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.

Introduction:The prevalence of behavioral health disorders in children is approximately 15%-20%, yet less than half of the children ever receive treatment for these conditions. The lack of access to behavioral health care is common in urban areas but even more difficult to access in rural areas. Screening for behavioral health in a primary care setting is one of the first strategies to reduce this problem and improve access to care. The primary goal of this study was to examine behavioral health screening practices of pediatric primary care providers in a rural midwestern state. Method: A survey that queried family practice/internal medicine and pediatric providers who provide care to pediatric patients was delivered to over 300 primary care providers across the state. The number of surveys returned was 112. Results: The Modified Checklist for Autism tool was administered by 80% of pediatric providers and 30% of family practice primary care providers. The Patient Health Questionnaire for depression was administered by 72% of pediatric and 80% of family practice providers. Most of the primary care providers had a behavioral health provider present in the clinic, which likely resulted in higher screening rates compared to the national average. Discussion: The screening practices of the family practice and pediatric subspecialities reflect their respective current professional organization recommendations. Although most providers believe it is important to screen for developmental and behavioral disorders, further system changes are