Predictability of pathogenesis of allergic contact dermatitis based on specific chemical structure caused by metabolic activation.

• Project/Area Number: 17K15493
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Nihon Pharmaceutical University
• Principal Investigator: URAMARU NAOTO 日本薬科大学, 薬学部, 講師 (90424069)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 薬物アレルギー / 薬物代謝 / ドラッグデザイン / 構造活性相関 / 薬学

Outline of Final Research Achievements

Drug allergy is rare, but seriously and potentially life-threatening.In this study, we designed several Non-Steroidal Anti-Inflammatory Drug (NSAIDs) compounds with substituents that were expected to avoiding metabolic activation. Our research idea expect the validity of our strategy of blocking metabolic activation of NASIDs by means of structural modification compounds that can not be metabolically activated to bind to biomacromolecules and so do not show allergenicity.

Academic Significance and Societal Importance of the Research Achievements

アレルギー性接触皮膚炎（Allergic Contact Dermatitis）は医薬品、香粧品等で使用されている化学物質（環境化学物質を含む）により起因することが知られており、化学物質の使用前の薬物アレルギー発症予測は困難であり、薬物アレルギー反応を正確に予測する手段は見出されていない。本研究では、化学物質の生体内代謝反応と化学構造的要因から薬物アレルギー発症予測に寄与することを目的としている。

Research Products

• [Int'l Joint Research] 中国医薬大学(台湾)
• [Int'l Joint Research] 中国医薬大学(台湾)
• [Int'l Joint Research] 中国医薬大学(台湾)
• [Journal Article] Selective Synthesis and Photoluminescence Study of Pyrazolopyridopyridazine Diones and N-Aminopyrazolopyrrolopyridine Diones (2020)
  • Author(s): Tseng Ching-Chun、Chung Cheng-Yen、Tsai Shuo-En、Takayama Hiroyuki、Uramaru Naoto、Lin Chin-Yu、Wong Fung Fuh
  • Journal Title: Molecules Volume: 25 Issue: 10 Pages: 2409-2409
  • DOI: 10.3390/molecules25102409
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthesis and evaluation of in vitro bioactivity for polysubstituted N-arylpyrazole derivatives (2019)
  • Author(s): Uramaru Naoto、Chang En-Chiuan、Yen Wan-Ping、Yeh Mou-Yung、Juang Shin-Hun、Wong Fung Fuh
  • Journal Title: Arabian Journal of Chemistry Volume: 12 Issue: 8 Pages: 1908-1917
  • DOI: 10.1016/j.arabjc.2014.12.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Activation of PXR, CAR and PPARalpha by pyrethroid pesticides and effect of the metabolism by rat liver microsomes. (2019)
  • Author(s): 2.Fujino C, Watanabe Y, Sanoh S, Nakajima H, Uramaru N, Kojima H, Yoshinari K, Ohta S, Kitamura S.
  • Journal Title: Heliyon Volume: 5 Issue: 9 Pages: e02466-e02466
  • DOI: 10.1016/j.heliyon.2019.e02466
  • Peer Reviewed / Open Access
• [Journal Article] Comparative study of the effect of 17 parabens on PXR-, CAR- and PPARalpha-mediated transcriptional activation. (2019)
  • Author(s): 1.Fujino C, Watanabe Y, Sanoh S, Hattori S, Nakajima H, Uramaru N, Kojima H, Yoshinari K, Ohta S, Kitamura S.
  • Journal Title: Food and Chemical Toxicology Volume: 133 Pages: 110792-110792
  • DOI: 10.1016/j.fct.2019.110792
  • Peer Reviewed
• [Journal Article] Selective synthesis of functionalized pyrazoles from 5-amino-1H-pyrazole-4-carbaldehydes with sodium nitrite: 5-Amino-4-nitrosopyrazoles and pyrazole-4-carbaldehydes (2019)
  • Author(s): Hsiao Rong-Hong、Tseng Ching-Chun、Xie Jia-Jun、Tsai Shuo-En、Uramaru Naoto、Lin Ching-Ya、Chern Ching-Yuh、Wong Fung Fuh
  • Journal Title: Tetrahedron Volume: 75 Issue: 33 Pages: 4561-4569
  • DOI: 10.1016/j.tet.2019.06.048
  • Peer Reviewed
• [Journal Article] Profiling of bisphenol A and eight its analogues on transcriptional activity via human nuclear receptors (2019)
  • Author(s): Hiroyuki Kojima, Shinji Takeuchi, Seigo Sanoh, Katsuhiro Okuda, Shigeyuki Kitamura, Naoto Uramaru, Kazumi Sugihara, Kouichi Yoshinari
  • Journal Title: Toxicology, 413(2),48-55, Volume: 413 Pages: 48-55
  • DOI: 10.1016/j.tox.2018.12.001
  • Peer Reviewed / Open Access
• [Journal Article] Efficient acid catalytic synthesis of pyrazolopyrimidines from 1H-pyrazol-5-yl-N,N-dimethylformamidines with cyanamide. (2018)
  • Author(s): Tsai S. E., Yen W. P., Tseng C. C., Xie J. J., Liou M. Y., Li Y. T., Uramaru N., Wong F. F.
  • Journal Title: Tetrahedron Volume: 74 Issue: 22 Pages: 2787-2791
  • DOI: 10.1016/j.tet.2018.04.048
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of hepatic thyroid hormone-responsive genes in neonatal rats: Potential targets for thyroid hormone-disrupting chemicals. (2018)
  • Author(s): Fujimoto N., Kitamura S., Uramaru N., Miyagawa S., Iguchi T.
  • Journal Title: Toxicology Letters Volume: 286 Pages: 48-53
  • DOI: 10.1016/j.toxlet.2018.01.005
  • Peer Reviewed / Open Access
• [Journal Article] Construction of the Database of Rat Repeated-dose Toxicity Tests of Pesticides for the Toxicological Characterization of Hepatocyte Hypertrophy (2017)
  • Author(s): 増田茜、増田雅美、中島宏之、小島弘幸、北村繁幸、浦丸直人、保坂卓臣、佐々木崇光、吉成浩一―
  • Journal Title: YAKUGAKU ZASSHI Volume: 137 Issue: 5 Pages: 611-622
  • DOI: 10.1248/yakushi.16-00259
  • NAID: 130005631433
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2017-05-01
  • Peer Reviewed / Open Access
• [Journal Article] Protective effects of tormentic Acid, a major component of suspension cultures of eriobotrya japonica cells, on acetaminophen-induced hepatotoxicity in mice. (2017)
  • Author(s): Jiang W. P., Huang S. S., Matsuda Y., Saito H., Uramaru N., Ho H. Y., Wu J. B., Huang G. J.
  • Journal Title: Molecules Volume: 22(5) Issue: 5 Pages: 830-830
  • DOI: 10.3390/molecules22050830
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] One-flask synthesis of pyrazolo[3,4-d]pyrimidines from 5-aminopyrazoles and mechanistic study. (2017)
  • Author(s): Yen W. P., Tsai S. E., Uramaru N., Takayama H., Wong F.F.
  • Journal Title: Molecules, 22(5), 820/1-820/12 (2017). Volume: 22(5) Issue: 5 Pages: 820-820
  • DOI: 10.3390/molecules22050820
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Altered expression of Olr59, Ethe1, and Slc10a2 genes in the liver of F344 rats by neonatal thyroid hormone disruption. (2017)
  • Author(s): Matsubara K et al.
  • Journal Title: J Appl Toxicol Volume: - Issue: 9 Pages: 1030-1035
  • DOI: 10.1002/jat.3452
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis and antiproliferative activity of 3α-hydroxyl-3β-methoxymethyl-5α-pregnan-20-one with a C-21 hydrophilic substituent. (2017)
  • Author(s): Tsai S. E., Lee J. C., Uramaru, N., Takayama H., Huang G. J., Wong F. F.
  • Journal Title: Heteroatom Chemistry Volume: 28(3) Issue: 3 Pages: e21372-e21372
  • DOI: 10.1002/hc.21372
  • Peer Reviewed / Int'l Joint Research
• [Presentation] ラズベリーケトンの還元代謝物であるロドデノールによる脂肪蓄積抑制 (2019)
  • Author(s): 浦丸 直人，鈴木 智貴，木根淵 有香，川村 諒，渡部 容子，長部 誠，樋口 敏幸
  • Organizer: フォーラム2019衛生薬学・環境トキシコロジー
• [Presentation] Common behavioral characteristics in the mice maternally exposed to different types of dioxins. (2019)
  • Author(s): Maekawa F., Kimura E., Uramaru N., Suzuki G.
  • Organizer: 9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS 2019)
  • Int'l Joint Research
• [Presentation] Behavioral impairments of infant and adult mice exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation. (2019)
  • Author(s): Kimura E., Uramaru N., Suzuki G., Mekawa F.
  • Organizer: 58th Annual Meeting and ToxExpo (Society of Toxicology)
  • Int'l Joint Research
• [Presentation] ラズベリーケトンの還元的代謝および3T3-L1 細胞の脂肪化抑制 (2019)
  • Author(s): 浦丸 直人，坂本 佳澄，鈴木 智貴，木根淵 有香，川村 涼，渡部 容子，北村 繁幸，樋口 敏幸
  • Organizer: 日本薬学会第139年会
• [Presentation] PM2.5由来抽出物質によるTissue factor の発現誘導 (2019)
  • Author(s): 小畑 りさ，種田 千夏，村橋 毅，浦丸 直人，長部 誠，渡部 容子，樋口 敏幸
  • Organizer: 日本薬学会第139年会
• [Presentation] 環境中に存在する臭素系ダイオキシンの発達期曝露により誘導される行動異常 (2018)
  • Author(s): 木村栄輝，鈴木剛，浦丸直人，前川文彦
  • Organizer: 第189回日仏生物学会例会
• [Presentation] 高脂肪食負荷および通常食ラットにおけるシトクロムP450 活性/ 発現の比較検討 (2018)
  • Author(s): 浦丸 直人，島田 沙保，厚川 雄大，渡部 容子，樋口 敏幸
  • Organizer: フォーラム2018 衛生薬学・環境トキシコロジー