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While Polo-like kinase 1 (PLK1) inhibitors have shown promise in clinical settings for treating triple-negative breast cancer tumors and other solid tumors, they are limited by their ability to bind non-selectively to the ATP kinase domain. Therefore, we sought to develop a PLK1 allosteric inhibitor targeting the PLK1 T-loop (a switch responsible for activation) and evaluate its effects in triple-negative breast cancer cells. A novel compound, RK-10, was developed based on an in silico model, and its effects on specificity, viability, migration, and cell cycle regulation in MCF-10A and MDA-MB 231 cells were evaluated. When MDA-MB 231 cells were treated with 0–50 µg/mL RK-10, phospho-PLK1 (Thr-210) was decreased in cells cultured adherently and cells cultured as mammospheres. RK-10 significantly inhibited viability after 24 h; however, by 48 h, 25–50 µM RK-10 caused >50% reduction. RK-10 attenuated wound healing by up to 99.7% and caused S and G2/M cell cycle arrest, which was associated with increased p21 expression. We developed a novel allosteric inhibitor which mediates anti-proliferative and anti-migratory properties through targeting phospho-PLK1 (Thr-210) in mammospheres and causing S phase and G2/M cell cycle arrest. Further development of PLK1 allosteric inhibitors may be a promising approach for TNBC treatment. [ABSTRACT FROM AUTHOR]

Quercetin is an anti-oxidant agent, commonly used as an anti-inflammatory, anti-rheumatic, anti-diabetic, anti-ulcer, and is also used for the treatment of several cancers such as bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, prostate and others. In the present study, dispersible tablets of Quercetin, using three different disintegrants such as Crospovidone, Amberlite IR P 88 with different ratios, and complexatation done with Soluplus by Hot Melt Extrusion (HME) Method, was prepared and the solubility of Quercetin was increased. All formulations were studied in terms of pre-compressional parametres (flow properties) such as bulk density, tapped density, angle of repose, Carr's index and post compressional studies such as weight variation test, disintegration time, dispersion time, friability test, drug release and study. Optimized formulation F6 was evaluated for pharmacokinetics parametres, anticancer activities and stability studies as per ICH guidelines. [ABSTRACT FROM AUTHOR]