Pyrrolo[2,1-f][1,2,4]triazine: a promising fused heterocycle to target kinases in cancer therapy

Recent updates on 1,2,3‐, 1,2,4‐, and 1,3,5‐triazine hybrids (2017–present): The anticancer activity, structure–activity relationships, and mechanisms of action

“…Heterofused triazine hybrids including pyrrolo[2,1-c][1,2,4]triazine and pyrrolo[2,1-f] [1,2,4]triazine are potential inhibitors of carbonic anhydrase, cyclin-dependent kinase 2, tyrosinase, urease, thymidine phosphorylase, and tubulin. [18,19] The pyrrolo[2,1-f][1,2,4]triazine CYH33 (1, Figure 3, Table 1; half maximal inhibitory concentration/IC 50 : <1.0 µM, Sulforhodamine B/SRB assay), a selective phosphatidylinositol 3-kinase α (PI3Kα, IC 50 :5.9 nM) inhibitor, was highly potent against a panel of 21 cancer cell lines originated from lung, breast, ovary, colon, and prostate.…”

“…To date, several strategies have been developed to treat this deadly disease, mainly surgery, radiotherapy, immunotherapy, hormone therapy, and chemotherapy. [ 4 ] Clinically, chemotherapy is an optimal therapeutic approach for many cancers, and the Food and Drug Administration (FDA) approved more than 350 new drugs for cancer therapy from 2009 to 2018. [ 5,6 ] However, the major drawbacks of most available anticancer agents are the low specificity, obvious systemic toxicity and side effects, and easy‐to‐generate drug resistance, creating an urgent demand to develop novel anticancer chemotherapeutics.…”

“…[13,14] In particular, triazine hybrids have the potential to overcome drug resistance, enhance efficacy, improve specificity, and reduce side effects. Several triazine hybrids which are exemplified by avapritinib (pyrrolo[2,1-f][1,2,4]triazine, Figure 1), brivanib (pyrrolo[2,1-f][1,2,4]triazine), capmatinib (imidazo [1,2-b] [1,2,4]triazine), gedatolisib (1,3,5-triazineurea hybrid), and enasidenib (1,3,5-triazine-pyridine hybrid) are already in the market, demonstrating that rational design of triazine hybrids may provide novel anticancer chemotherapeutics. [15,16] This review outlines the latest signs of progress related to the anticancer potential of triazine hybrids, covering articles published from 2017 to the present.…”

Novel IRAK Degraders for Treating Cancer

“…For DC 50 , “A” means <0.01 μM, “B” means 0.01–0.1 μM, “C” means >0.1–0.2 μM, and “D” means >0.2 μM. …”

Selenium-Modified Chitosan Induces HepG2 Cell Apoptosis and Differential Protein Analysis

“…1,2 Modern studies have focused on developing novel chemotherapeutics to induce cancer-cell apoptosis with few side effects. [3][4][5] Apoptosis, a process of self-controlling suicide death, is mainly caused by intrinsic and extrinsic mechanisms. 6,7 External pathways involve ligand binding to activate death receptors and then trigger death-inducing signaling.…”