Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments.

Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work.

Discovery of novel indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors by virtual screening.

In this study, a combination of virtual screening methods were utilized to identify novel potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. A series of IDO1 potential inhibitors were identified by a combination of following steps: Lipinski's Rule of Five, Veber rules filter, molecular docking, HipHop pharmacophores, 3D-Quantitative structure activity relationship (3D-QSAR) studies and Pan-assay Interference Compounds (PAINS) filter. Three known categories of IDO1 inhibitors were used to constructed pharmacophores and 3D-QSAR models.

Pharmacophore modeling, molecular docking and molecular dynamics simulations toward identifying lead compounds for Chk1.

Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase, plays an important role in G2/M checkpoint, which is a key regulator in response to DNA damage. In this study, the structure-based drug design approach and molecular dynamics (MD) simulations were used to explore potent Chk1 inhibitors. A series of the best fitting candidates were picked out from the Specs database.

Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-purine xanthine oxidase inhibitors.

Gout is a common inflammatory arthritis caused by the deposition of urate crystals within joints. It is increasingly in prevalence during the past few decades as shown by the epidemiological survey results. Xanthine oxidase (XO) is a key enzyme to transfer hypoxanthine and xanthine to uric acid, whose overproduction leads to gout.

Discovery of FIXa inhibitors by combination of pharmacophore modeling, molecular docking, and 3D-QSAR modeling.

Human Coagulation Factor IXa (FIXa), specifically inhibited at the initiation stage of the blood coagulation cascade, is an excellent target for developing selective and safe anticoagulants. To explore this inhibitory mechanism, 86 FIXa inhibitors were selected to generate pharmacophore models and subsequently SAR models. Both best pharmacophore model and ROC curve were built through the Receptor-Ligand Pharmacophore Generation module.

In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking.

Coagulation Factor Xa (FXa) is the crucial enzyme at the convergent point of the intrinsic and extrinsic coagulation pathways. The inhibition of FXa is an effective approach against thrombotic diseases. In the present study, a specific strategy is reported to discover 10 novel FXa inhibitors based on ligand-based (pharmacophore) virtual screening and molecular docking analysis from a dataset of specs(containing 220000 molecules).