Design, synthesis and biological evaluation of nitric oxide-releasing 5-cyano-6-phenyl-2, 4-disubstituted pyrimidine derivatives.

In this study, a series of nitric oxide (NO) -releasing 5-cyano-6-phenyl-2, 4-disubstituted pyrimidine derivatives were designed and synthesized. In the in vitro biological evaluation, compound 24l exhibited optimal antiproliferative activity against MGC-803 cells with the IC value of 0.95 µM, significantly better than that of the positive control 5-FU.

Annual review of KRAS inhibitors in 2022.

Kirsten rat sarcoma viral (KRAS) oncogene is the most commonly mutated isoform of RAS, accounting for 85% of RAS-driven human cancers. KRAS functioning as a signaling hub participates in multiple cellular signaling pathways and regulates a variety of critical processes such as cell proliferation, differentiation, growth, metabolism and migration. Over the past decades, KRAS oncoprotein has been considered as an "undruggable" target due to its smooth surface and high GTP/GDP affinity.

The overview of Mitogen-activated extracellular signal-regulated kinase (MEK)-based dual inhibitor in the treatment of cancers.

Mitogen-activated extracellular signal-regulated kinase 1 and 2 (MEK1/2) are the critical components of the mitogen-activated protein kinase/extracellular signal-regulated kinase 1 and 2 (MAPK/ERK1/2) signaling pathway which is one of the well-characterized kinase cascades regulating cell proliferation, differentiation, growth, metabolism, survival and mobility both in normal and cancer cells. The aberrant activation of MAPK/ERK1/2 pathway is a hallmark of numerous human cancers, therefore targeting the components of this pathway to inhibit its dysregulation is a promising strategy for cancer treatment. Enormous efforts have been done in the development of MEK1/2 inhibitors and encouraging advancements have been made, including four inhibitors approved for clinical use.