Loss of MK2 Enhances Radiation-Mediated Apoptosis in Bladder Cancer.

Background: Bladder cancer patients unable to receive cystectomy or who choose to pursue organ-sparing approach are managed with definitive (chemo)radiotherapy. However, this standard of care has not evolved in decades and disease recurrence and survival outcomes remain poor. Identifying novel therapies to combine with radiotherapy (RT) is therefore paramount to improve overall patient outcomes and survival.

Targeted Reversible Covalent Modification of a Noncatalytic Lysine of the Krev Interaction Trapped 1 Protein Enables Site-Directed Screening for Protein-Protein Interaction Inhibitors.

The covalent reversible modification of proteins is a validated strategy for the development of probes and candidate therapeutics. However, the covalent reversible targeting of noncatalytic lysines is particularly challenging. Herein, we characterize the 2-hydroxy-1-naphthaldehyde (HNA) fragment as a targeted covalent reversible ligand of a noncatalytic lysine (Lys) of the Krev interaction trapped 1 (KRIT1) protein.

Systematic review of the potential carcinogenicity of bisphenol A in humans.

Bisphenol A (BPA) is a synthetic chemical to which humans are exposed through a variety of environmental sources. We have conducted a comprehensive, systematic review of 29 epidemiology studies and 27 experimental animal studies, published through May 2022, evaluating the potential carcinogenicity of BPA to contribute to the understanding of whether BPA is carcinogenic in humans. We conducted this review according to best practices for systematic reviews and incorporating established frameworks for study quality evaluation and evidence integration.

A randomized, double-blind, placebo controlled, phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of LB-102, a selective dopamine D/5-HT inhibitor.

LB-102 is an N-methylated analogue of amisulpride under development to treat schizophrenia. LB-102 was evaluated in a Phase 1, double-blind, placebo-controlled, clinical study to evaluate safety and pharmacokinetics. This was a first-in-human study examining single and multiple doses of LB-102 administered orally in 64 healthy volunteers.