Selective Inhibitor of Aldo-Keto Reductase family member 1B10 (AKR1B10) HCCFA | Funakoshi

Selective Inhibitor of AKR1B10
HCCFA

HCCFA is a potent and selective Inhibitor of Aldo-Keto Reductase family member 1B10 (AKR1B10).
AKR1B10 is a NADPH dependent reductase, and involved in metabolism of retinoid and isoprenoid.
After high expression of AKR1B10 in non-small cell lung cancer (NSCLC) was reported in 2005, such high expression was also found liver cancer, uterus cancer and bile duct cancer.
Therefore, AKR1B10 inhibitor was noted as a new target of anti-cancer drug development.

AKR1B10 shows 70.6% homology in amino-acid sequence to aldose reductase (AKR1B1, or AR), and both have similar structure and substrate specificity.
As a result, conventional inhibitors for AKR1B10 also inhibit AR to the same degree, selective inhibtor against AKR1B10 or AR has been searched.

HCCFA is a new compound which inhibits AKR1B10 selectively and strongly.

This product has been commercialized with the support of both the University of Toyama and Gifu Pharmaceutical University.

Fig.1 Inhibitory activity of HCCFA was measured by using recombinant AKR1B10 or AR. Data shows HCCFA inhibits AKR1B10 strongly and selectively.

Fig.2 A549 cells or CDDP-R-A549 cells (cisplatin-resistant A549 cells) were treated with 0 to 40 μM of HCCFA for 2 hours and cultured for 24 hours under culture media containing CDDP (cisplatin) 40 μM.
Data shows that HCCFA recovers CDDP susceptibility of CDDP-R-A549 cells in a dose-dependent manner.

Fig.3 Luciferase transduced A549-Luc cells were cultured in DMSO (control) or 20 μM HCCFA containing medium for 24 hours, and transfered to BALB/c nude mouse by tail vein injection.
4 days after, luminescent in lung was observed. Data shows that HCCFA inhibits proliferation and metastasis of A549 cells in vivo.

Endo S., et al., J. Med. Chem., 60:8441-8455 (2017).