Sulfonyl-containing phenyl-pyrrolyl pentane analogues: Novel non-secosteroidal vitamin D receptor modulators with favorable physicochemical properties, pharmacokinetic properties and anti-tumor activity.

Modulating the vitamin D receptor (VDR) is an effective way to treat for cancer. We previously reported a potent non-secosteroidal VDR modulator (sw-22) with modest anti-tumor activity, which could be due to its undesirable physicochemical and pharmacokinetic properties. In this study, we investigated the structure-activity and structure-property relationships around the 2'-hydroxyl group of sw-22 to improve the physicochemical properties, pharmacokinetic properties and anti-tumor activity.

Discovery of novel aromatase inhibitors using a homogeneous time-resolved fluorescence assay.

Aim: Aromatase is an important target for drugs to treat hormone-dependent diseases, including breast cancer. The aim of this study was to develop a homogeneous time-resolved fluorescence (HTRF) aromatase assay suitable for high-throughput screening (HTS).

Methods: A 384-well aromatase HTRF assay was established, and used to screen about 7000 compounds from a compound library.

Inclusion of quinestrol and 2,6-di-O-methyl-β-cyclodextrin: Preparation, characterization, and inclusion mode.

An inclusion complex between chemosterilant quinestrol and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) was prepared using the solution-ultrasonic method. A 1:1 stoichiometry was confirmed by elemental analysis. Analytical techniques such as UV-vis spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy were used to characterize the complex.

Identification of novel polo-like kinase 1 inhibitors by a hybrid virtual screening.

Polo-like kinase 1 is an important and attractive oncological target that plays a key role in mitosis and cytokinesis. A combined pharmacophore- and docking-based virtual screening was performed to identify novel polo-like kinase 1 inhibitors. A total of 34 hit compounds were selected and tested in vitro, and some compounds showed inhibition of polo-like kinase 1 and human tumor cell growth.

Combined pharmacophore modeling, docking, and 3D-QSAR studies of PLK1 inhibitors.

Polo-like kinase 1, an important enzyme with diverse biological actions in cell mitosis, is a promising target for developing novel anticancer drugs. A combined molecular docking, structure-based pharmacophore modeling and three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a set of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. The common substructure, molecular docking and pharmacophore-based alignment were used to develop different 3D-QSAR models.

Structure-based and shape-complemented pharmacophore modeling for the discovery of novel checkpoint kinase 1 inhibitors.

Checkpoint kinase 1 (Chk1), a member of the serine/threonine kinase family, is an attractive therapeutic target for anticancer combination therapy. A structure-based modeling approach complemented with shape components was pursued to develop a reliable pharmacophore model for ATP-competitive Chk1 inhibitors. Common chemical features of the pharmacophore model were derived by clustering multiple structure-based pharmacophore features from different Chk1-ligand complexes in comparable binding modes.