Aldo-keto reductase 1C3-Assessment as a new target for the treatment of endometriosis

Abstract

Endometriosis is a common gynecological disorder, which is treated surgically and/ or pharmacologically with an unmet clinical need for new therapeutics. A completed phase I trial and a recent phase II trial that investigated the steroidal aldo-keto reductase 1C3 (AKR1C3) inhibitor BAY1128688 in endometriosis patients prompted this critical assessment on the role of AKR1C3 in endometriosis. This review includes an introduction to endometriosis with emphasis on the roles of prostaglandins and progesterone in its pathophysiology. This is followed by an overview of the major enzymatic activities and physiological functions of AKR1C3 and of the data published to date on the expression of AKR1C3 in endometriosis at the mRNA and protein levels. The review concludes with the rationale for using AKR1C3 inhibitors, a discussion of the effects of AKR1C3 inhibition on the pathophysiology of endometriosis and a brief overview of other drugs under clinical investigation for this indication.

Keywords: 9-cis-retinoic acid; 9α,11β-prostaglandin F(2); Androgens; Diclofenac (PubChem CID: 3033); Doxorubicin (PubChem CID: 31703); Dydrogesterone (PubChem CID: 9051); Flufenamic acid (PubChem CID: 3371); Geranylgeranial; Goserelin (PubChem CID: 5311128); Indomethacin (PubChem CID: 3715); Levonorgestrel (PubChem CID: 13109); Medroxyprogesterone acetate (PubChem CID: 6279); Mefenamic acid (PubChem CID: 4044); Naproxen (PubChem CID: 156391); Progesterone; Prostaglandin F(2α).