A neurokinin 2 (NK2) antagonist pharmacophore model has been developed on the basis of five non-peptide antagonists from several structurally diverse classes. To evaluate the pharmacophore model, another 20 antagonists were fitted to the model. By use of exhaustive conformational analysis (MMFFs force field and the GB/SA hydration model) and least-squares molecular superimposition studies, 23 o...

Adenylate kinase 3 (AK3) is an enzyme located in the mitochondrial matrix involved purine homeostasis. This protein has been considered a potential therapeutic target chronic lymphocytic leukemia (CLL), because silencing of AK3 gene inhibited cell growth CLL vitro models. study aimed to design inhibitors by applying molecular modeling techniques. Through mapping binding sites, essential interac...

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The aim of this study was to use a combined structure and pharmacophore modeling approach to extract information regarding dopamine D₁ receptor agonism and D₁/D₂ agonist selectivity. A 3D structure model of the D₁ receptor in its agonist-bound state was constructed with a full D₁ agonist present in the binding site. Two different binding modes were identified using (+)-doxanthrine or SKF89626 i...

Neuronal nitric oxide synthase (nNOS) plays an important role in neurotransmission and smooth muscle relaxation. Selective inhibition of nNOS over its other isozymes is highly desirable for the treatment of neurodegenerative diseases to avoid undesirable effects. In this study, we present a workflow for the identification and prioritization of compounds as potentially selective human nNOS inhib...

Limited progress has been made in the quest to identify both selective and non-toxic T-type calcium channel blocking compounds. The present research work was directed toward slaking the same by identifying the selective three dimensional (3D) pharmacophore map for T-type calcium channel blockers (CCBs). Using HipHop module in the CATALYST 4.10 software, both selective and non-selective HipHop p...

During the past few years, pharmacophore modeling has become one of the key components in computer-aided drug design and in modern drug discovery. DrugOn is a fully interactive pipeline designed to exploit the advantages of modern programming and overcome the command line barrier with two friendly environments for the user (either novice or experienced in the field of Computer Aided Drug Design...

Glucagon and the glucagon receptor are most important molecules control over blood glucose concentrations. These two molecules are very important to studies of type 2 diabetic patients. In literature, several classes of small molecule antagonists of the human glucagon receptor have been reported. Glucagon receptor antagonist could decrease hepatic glucose output and improve glucose control in d...

Novel 5H-thiazolo[3,2-a]pyrimidin-5-one derivatives linked through an ethylene bridge to various phenylpiperazine groups were prepared for evaluation as 5-HT2A receptor antagonists. The target compounds 11a–p were prepared through the initial synthesis of the 2-chloroethyl intermediates 10a–d which were then reacted with the appropriate phenylpiperazines. All compounds were tested for their ant...

We present the discovery of innovative low molecular weight inhibitors against human immunodeficiency virus 1 (HIV-1) protease. Structure-based virtual screening focused on potential allosteric surface cavities revealed these compounds [1]. To identify and prioritize such cavities we performed a molecular dynamics simulation were we concentrated on flexible and transient potential binding sites...