2-pyridone derivative 9b

2-pyridone derivative 9b is a synthetic small molecule belonging to the class of spiro[indene-2,4′-pyridine] compounds. It acts as a dual inhibitor of human dihydrofolate reductase (h-DHFR) and epidermal growth factor receptor tyrosine kinase (EGFR TK). In preclinical studies, compound 9b demonstrated potent anti-proliferative activity against HepG-2 (hepatocellular carcinoma) and Caco-2 (colorectal carcinoma) cell lines with IC50 values of approximately 6.89 µM and 5.68 µM, respectively. The compound induces apoptosis by halting the cell cycle at the G1/S phase, upregulating BAX, and downregulating Bcl-2 expression in cancer cells. It also exhibits immunomodulatory effects by inhibiting TNF-alpha and IL-6 production more potently than lapatinib in vitro. Mechanistically, it inhibits h-DHFR with an IC50 comparable to methotrexate (~0.19 µM), and EGFR with an IC50 close to that of lapatinib (~0.11 µM). In silico predictions suggest it may inhibit CYP2C9 and CYP3A4 enzymes[1][3][4].

Other names

spiro[indene-2,4′-pyridine] derivative 9b