compound 10g

Compound 10g is a synthetic 1-phenylpyrazolo[3,4-d]pyrimidine analogue conjugated with an amino acid, developed as a potent inhibitor of human dihydrofolate reductase (hDHFR). In preclinical research, it demonstrated significant enzymatic inhibition with an IC50 value below 1 µM, showing higher potency than the standard antifolate methotrexate (MTX). The compound exhibits broad-spectrum in vitro cytotoxic activity against several methotrexate-resistant human cancer cell lines, including those derived from the prostate, pancreas, colon, liver, cervix, and breast. Its mechanism involves binding to the hDHFR active site, thereby disrupting folate metabolism and inhibiting the growth of malignant cells.