test compounds 1–14  (WuXi AppTec)

Journal: Journal of Medicinal Chemistry

Article Title: Identification of Novel Human 15-Lipoxygenase-2 (h15-LOX-2) Inhibitors Using a Virtual Screening Approach

doi: 10.1021/acs.jmedchem.4c01884

Figure Lengend Snippet: Structures of some h15-LOX-2 inhibitors reported in the literature. , −

Article Snippet: Compounds tested as inhibitors ( 1 – 14 ) were purchased from MolPort ( Molport SIA , Riga, Latvia) and are >88% pure.

Techniques:

Journal: Journal of Medicinal Chemistry

Article Title: Identification of Novel Human 15-Lipoxygenase-2 (h15-LOX-2) Inhibitors Using a Virtual Screening Approach

doi: 10.1021/acs.jmedchem.4c01884

Figure Lengend Snippet: Schematic representation of the virtual screening (VS) protocol used in this study to select novel potential h15-LOX-2 inhibitors from the ZINC-Curated database. (A) Representation of the sequence of selection filters applied to the ZINC-Curated database in each VS step. (B) Schematic representation of the steps to generate the shape-based model that was used as the first filter in the VS protocol: 1. Alignment of low energy conformation structures of two known h15-LOX-2 inhibitors ( LIT-04 and LIT-05 ), using LigandScout’s alignment algorithm, and 2. Shape-based model generation using ROCS. The molecular shape surface is represented in gray. The figure was prepared by using LigandScout and ROCS.

Article Snippet: Compounds tested as inhibitors ( 1 – 14 ) were purchased from MolPort ( Molport SIA , Riga, Latvia) and are >88% pure.

Techniques: Sequencing, Selection

Journal: Journal of Medicinal Chemistry

Article Title: Identification of Novel Human 15-Lipoxygenase-2 (h15-LOX-2) Inhibitors Using a Virtual Screening Approach

doi: 10.1021/acs.jmedchem.4c01884

Figure Lengend Snippet: Score frequency distributions of the best-ranked docking poses for the compounds selected from the ZINC-Curated database after applying the docking filter. (A) ChemPLP score values distribution. (B) Goldscore score values distribution. The figure was prepared using GraphPad Prism. The ChemPLP and Goldscore score values of two h15-LOX-2 known inhibitors ( LIT-01 and LIT-05 ) are represented for comparison.

Article Snippet: Compounds tested as inhibitors ( 1 – 14 ) were purchased from MolPort ( Molport SIA , Riga, Latvia) and are >88% pure.

Techniques: Comparison

Journal: Journal of Medicinal Chemistry

Article Title: Identification of Novel Human 15-Lipoxygenase-2 (h15-LOX-2) Inhibitors Using a Virtual Screening Approach

doi: 10.1021/acs.jmedchem.4c01884

Figure Lengend Snippet: Schematic representations of the predicted binding modes (best-scored docking solutions) of the h15-LOX-2 inhibitors selected by the VS protocol proposed in this study: (A) Compound 07 ; (B) compound 10 ; (C) compound 11 ; (D) compound 12 ; (E) compound 13 ; and (F) compound 14 . The crystal structure of h15-LOX-2 (PDB code: 4NRE ; resolution: 2.63 Å) was used for all docking calculations. Left panels : Schematic representations of the best-scored docking solutions for each inhibitor inside the h15-LOX-2 active site’s cavity. For clarity, only the active site residues that interact with each inhibitor are highlighted (shown as sticks). Catalytic iron is shown as a brown sphere. A water molecule that coordinates iron and makes a hydrogen-bond interaction with compounds 10 and 12 is shown as a red sphere in panels (B, D). Central panels : Schematic representations of the best-scored docking solutions for each compound, with h15-LOX-2 active site’s cavity represented as a surface to highlight its U-shaped format. The inhibitors occupy the more solvent-exposed arm of the cavity, which corresponds to the cavity’s right arm in the protein’s orientation captured to prepare this figure. Right panels : 2D Schematic representations of the protein–ligand interactions identified using the LigandScout program. Yellow: hydrophobic interactions; blue circle/arrow: pi-cation interactions; blue cones: ionic interactions; red arrows: hydrogen-bond acceptor interactions; pink arrow: halogen bond interaction. The figure was prepared using PyMOL.

Article Snippet: Compounds tested as inhibitors ( 1 – 14 ) were purchased from MolPort ( Molport SIA , Riga, Latvia) and are >88% pure.

Techniques: Binding Assay, Solvent

Journal: Journal of Medicinal Chemistry

Article Title: Identification of Novel Human 15-Lipoxygenase-2 (h15-LOX-2) Inhibitors Using a Virtual Screening Approach

doi: 10.1021/acs.jmedchem.4c01884

Figure Lengend Snippet: Structures and Inhibitory Activities (Percentages of Inhibition at 10 or 1 μM) of the Compounds Selected as Potential h15-LOX-2 Inhibitors Using the VS Protocol Proposed in this Study

Article Snippet: Compounds tested as inhibitors ( 1 – 14 ) were purchased from MolPort ( Molport SIA , Riga, Latvia) and are >88% pure.

Techniques: Inhibition