. Conclusions: A novel 1,2,4-triazine derivative with a dual mechanism of antitumor activity—MM-129, may act as a chemosensitizer, overcoming chemoresistance against 5-FU, the first-line agent in the chemotherapy of colon cancer.
Funder
National Science Center, Poland
Reference54 articles.
1. A review on synthesis and biological activity of heterocyclic compounds bearing 1, 3, 5-triazine lead moiety;Basedia;Am. J. Pharm. Tech. Res.,2011
2. Synthesis, crystal structure and anticancer activity of novel derivatives of ethyl 1-(4-oxo-8-aryl-4,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)formate
3. Antifungal activity, SAR and physicochemical correlation of some thiazole-1,3,5-triazine derivatives
4. Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket
5. Synthesis and analgesic-anti-inflammatory activities of some 1,2,4-triazine derivatives;Makhlouf;Arzneimittelforschung,2004
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