MoA Studies of the TEAD P-Site Binding Ligand MSC-4106 and Its Optimization to TEAD1-Selective Amide M3686.

Taking the structural information into account, we were able to tune the TEAD selectivity for a specific chemotype. However, different TEAD selectivity profiles did not affect the compound potency or efficacy in the NCI-H226 viability assay. Amides based on or analogues showed improved viability efficacy compared with the corresponding acids.

2024 ACLP Recommendations for Training Residents in Consultation-Liaison Psychiatry.

Background: Despite rapid shifts in consultation-liaison psychiatry (CLP) training in residency, including increasing general residency training requirements from the Accreditation Council for Graduate Medical Education, greater utilization of advanced practice providers, and effects of the coronavirus-2019 pandemic, the Academy of Consultation-Liaison Psychiatry has not updated recommendations for residency training in CLP since 2014. A national survey of residency program directors in 2021 suggested many changes to the structure of CLP rotations at individual programs over the past decade.

Objective: These recommendations are intended to guide residency program directors toward optimizing CLP training for all residents, including those who will eventually pursue CLP fellowship.

Discovery of reversible and covalent TEAD 1 selective inhibitors MSC-1254 and MSC-5046 based on one scaffold.

The Transcriptional Enhanced Associated Domain (TEAD) family of transcription factors are key components of the Hippo signalling family which play a crucial role in the regulation of cell proliferation, differentiation and apoptosis. The identification of inhibitors of the TEAD transcription factors are an attractive strategy for the development of novel anticancer therapies. A HTS campaign identified hit 1, which was optimised using structure-based drug design, to deliver potent TEAD1 selective inhibitors with both a reversible and covalent mode of inhibition.

Implementation of an Evidence-Based Treatment Protocol and Order Set for Alcohol Withdrawal Syndrome.

Background: Alcohol withdrawal syndrome (AWS) is highly prevalent in hospital inpatients. Recent evidence supports use of phenobarbital and gabapentin in certain patients, and screening tools for severe withdrawal risk can be used to guide care. Inpatients with AWS should also be considered for evidence-based treatment for alcohol use disorder (AUD).