Ken Yamada
Novartis
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Publication
Featured researches published by Ken Yamada.
International Journal of Toxicology | 2017
Alan P. Brown; Chandrassegar Saravanan; Patrick J. Devine; Maria Magnifico; Jiaping Gao; Valerie Beaulieu; Fupeng Ma; Kayo Yasoshima; David Barnes-Seeman; Ken Yamada
This research provides a cautionary example when evaluating changes in behavioral end points with respect to postulated pharmacologic activity. Various small molecule substrate mimetic protein tyrosine phosphatase 1B (PTP1B) inhibitors were investigated as pharmacologic agents for decreasing food consumption using intranasal (IN) dosing as a means for direct nose-to-brain delivery along the olfactory/trigeminal nerve pathways. Although food consumption was decreased in diet-induced obese (DIO) mice, nasal discharge was observed. Studies were conducted to investigate local effects on the nasal airway and to develop structure–activity relationships. Intranasal administration of PTP1B inhibitors at ≥0.03 mg/d to DIO mice produced dose-dependent injury to various cell types of the nasal epithelia. Protein tyrosine phosphatase 1B inhibitors with calculated log octanol >3.0 were the most toxic. Whereas a pharmacologically inactive analog of a PTP1B inhibitor produced nasal injury, along with decreased food consumption, the marketed IN drug ketorolac produced no lesions at the same dose of 0.3 mg/d and only minor changes at 3 mg/d. Rat skin fibroblast cells were exposed in vitro to PTP1B inhibitors, ketorolac, paraquat, and the detergent sodium dodecylbenzene sulfonate (NDS) followed by measures of cytotoxicity. The most potent PTP1B inhibitors were similar to NDS, whereas ketorolac was the least toxic compound. Cytotoxic potency in vitro was similar to in vivo. In conclusion, PTP1B inhibitors injured nasal epithelium through a mechanism independent of PTP1B inhibition and likely due to nonspecific cytotoxicity such as disruption of the cell membrane. Decreased food consumption in DIO mice was due to toxicity rather than a pharmacologic mode of action.
Archive | 2007
Hidetomo Imase; Yuki Iwaki; Toshio Kawanami; Takahiro Miyake; Muneto Mogi; Osamu Ohmori; Hongbo Qin; Ichiro Umemura; Ken Yamada; Kayo Yasoshima
Archive | 2008
Muneto Mogi; Toshio Kawanami; Ken Yamada; Kayo Yasoshima; Hidetomo Imase; Takahiro Miyake; Osamu Ohmori
Archive | 2006
Junichi Sakaki; Masashi Kishida; Naoko Matsuura; Ichiro Umemura; Eiji Kawahara; Ken Yamada; Kazuhide Konishi; Yuki Iwaki; Hidetomo Imase; Takahiro Miyake
Archive | 2008
Muneto Mogi; Ken Yamada; Kayo Yasoshima; Toshio Kawanami; Ichiro Umemura; Yuki Iwaki; Hongbo Qin; Hidetomo Imase
Archive | 2015
David Barnes; Ken Yamada; Chikwendu Ibebunjo; Alokesh Duttaroy; Louise Kirman; Alexandra Marshall Bruce; Aimee Richardson Usera; Frédéric Zecri; Jun Yuan; Changgang Lou; Aaron Kanter; Avirup Bose
Archive | 2012
Yoshie Arai; Margaret Elizabeth Brousseau; Jessie Gu; Tomoko Hayashi; Hironobu Mitani; Muneto Mogi; Kazuhiko Nonomura; Ken Yamada
Archive | 2017
Frédéric Zecri; Aaron Kanter; Changgang Lou; Aimee Richardson Usera; Alexandra Marshall Bruce; Jun Yuan; David Barnes; Ken Yamada; Chikwendu Ibebunjo; Alokesh Durraroy; Louise Kirman; Avirup Bose
Archive | 2016
Avirup Bose; Aaron Kanter; Changgang Lou; Jun Yuan; Frdric Zecri; Aimee Richardson Usera; Alexandra Marshall Bruce; Louise Kirman; Alokesh Duttaroy; Chikwendu Ibebunjo; Ken Yamada; David Barnes
Archive | 2012
Muneto Mogi; Ken Yamada; Kayo Yasoshima; Toshio Kawanami; Ichiro Umemura; Yuki Iwaki; Hongbo Qin; Hidetomo Imase