Aldose reductase-IN-1 (AT-001, Caficrestat) is a highly potent inhibitor of aldose reductase with an IC50 value of 28.9 pM, which can target the relaxin hormone signaling pathway in prostate cancer models.

METHODS: To confirm that Aldose reductase-IN-1（ AT-001，Caficrestat） retains its ability to bind to the major relaxin receptor RXFP1, H2 relaxin was labeled with 125I using Pierce iodination reagent, which radioiodinates the phenol aromatic ring of the Tyr residue (Tyr3 on the A chain).
RESULTS In an in vitro cell assay using the 293T.RXFP1 cell line, we showed that H2 relaxin binds to RXFP1 in the presence of a cognate competitive RBA with a Kd of 17.0 nM; similarly, Aldose reductase-IN-1（ AT-001，Caficrestat） was shown to retain its binding ability to RXFP1 in the presence of a competitive RBA, inhibiting the binding of 125I-labeled H2 relaxin with a Ki of 9.2 μM[3].

METHODS: Male C57BL/6J mice (8 weeks old) were subjected to experimental type 2 diabetes/diabetic cardiomyopathy for 10 weeks. At 4 weeks, they were given a single intraperitoneal injection of streptozotocin (75 mg/kg). Animals were then randomly assigned to Aldose reductase-IN-1 (AT-001, Caficrestat) (40 mg/kg/day, intraperitoneal injection, for 3 weeks). At the completion of the study, hearts were perfused in an isolated working mode to assess energy metabolism.
RESULTS Aldose reductase-IN-1 (AT-001, Caficrestat) improved diastolic function and cardiac efficiency in mice with experimental type 2 diabetes; in mice with diabetic cardiomyopathy, Aldose reductase-IN-1 (AT-001, Caficrestat) also reduced cardiac fibrosis and hypertrophy. [1]