Overview of all-trans-retinoic acid (ATRA) and its analogues: Structures, activities, and mechanisms in acute promyelocytic leukaemia.

All-trans-retinoic acid (ATRA) is effective for preventing cancer and treating skin diseases and acute promyelocytic leukaemia (APL). These pharmacological effects of ATRA are mainly mediated by retinoid X receptors (RXRs) and retinoic acid receptors (RARs). This article provides a comprehensive overview of the clinical progress on and the molecular mechanisms of ATRA in the treatment of APL. ATRA can promote the transcriptional activation of differentiation-related genes and regulate autophagy by inhibiting mTOR, which results in anti-APL effects. In detail, the structures, pharmacological effects, and clinical studies of 68 types of ATRA analogues are described. These compounds have excellent antitumour therapeutic potential and could be used as lead compounds for further development and research. [Display omitted] • This review discusses the structures, pharmacological activities, and relevant clinical trials of ATRA and its 68 analogues. • Two isomers of ATRA are introduced in detail, and the crystal structure of 9- cis -RA binding to RXRα is fully described. • In APL treatment, ATRA restores transcriptional activity to ensure normal differentiation by inducing PML-RARα fusion gene. • ATRA promotes autophagy by inhibiting the mTOR pathway, which inhibits unlimited leukaemic cells proliferation. [ABSTRACT FROM AUTHOR]