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.

Adult Height Following Prepubertal Treatment With Antiandrogen, Aromatase Inhibitor, and Reduced Hydrocortisone in CAH.

Context: Height outcome in patients with classic congenital adrenal hyperplasia (CAH) is suboptimal due to glucocorticoid and androgen excess.

Methods: In an open, randomized, controlled trial, children with classic CAH were randomized to receive a combination regimen of antiandrogen, aromatase inhibitor, reduced hydrocortisone, and fludrocortisone prior to puberty or standard therapy (hydrocortisone, fludrocortisone). Females continued on antiandrogen during puberty.

The Role of Goal Source in Escalation of Commitment.

Escalation of commitment is an important decision problem that occurs across different decision contexts. Recognizing that escalation involves one's effort to achieve some form of a goal, researchers have attempted to understand escalation of commitment as a goal-pursuing activity. Prior research works have suggested that escalation situations consist of (1) an initial goal setting phase and (2) an escalation decision-making phase and have investigated how goal difficulty and goal specificity influence escalation decisions.