FIDAS-5 is a potent and orally active methionine S-adenosyltransferase 2A (MAT2A) inhibitor with an IC50 of 2.1 μM. FIDAS-5 effectively competes against S-adenosylmethionine (SAM) for MAT2A binding. FIDAS-5 has anticancer activities[1].
Methionine adenosyltransferases (MATs) are essential enzymes for life as they produce S-adenosylmethionine (SAMe), the biological methyl donor required for a plethora of reactions within the cell[1].
S-adenosylmethionine (SAM) is a central metabolite since it is used as a methyl group donor in many different biochemical reactions[2]. Induction of MAT2A/MAT2B confers growth and survival advantage to cancerous cells, enhancing tumor migration[3]. FIDAS-5 is a potent and orally active methionine S-adenosyltransferase 2A (MAT2A) inhibitor with an IC50 of 2.1 μM. It effectively competes against S-adenosylmethionine (SAM) for MAT2A binding. FIDAS-5 shows anticancer activities. It induces the expression of p21WAF1/CIP1, a cell cycle inhibitor， after 36-hour treatment at 3 μM with both reduced level of SAM and SAH observed in LS174T cells. 7-day treatment with FIDAS-5 at 3 μM significantly inhibits the proliferation of LS174T cells, accompanied with reduced expression of c-Myc and cyclinD1. The liver SAM levels are significantly reduced in mice treated with FIDAS-5 at dose of 20 mg/kg for 1 week. Treatment with FIDAS-5 at 20 mg/kg, p.o., daily, for 2 weeks, significantly inhibits the growth of xenograft tumors of athymic nude mice, without obvious difference in body weight[4].
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