Abstract
MM-129 is a novel inhibitor targeting BTK/PI3K/AKT/mTOR and PD-L1, as it possesses antitumor activity against colon cancer. To evaluate the safety profile of MM-129, we conducted a toxicity study using the zebrafish and rodent model. MM-129 was also assessed for pharmacokinetics features through an in vivo study on Wistar rats. The results revealed that MM-129 exhibited favorable pharmacokinetics with quick absorption and 68.6% of bioavailability after intraperitoneal administration. No serious adverse events were reported for the use of MM-129, confirming a favorable safety profile for this compound. It was not fatal and toxic to mice at an anticancer effective dose of 10 μmol/kg. At the end of 14 days of administering hematological and biochemical parameters, liver and renal functions were all at normal levels. No sublethal effects were either detected in zebrafish embryos treated with a concentration of 10 μM. MM-129 has the potential as a safe and well-tolerated anticancer formulation for future treatment of patients with colon cancer.
Funder
National Science Center, Poland
Reference62 articles.
1. Synthesis of 1,2,4-triazine derivatives as potential anti-anxiety and anti-inflammatory agents;Mullick;Acta Pol. Pharm.,2009
2. 1,2,4-Triazine Analogs as Novel Class of Therapeutic Agents
3. Synthesis and antimycobacterial activity of some 4H-1,2,4-triazin-5-one derivatives
4. An overview on the recent developments of 1,2,4-triazine derivatives as anticancer compounds
5. New pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
1. Roles of Rictor alterations in gastrointestinal tumors (Review);Oncology Reports;2024-01-04
2. Assessment of an Anticancer Effect of the Simultaneous Administration of MM-129 and Indoximod in the Colorectal Cancer Model;Cancers;2023-12-26
3. A 50-year systemic review of bioavailability application in Soil environmental criteria and risk assessment;Environmental Pollution;2023-10
4. Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery—In Vitro and In Silico Evaluation;International Journal of Molecular Sciences;2023-06-30
5. Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as Novel Potential Anticancer Agents: Apoptosis, Oxidative Stress, and Cell Cycle Analysis;International Journal of Molecular Sciences;2023-05-09