{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:37Z","timestamp":1787027737574,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T00:00:00Z","timestamp":1624665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center, Poland","award":["2018\/31\/B\/NZ7\/00875"],"award-info":[{"award-number":["2018\/31\/B\/NZ7\/00875"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2014MM-129, may act as a chemosensitizer, overcoming chemoresistance against 5-FU, the first-line agent in the chemotherapy of colon cancer.<\/jats:p>","DOI":"10.3390\/cancers13133203","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T22:24:57Z","timestamp":1624832697000},"page":"3203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["MM-129 as a Novel Inhibitor Targeting PI3K\/AKT\/mTOR and PD-L1 in Colorectal Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-4244","authenticated-orcid":false,"given":"Justyna Magdalena","family":"Hermanowicz","sequence":"first","affiliation":[{"name":"Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"},{"name":"Department of Clinical Pharmacy, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2254-7982","authenticated-orcid":false,"given":"Krystyna","family":"Pawlak","sequence":"additional","affiliation":[{"name":"Department of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8384-7116","authenticated-orcid":false,"given":"Beata","family":"Sieklucka","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7148-6111","authenticated-orcid":false,"given":"Robert","family":"Czarnomysy","sequence":"additional","affiliation":[{"name":"Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-9912","authenticated-orcid":false,"given":"Iwona","family":"Kwiatkowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kazberuk","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-873X","authenticated-orcid":false,"given":"Arkadiusz","family":"Surazynski","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9884-6068","authenticated-orcid":false,"given":"Mariusz","family":"Mojzych","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3751-0608","authenticated-orcid":false,"given":"Dariusz","family":"Pawlak","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,26]]},"reference":[{"key":"ref_1","first-page":"174","article-title":"A review on synthesis and biological activity of heterocyclic compounds bearing 1, 3, 5-triazine lead moiety","volume":"1","author":"Basedia","year":"2011","journal-title":"Am. 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