KOTX1 (MBE1) is a potent, selective and reversible ALDH1A3 inhibitor with IC50 of 5.14 nM by Aldefluor assay in A375 cells.
KOTX1 does not inhibit the closely related ALDH1A1 or ALDH2 isoforms.
KOTX1 (40 mg/kg/day, oral gavage, 1 week) inhibits ALDH1A3 activity and restores β-cell function and maturity in db/db mice.
KOTX1 IC50 is 10-fold lower in human A375 cells than in diabetic mouse islets.
KOTX1 (40 mg/kg/day, oral gavage) improved glucose control, increased insulin secretion, and enhanced glucose tolerance in male DIO mice.
