Acitretin (Ro 10-1670) is a second-generation, systemic retinoid that has been used in the treatment of psoriasis.

Acitretin stimulates ADAM10 promoter activity with an EC(50) of 1.5 mM and leads to an increase of mature ADAM10 protein that results in a two- to three-fold increase of the ratio between alpha- and beta-secretase activity in neuroblastoma cells. [1] Acitretin (5-20 μM) impairs mitochondrial phosphorylation efficiency as demonstrated by the decrease in the state 3 respiration and ATP levels, and by the increase in the lag phase of ADP phosphorylation cycle, without affecting the membrane potential. Acitretin induces Ca(2+)-mediated mitochondrial permeability transition (MPT) and decreased the adenine nucleotide translocase (ANT) content. [2] Acitretin preferentially inhibits the growth of SCL-1 cells in a dose- and time-dependent manner, but not of non-malignant keratinocyte HaCaT cells. Acitretin increases the levels of CD95 (Fas), CD95-ligand and Fas-associated death domain. Acitretin is able to induce apoptosis in skin cancer cells possibly via death receptor CD95 apoptosis pathway without affecting the viability of normal keratinocyte. [3]

Acitretin undergoes alpha-oxidation, chain shortening O-demethylation, and glucuronidation in the perfused rat liver. [4] Acitretin rapidly appears in liver and muscle of rats, where it undergoes redistribution into skin and adipose tissue. [5]