Tohoku University · Biochemistry, Genetics and Molecular Biology
Professor Minoru Ishikawa's research lab focuses on innovative strategies in drug discovery and medicinal chemistry, particularly enhancing the aqueous solubility and bioavailability of small molecule drugs through molecular design—such as disrupting planarity and symmetry or employing photoresponsive switches like azobenzene. The lab also investigates the modulation of cytochrome P450 enzymes by cyclodextrin derivatives and develops novel therapeutic approaches, including PROTACs and SNIPERs, for targeting undruggable proteins. Their work bridges chemical innovation with translational potential in treating cancer and hormone-dependent diseases.
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ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTImprovement in Aqueous Solubility in Small Molecule Drug Discovery Programs by Disruption of Molecular Planarity and SymmetryMinoru Ishikawa* and Yuichi HashimotoView Author Information Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan*Phone: +81.3.5841.7849. Fax: +81.3.5841.8495. E-mail: [email protected]Cite this: J. Med. Chem. 2011, 54, 6, 1539–1554Publication Date (Web):February
The effects of modified cyclodextrins (CDs) hydroxypropyl-beta-CD and methyl-beta-CD were studied in vitro on cDNA-expressed human cytochrome P-450 (CYP) activities (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). The modified CDs inhibited the activities of CYP2C19 and CYP3A4 while enhancing CYP2C9 activity by 140 to 176% relative to the control values at lower concentrations. In addition, methyl-beta-CD inhibited CYP1A2 and CYP2D6 at higher concentrations.
The reduction behavior of dephosphorization slag on the iron bath in the reduction furnace of the slag regeneration process was researched by test converter experiments. Dephosphorization slag and coke as the reduction agent and the heat source were added to the hot metal in the converter and oxygen was blown through the top lance. During the blowing, the reduction of (P2O5), (FeO) and (MnO) in the slag proceeded simultaneously. The amount of phosphorus and manganese oxide in the slag decreased
We previously showed that disruption of intermolecular interactions, e.g., by lowering the molecular planarity and/or introducing bent structures, improves the aqueous solubility of compounds, and based upon that work, we hypothesized that azobenzene trans-to-cis photoswitching could also be utilized to enhance the aqueous solubility of compounds. Here, we demonstrate that UV/visible light irradiation can reversibly switch the aqueous solubilization of an anti-cancer candidate drug, a low-molecu
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