Discovery of 2-mercapto nicotinoyl glycine a new potent skin lightening agent with a proven clinical efficacy

P. Sextius, R. De Dormael, G. Lereaux, E. Warrick, D. Kerob, X. Marat, S. Diridollou

INTRODUCTION

Melanin production inhibitors currently marketed inhibit tyrosinase, the rate limiting enzyme in melanin synthesis process. Yet only few have demonstrated clinical efficacy while some present safety issues. Moreover, environmental respect is barely taken into consideration. Research on skin lightening agents considering efficacy, safety but also environmental respect is then of great importance to significantly improve marketed actives. For this purpose, a high-throughput screening test (HTS) evaluating melanin production on a large chemical diversity and in silico predictive methodology was then used to design original and performant chemical structures resulting in the discovery of 2-mercapto nicotinoyl glycine (2-MNG). Mechanism studies were conducted in tubo, in vitro, as well as in vivo showing a unique mode of action of 2-MNG consisting in conjugating with melanin precursors, avoiding their integration into growing eumelanin and pheomelanin.