Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes. CoREST knockdown, gene expression, and ChIP studies suggest that corin’s favorable pharmacologic effects may rely on an intact CoREST complex. Corin was also effective in slowing tumor growth in a melanoma mouse xenograft model. These studies highlight the promise of a new class of two-pronged hybrid agents that may show preferential targeting of particular epigenetic regulatory complexes and offer unique therapeutic opportunities.

Psychotropic medications are commonly prescribed to school-aged youth for the management of mental health concerns. This paper describes the current state of evidence for psychotropic medications in school-aged youth. More specifically, the following sections summarize relevant medication research trials and practice parameters pertaining to psychotropic medication prescribing as well as the specific medications indicated for a range of commonly presenting disorders and symptom clusters in school-aged youth. For each of these disorders and symptom clusters, key findings pertaining to the current state of science and practice are highlighted for the purpose of offering patients, clinicians, researchers, and policymakers with nuanced considerations for the role of psychopharmacology within the context of a larger “whole-child” approach to care that relies on the collaboration of providers and services across systems of care to promote optimal child and family health and wellness. The paper concludes with a discussion about supporting the use of medication treatments in schools, including considerations for ensuring effective family-school-health system collaboration to best meet youth mental health needs.