Discovery, synthesis and biological evaluation of a series of N-(phenylcarbamothioyl)-2-napthamides as inhibitors of Claudin-1.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, despite advancements in diagnosis. The main reason for this is that many newly diagnosed CRC patients will suffer from metastasis to other organs. Thus, the development of new therapies is of critical importance. Claudin-1 protein is a component of tight junctions in epithelial cells, including those found in the lining of the colon. It plays a critical role in the formation and maintenance of tight junctions, which are essential for regulating the passage of molecules between cells. In CRC, claudin-1 is often overexpressed, leading to an increase in cell adhesion, which can contribute to the development and progression of the disease. Studies show that high levels of claudin-1 are associated with poor prognosis in CRC patients and targeting claudin-1 may have therapeutic potential for the treatment of CRC. Previously, we have identified a small molecule that inhibits claudin-1 dependent CRC progression. Reported herein are our lead optimization efforts around this scaffold to identify the key SAR components and the discovery of a key new compound that exhibits enhanced potency in SW620 cells.

Relationship Between Physical Fitness and the Physical Demands of 50-Over Cricket in Fast Bowlers.

ABSTRACT: Webster, TM, Comfort, P, and Jones, PA. Relationship between physical fitness and the physical demands of 50-over cricket in fast bowlers. J Strength Cond Res 36(3): e66-e72, 2022-Professional cricket is constantly evolving and resulting in increased physiological demand placed on players. Fast bowlers experience the greatest physical demand during match-play; despite this, research has overlooked the importance of specific physical attributes to optimizing physical match performance. The aim of this study was to investigate the relationships between 50-Over physical match performance and tests of physical qualities in fast bowlers. Fifteen professional male fast bowlers (age = 23.8 ± 4.0 years; height = 183.4 ± 6.7 cm; body mass = 82.9 ± 9.2 kg) participated in the study. Subjects completed the following physical fitness tests; sum of skinfolds, countermovement jump (CMJ), 20-m sprint, and the Yo-Yo intermittent recovery test level 1. Global positioning system data were collected during 6 professional 50-Over fixtures. Moderate correlations were established between CMJ height to total distance covered (r = 0.585; p = 0.022), sprinting distance (ρ = 0.554; p = 0.032), and maximal velocity (r = 0.567; p = 0.027); 20-m sprint time to total distance covered (ρ = -0.519; p = 0.047) and PlayerLoad (ρ = -0.561; p = 0.03); and Yo-Yo distance to total match distance (r = 0.520; p = 0.047) and sprinting distance (ρ = 0.524; p = 0.045). These findings demonstrate the predictive importance of prolonged intermittent running ability, jump, and sprint performance to match running performance of elite fast bowlers in 1-day cricket. Strength and conditioning coaches should use such information to design training to ensure fast bowlers are adequately conditioned to meet the demands of match running performance.