Member

Research Theme

1. Medicinal Chemistry of Retinoid
   Retinoids are specific modulators of cell proliferation, differentiation, and morphogenesis in vertebrates. The pleiotropic activities of retinoids are mediated by binding to and activating two classes of nuclear receptors, RARs and RXRs. We are developing novel synthetic RAR and RXR agonists/antagonists. Among them, an RAR agonist, Am80 (tamibarotene) was approved as a drug for relapsed acute promyelocytic leukemia (APL) in Japan (2005).
2. Medicinal Chemistry of Nuclear Receptors
   Nuclear receptors are ligand-inducible transcription factors that regulate the expression of their target genes. Nuclear receptors have become one of the most significant molecular targets for drug discovery in the fields of cancer, metabolic syndrome, autoimmune diseases, and so on. We are developing novel synthetic ligands for various nuclear receptors, including nuclear orphan receptors whose specific ligands are unknown.
3. Development of Novel Functional Fluorescent Molecules for Elucidation of Intracellular Signal Transduction Pathways
   Functional fluorescent molecules are useful in many fields of scientific research, including analytical chemistry or cell biology. We are developing novel fluoresecent molecules, whose fluorescence properties can be changed by binding to or reacting with ions, small molecules, or enzymes, enable us to estimate the concentration or activity of the targets.
4. Aromatic Architecture Based on the Steric Properties of N-Methylated Amides
   The amide bond often plays a key role in functions such as molecular recognition maps or biological activities. We found that most secondary amides, such as acetanilide and benzanilide, exist in the trans structure, while the corresponding N-methylated compounds exist in cis form in the crystals and predominantly in cis form in various solvents. We are developing armatic amides and related molecules with unique structures or conformational behaviors, and applying themin thefield of medicinal chemistry and materials science.

Publications

1. Komatsu, T.; Hirano, T.; Songkram, C.; Kawachi, E.; Kagechika, H. Novel Thyroid Hormone Receptor Antagonists With An N-Alkylated Diphenylamine Skeleton. Bioorg. Med. Chem. 2007, 15, 3115-3126.
2. Hirano, T.; Hiromoto, K.; Kagechika, H. Development of a Library of 6-Arylcoumarins as Candidate Fluorescent Sensors. Organic Lett. 2007, 9, 1315-1318.
3. Saito, A.; Sugawara, A.; Uruno, A.; Kudo, M.; Kagechika, H.; Sato, Y.; Owada, Y.; Kondo, H.; Sato, M.; Kurabayashi, M.; Imaizumi, M.; Tsuchiya, S.; Ito, S. All-trans Retinoic Acid Induces In Vitro Angiogenesis via Retinoic Acid Receptor: Possible Involvement of Paracrine Effects of Endogenous Vascular Endothelial Growth Factor Signaling. Endocrinol. 2007, 148, 1412-1423.
4. Haraguchi, G.; Suzuki, J.; Kosuge, H.; Ogawa, M.; Koga, N.; Muto, S.; Itai, A.; Kagechika, H.; Shudo, K.; Isobe, M. A New RXR Agonist, HX630, suppresses intimal hyperplasia in a mouse blood flow cessation model. J. Mol. Cell. Cardiol. 2006, 41, 885-892.
5. Yamasaki, R.; Tanatani, A.; Azumaya, I.; Masu, H.; Yamaguchi, K.; Kagechika, H. Solvent-Dependent Conformational Switching of N-Phenylhydroxamic Acid and Its Application in Crystal Engineering. Crystal Growth Des. 2006, 6, 2007-2010.
6. Calleja, C.; Messaddeq, N.; Chapellier, B.; Yang, H.; Krezel, W.; Li, M.; Metzger, D.; Mascrez, B.; Ohta, K.; Kagechika, H.; Endo, Y.; Mark, M.; Ghyselinck, N. B.; Chambon, P. Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes. Genes Develop. 2006, 20, 1525-1538.
7. Takeda, N.; Manabe, I.; Shindo, T.; Iwata, H.; Iimuro, S.; Kagechika, H.; Shudo, K.; Nagai, R. The synthetic retinoid Am80 reduces scavenger receptor expression and atherosclrosis in mice by inhibiting IL-6. Arterioscl. Thromb. Vas. 2006, 26, 1177-1183.