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Abstract: Peroxisome Proliferator-Activated Receptor γ (PPARγ) activators have drawn great recent attention in the clinical management of type 2 diabetes mellitus, prompting several attempts to discover and optimize new PPARγ activators. With this in mind, we explored the pharmacophoric space of PPARγ using seven diverse sets of activators. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing self-consistent and predictive quantitative structure–activity relationship (QSAR) (r2 71 =0.80, F=270.3, r2 LOO =0.73, r2 PRESS against 17 external test inhibitors=0.67). Three orthogonal pharmacophores emerged in the QSAR equation and were validated by receiver operating characteristic (ROC) curves analysis. The models were then used to screen the national cancer institute (NCI) list of compounds. The highest-ranking hits were tested in vitro. The most potent hits illustrated EC50 values of 15 and 224nM. [Copyright &y& Elsevier]

P2Y 12 is a platelet surface protein which is responsible for the amplification of P2Y 1 response. It plays a crucial role in platelet aggregation and thrombus formation through an ADP-induced platelet activation mechanism. Despite that P2Y 12 platelets' receptor is an excellent target for developing antiplatelet agents, only five approved medications are currently in clinical use which are classified into thienopyridines and nucleoside-nucleotide derivatives. In the past years, many attempts for developing new candidates as P2Y 12 inhibitors have been made. This review highlights the importance and the role of P2Y 12 receptor as part of the coagulation cascade, its reported congenital defects, and the type of assays which are used to verify and measure its activity. Furthermore, an overview is given of the clinically approved medications, the potential naturally isolated inhibitors, and the synthesised candidates which were tested either in-vitro , in-vivo and/or clinically. Finally, we outline the in-silico attempts which were carried out using virtual screening, molecular docking and dynamics simulations in efforts of designing novel P2Y 12 antagonists. Various phytochemical classes might be considered as a corner stone for the discovery of novel P2Y 12 inhibitors, whereas a wide range of ring systems can be deliberated as leading scaffolds in that area synthetically and theoretically. [Display omitted] • The structure and function of P2Y 12 receptor. • Natural antagonists of P2Y 12 belong to different chemical groups such as stilbenoids, flavinolignans, benzofurans, terpenoids, alkaloids & ginsenosides. • Various oxazole, nicotinate, morpholine, adenosine-based, and cinnamic and ferulic acid derivatives among some other heterocyclic systems have shown divers biological activities. • Several Molecular modelling studies that lead to the discovery of novel P2Y 12 antagonists. [ABSTRACT FROM AUTHOR]

In recent decades, there has been a significant amount of research into breast cancer, with some important breakthroughs in the treatment of both primary and metastatic breast cancers. It's a well-known fact that treating breast cancer is still a challenging endeavour even though physicians have a fantastic toolset of the latest treatment options at their disposal. Due to limitations of current clinical treatment options, traditional chemotherapeutic drugs, and surgical options are still required to address this condition. In recent years, there have been several developments resulting in a wide range of treatment options. This review article discusses the cellular and molecular foundation of chemotherapeutic drugs, endocrine system-based treatments, biological therapies, gene therapy, and innovative techniques for treating breast cancer. [Display omitted] [ABSTRACT FROM AUTHOR]