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Leukemia stem cells (LSCs) that survive conventional chemotherapy are thought to contribute to disease relapse, leading to poor long-term outcomes for patients with acute myeloid leukemia (AML). We previously identified a Src-family kinase (SFK) member, hematopoietic cell kinase (HCK), as a molecular target that is highly differentially expressed in human(More)
Cytochrome P450 (CYP) is deeply involved in the metabolism of chemicals including pharmaceuticals. Therefore, polymorphisms of this enzyme have been widely studied to avoid unfavorable side effects of drugs in chemotherapy. In this work, we performed computational analysis of the mechanism of the decrease in enzymatic activity for three typical(More)
Human CYP3A4 catalyzes the 10,11-epoxidation of carbamazepine (CBZ). However, the epoxide is less stable in terms of potential energy than hydroxides of the six-membered aromatic ring. To clarify the reason why CYP3A4 produces such an energetically unfavorable compound, the mechanism of epoxidation of CBZ by CYP3A4 was investigated by theoretical(More)
To ensure a continuing pipeline in pharmaceutical research, lead candidates must possess appropriate metabolic stability in the drug discovery process. In vitro ADMET (absorption, distribution, metabolism, elimination, and toxicity) screening provides us with useful information regarding the metabolic stability of compounds. However, before the synthesis(More)
A new screening method using fluorescent correlation spectroscopy was developed to select kinase inhibitors that competitively inhibit the binding of a fluorescently labeled substrate peptide. Using the method, among approximately 700 candidate compounds selected by virtual screening, we identified a novel Pim-1 kinase inhibitor targeting its peptide(More)
In drug discovery process, improvement of ADME/Tox properties of lead compounds including metabolic stability is critically important. Cytochrome P450 (CYP) is one of the major metabolizing enzymes and the prediction of sites of metabolism (SOM) on the given lead compounds is key information to modify the compounds to be more stable against metabolism.(More)
No explicit pi-pi interaction term has been incorporated in the conventional molecular dynamics (MD) simulation programs in spite of its significant role in the folding of biomolecules and the clustering of organic chemicals. In this article, we propose a technique to emphasize the effect of pi-pi interactions using a function of energy and implement it(More)
Protein functions are closely related to their three-dimensional structures. Various degrees of conformational changes in the main and side chains occur when binding with other molecules, such as small ligands or proteins. The ligand-induced structural polymorphism of proteins is also referred to as "induced-fit", and it plays an important role in the(More)
Marine aquaculture and stock enhancement are major causes of the introduction of alien species. A good example of such an introduction is the Japanese shortneck clam Ruditapes philippinarum, one of the most important fishery resources in the world. To meet the domestic shortage of R. philippinarum caused by depleted catches, clams were imported to Japan(More)
In this study, machine learning using support vector machine was combined with three-dimensional (3D) molecular shape overlay, to improve the screening efficiency. Since the 3D molecular shape overlay does not use fingerprints or descriptors to compare two compounds, unlike 2D similarity methods, the application of machine learning to a 3D shape-based(More)