AKR1C3 inhibitors and exploiters for the treatment and therapeutic monitoring of cancer: a patent review (2020-present).

INTRODUCTION

Aldo-keto reductase 1C3 (AKR1C3) is a drug target for the treatment of various androgen‑dependent malignancies, including castration-resistant prostate cancer as well as hematological cancers. The enzyme plays a key role in the conversion of androgen precursors into potent androgen receptor ligands and the conversion of prostaglandins from pro-differential to pro-proliferative, thereby facilitating the progression of these malignancies. Additionally, AKR1C3 plays a role in chemotherapy resistance, reducing therapeutics to inactive forms and stabilizing the expression of mutant androgen receptors.

AREA COVERED: This article reviews patents published since 2020, obtained from WIPO and SciFinder, covering AKR1C3 inhibitors, compounds that exploit AKR1C3 for prodrug activation, and the use of AKR1C3 expression levels as a biomarker for measuring disease and therapeutic response. In addition to inhibitors, this article reviews the first reported AKR1C3/AR-v7 dual degrader.

EXPERT OPINION: Multiple compounds have been reported to potently and selectively inhibit AKR1C3, eliciting tumor growth inhibition as standalone agents and when used in combination with clinically approved chemotherapeutics. With drug resistance an ever-present issue, exploration of alternative routes for treating malignancies via AKR1C3 targeting offers tremendous potential. Translation to clinical trials and their effect in patients is expected to be revealed in the coming years.