2013 Fiscal Year Final Research Report
Identification of molecular mechanism for actions of NSAID and its application for drug development
Project/Area Number |
24790113
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Drug development chemistry
|
Research Institution | Shujitsu University (2013) Keio University (2012) |
Principal Investigator |
|
Project Period (FY) |
2012-04-01 – 2014-03-31
|
Keywords | 医薬品探索 |
Research Abstract |
In this study, we have examined the gene changing expression frequency after target NSAIDs treatment. As a result, we identified a series of NSAIDs that changed heat shock protein-related genetic expression. As a result of being interesting, we found that carboxylic acid-based NSAIDs greatly changes expression of HSP25 and HSP27. We identified a cytotoxic weak NSAID with superior anti-inflammatory action. However, an expected effect was not provided at the animal level. Therefore we synthesized the derivative of the target NSAID that we identified and discovered new compounds with a few gastric ulcer side effects.
|
-
[Journal Article] Superiority of pulmonary administration of mepenzolate bromide over other routes as treatment for chronic obstructive pulmonary disease2014
Author(s)
Tanaka, K., Kurotsu, S., Asano, T., Yamakawa, N., Kobayashi, D., Yamashita, Y., Yamazaki, H., Ishihara, T., Watanabe, H., Maruyama, T., Suzuki, H. and Mizushima, T
-
Journal Title
Sci Rep
Volume: 4
Pages: 4510
-
[Journal Article] Structure-activity relationship of celecoxib and rofecoxib for the membrane permeabilizing activity2014
Author(s)
Yamakawa, N., Suzuki, K., Yamashita, Y., Katsu, T., Hanaya, K., Shoji, M., Sugai, T. and Mizushima, T
-
Journal Title
Bioorg Med Chem
Volume: 22
Pages: 2529-2534
-
[Journal Article] Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities2014
Author(s)
Yamashita, Y., Tanaka, K., Asano, T., Yamakawa, N., Kobayashi, D., Ishihara, T., Hanaya, K., Shoji, M., Sugai, T., Wada, M., Mashimo, T., Fukunishi, Y. and Mizushima, T
-
Journal Title
Bioorg Med Chem
Volume: 22
Pages: 3488-3497
-
[Journal Article] Suppression of Alzheimer's Disease-Related Phenotypes by Geranylgeranylacetone in Mice2013
Author(s)
Hoshino, T., Suzuki, K., Matsushima, T., Yamakawa, N., Suzuki, T. and Mizushima, T
-
Journal Title
PLoS One
Volume: 8
Pages: 76306
-
[Journal Article] Prostaglandin E1 -containing nanoparticles improve walking activity in an experimental rat model of intermittent claudication2013
Author(s)
Ishihara, T., Yamashita, Y., Takasaki, N., Yamamoto, S., Hayashi, E., Tahara, K., Takenaga, M., Yamakawa, N., Kasahara, T. and Mizushima, T
-
Journal Title
J Pharm Pharmacol
Volume: 65
Pages: 1187-1194
-
[Journal Article] Suppression of UV-induced wrinkle formation by induction of HSP70 expression in mice2013
Author(s)
Matsuda, M., Hoshino, T., Yamakawa, N., Tahara, K., Adachi, H., Sobue, G., Maji, D., Ihn, H. and Mizushima, T
-
Journal Title
J Invest Dermatol
Volume: 132
Pages: 919-928
-
[Journal Article] Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease2013
Author(s)
Tanaka, K., Ishihara, T., Sugizaki, T., Kobayashi, D., Yamashita, Y., Tahara, K., Yamakawa, N., Iijima, K., Mogushi, K., Tanaka, H., Sato, K., Suzuki, H. and Mizushima, T
-
Journal Title
Nat Commun
Volume: 4
Pages: 2686
-
[Journal Article] Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity, fluoro-loxoprofen2013
Author(s)
Yamakawa, N., Suemasu, S., Watanabe, H., Tahara, K., Tanaka, K., Okamoto, Y., Ohtsuka, M., Maruyama, T. and Mizushima, T
-
Journal Title
Drug Metab Pharmacokinet
Volume: 28
Pages: 118-124
-
[Journal Article] Identification of a unique nsaid, fluoro-loxoprofen with gastroprotective activity2012
Author(s)
Suemasu, S., Yamakawa, N., Ishihara, T., Asano, T., Tahara, K., Tanaka, K., Matsui, H., Okamoto, Y., Otsuka, M., Takeuchi, K., Suzuki, H. and Mizushima, T
-
Journal Title
Biochem Pharmacol
Volume: 84
Pages: 1470-1481
-
[Journal Article] Expression of 150-kDa oxygen-regulated protein (ORP150) stimulates bleomycin-induced pulmonary fibrosis and dysfunction in mice2012
Author(s)
Tanaka, K., Shirai, A., Ito, Y., Namba, T., Tahara, K., Yamakawa, N. and Mizushima, T
-
Journal Title
Biochem Biophys Res Commun
Volume: 425
Pages: 818-824
-
[Journal Article] Synthesis and Biological Evaluation of Derivatives of 2-{2-Fluoro-4-[(2-oxocyclopentyl)methyl ]phenyl}propanoic Acid : Nonsteroidal Anti-Inflammatory Drugs with Low Gastric Ulcerogenic Activity2012
Author(s)
Yamakawa, N., Suemasu, S., Okamoto, Y., Tanaka, K., Ishihara, T., Asano, T., Miyata, K., Otsuka, M. and Mizushima, T
-
Journal Title
Journal of Medicinal Chemistry
Volume: 55
Pages: 5143-5150