Olumacostat Glasaretil, a Promising Topical Sebum-Suppressing Agent that Affects All Major Pathogenic Factors of Acne Vulgaris  Bodo C. Melnik  Journal of Investigative Dermatology  Volume 137, Issue 7, Pages 1405-1408 (July 2017) DOI: 10.1016/j.jid.2017.01.026 Copyright © 2017 The Author Terms and Conditions

Figure 1 Schematic representation of the proposed olumacostat glasaretil (OG) mode of action in the pathogenesis of acne vulgaris. Puberty and the Western diet increase serum levels of IGF-1, which enhances androgen synthesis and formation of dihydrotestosterone (DHT) via activation of 5α-reductase (5αR). IGF-1, via activation of the kinase Akt, stimulates the kinase mTORC1. Furthermore, activated Akt inhibits FoxO1, a known repressor of the key lipogenic transcription factors SREBP1 and peroxisome proliferator-–activated receptor-γ (PPARγ). Androgen receptor (AR) signaling, which is also repressed by FoxO1, induces the expression of SREBP1. SREBP1 promotes the expression of acetyl coenzyme A carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis. SREBP1 also increases the expression of Δ6-desaturase (Δ6D) and stearoyl CoA desaturase (SCD), which generate the monounsaturated fatty acids sapienic acid (C16:1Δ6) and oleic acid (C18:1Δ9), respectively. The beige box summarizes the impact of sebum free fatty acids (FFA) on P. acnes biofilm formation, comedogenesis, and sebofollicular inflammation. Journal of Investigative Dermatology 2017 137, 1405-1408DOI: (10.1016/j.jid.2017.01.026) Copyright © 2017 The Author Terms and Conditions