Research update and opportunity of non-hormonal male contraception: Histone demethylase KDM5B-based targeting

Abstract

With the continued increase in global human population, diverse contraception approaches have become increasingly essential, including non-hormonal male contraception. Non-hormonal approaches to contraception are very convenient; however, such options are limited because data regarding the identification and characterization of tissue/cell-specific targets and appropriate small molecule candidate contraceptives are lacking. Based on in-silico studies of genomics, transcriptomics, and proteomics, performed by mining datasets in PubMed, we first reviewed testis-, epididymis-, and germline cell-specific genes/proteins, with the aim of presenting evidence that many of these could become 'druggable' targets for the development of non-hormonal male contraceptives in the future. Although many hurdles remain before the successful therapeutic use of non-hormonal contraceptive, to facilitate this approach, we describe here the changing perspectives on several potential non-hormonal contraceptives (e.g. small molecules, plant extracts, etc.) that are under development; continued effort may yield marketable products. Further, we highlight specific enzymes within the histone lysine demethylase subfamily that play a central role in germ line regulation. In particular, we focused on several prospective candidate small-molecules suggested to interact with the catalytic domain of histone lysine demethylase KDM5B, which is ubiquitously expressed in the testis/spermatozoa of both mice and human.

Keywords: 2,4-PDCA (CID: 10365); Adjudin (CID: 9819086); CPI-455 (CID: 78426698); GSK-J1 (CID: 56963315); GSK467 (CID: 90446507); Gamendazole (CID: 11212172); Histone demethylase; JQ1 (CID: 46907787); KB-R7943 (CID: 9823846); KDM5-C49 (CID: 86346639); KDM5-C70 (CID: 90094283); KH7 (CID: 6252811); Lonidamine (CID: 39562); Lupeol (CID: 259846); Male contraceptive; Non-hormonal; PBIT (CID: 11957662); Pristimerin (CID: 159516); SKF96365 (CID: 104955); SKI606 (CID: 5328940); Small-molecule; Spermatogenesis; Spermatozoa.