Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor

Since the first characterization of the 5-hydroxytryptamine 2B receptor (5-HT2BR) in 1992, significant progress has been made in 5-HT2BR research. Herein, we summarize the biological function, structure, and small-molecule pharmaceutical ligands of the 5-HT2BR. Emerging evidence has suggested that the 5-HT2BR is implicated in the regulation of the cardiovascular system, fibrosis disorders, cancer, the gastrointestinal (GI) tract, and the nervous system. Eight crystal complex structures of the 5-HT2BR bound with different ligands provided great insights into ligand recognition, activation mechanism, and biased signaling. Numerous 5-HT2BR antagonists have been discovered and developed, and several of them have advanced to clinical trials. It is expected that the novel 5-HT2BR antagonists with high potency and selectivity will lead to the development of first-in-class drugs in various therapeutic areas.

Crystal structure and Hirshfeld surface analysis of dichlorido(methanol-κO)bis(2-methylpyridine-κN)copper(II)

In the title complex, [CuCl2(C6H7N)2(CH3OH)], the copper atom is five-coordinated by two nitrogen atoms of 2-methylpyridine ligands, two chloro ligands and an oxygen atom of the methanol molecule, being in a tetragonal–pyramidal environment with N and Cl atoms forming the basal plane. In the crystal, complex molecules related by the twofold rotation axis are joined into dimeric units by pairs of O—H...Cl hydrogen bonds. These dimeric units are assembled through C—H...Cl interactions into layers parallel to (001).

Ligand based 3D-QSAR pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors

Background The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer.Methods The known inhibitors were collected to construct 3D-QSAR pharmacophore model, which was verified by cost analysis, test set validation and Fischer test. Virtual screening of zinc database based on pharmacophore was carried out. FGFR1 crystal complex was downloaded from the protein database to dock with the compound. Finally, the absorption, distribution, metabolism and excretion (ADME) characteristics and toxicity of a series of potential inhibitors were studied.Results It was found that the constructed pharmacophore had a good ability to predict the activity. 2763 compounds in the database could hit well and the predicted activity value was less than 1 µM. Through molecular docking, we found that six compounds can bind to protein stably and inhibit the activity of FGFR1 through hydrogen bond interaction. In ADME and toxicity studies, we have successfully screened out a compound with a new structure scaffold, and found that it has good oral bioavailability and non-toxic.Conclusions This study screened out a new potential drug for cancer treatment, which can be further studied to explore its better therapeutic effect.