QSP modeling of a transiently inactivating antibody-drug conjugate highlights benefit of short antibody half life.

Antibody drug conjugates (ADC) are a promising class of oncology therapeutics consisting of an antibody conjugated to a payload via a linker. DYP688 is a novel ADC comprising of a signaling protein inhibitor payload (FR900359) that undergoes unique on-antibody inactivation in plasma, resulting in complex pharmacology. To assess the impact of FR inactivation on DYP688 pharmacology and clinical developability, we performed translational modeling of preclinical PK and tumor growth inhibition (TGI) data, accompanied by mechanistic Krogh cylinder tumor modeling.

Music-Based Therapy for the Treatment of Perioperative Anxiety and Pain-A Randomized, Prospective Clinical Trial.

: Music-based intervention has been advocated as a nonpharmacologic approach for the perioperative control of pain and anxiety in surgical patients. However, its impact on patients with preoperative anxiety has not been clearly established. Our study aimed to examine the impact of music-based intervention administered before, during, and after surgery on postoperative opioid consumption and pain levels, as well as preoperative anxiety, depression, and pain catastrophizing.

CHD1L Regulates Cell Survival in Breast Cancer and Its Inhibition by OTI-611 Impedes the DNA Damage Response and Induces PARthanatos.

The Chromodomain helicase DNA-binding protein 1-like (CHD1L) is a nucleosome remodeling enzyme, which plays a key role in chromatin relaxation during the DNA damage response. Genome editing has shown that deletion of CHD1L sensitizes cells to PARPi, but the effect of its pharmacological inhibition has not been defined. Triple-negative breast cancer SUM149PT, HCC1937, and MDA-MB-231 cells were used to assess the mechanism of action of the CHD1Li OTI-611.