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16 results on '"Aida, Jumpei"'

2. Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel 1-(1H-benzimidazol-6-yl)pyridin-2(1H)-one derivatives and design to avoid CYP3A4 time-dependent inhibition

Author

Igawa, Hideyuki, Takahashi, Masashi, Shirasaki, Mikio, Kakegawa, Keiko, Kina, Asato, Ikoma, Minoru, Aida, Jumpei, Yasuma, Tsuneo, Okuda, Shoki, Kawata, Yayoi, Noguchi, Toshihiro, Yamamoto, Syunsuke, Fujioka, Yasushi, Kundu, Mrinalkanti, Khamrai, Uttam, Nakayama, Masaharu, Nagisa, Yasutaka, Kasai, Shizuo, and Maekawa, Tsuyoshi

Published
2016
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3. Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression

Author

Lama, Lodoe, Adura, Carolina, Xie, Wei, Tomita, Daisuke, Kamei, Taku, Kuryavyi, Vitaly, Gogakos, Tasos, Steinberg, Joshua I., Miller, Michael, Ramos-Espiritu, Lavoisier, Asano, Yasutomi, Hashizume, Shogo, Aida, Jumpei, Imaeda, Toshihiro, Okamoto, Rei, Jennings, Andy J., Michino, Mayako, Kuroita, Takanobu, Stamford, Andrew, Gao, Pu, Meinke, Peter, Glickman, J. Fraser, Patel, Dinshaw J., and Tuschl, Thomas

Published
2019
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5. Design, Synthesis, and Evaluation of [18F]T-914 as a Novel Positron-Emission Tomography Tracer for Lysine-Specific Demethylase 1

Author

Matsuda, Satoru, primary, Hattori, Yasushi, additional, Matsumiya, Kouta, additional, McQuade, Paul, additional, Yamashita, Tohru, additional, Aida, Jumpei, additional, Sandiego, Christine M., additional, Gouasmat, Alexandra, additional, Carroll, Vincent M., additional, Barret, Olivier, additional, Tamagnan, Gilles, additional, Koike, Tatsuki, additional, and Kimura, Haruhide, additional

Published
2021
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6. Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl Moiety

Author

Ikeda, Shuhei, primary, Sugiyama, Hideyuki, additional, Tokuhara, Hidekazu, additional, Murakami, Masataka, additional, Nakamura, Minoru, additional, Oguro, Yuya, additional, Aida, Jumpei, additional, Morishita, Nao, additional, Sogabe, Satoshi, additional, Dougan, Douglas R., additional, Gay, Sean C., additional, Qin, Ling, additional, Arimura, Naoto, additional, Takahashi, Yasuko, additional, Sasaki, Masako, additional, Kamada, Yusuke, additional, Aoyama, Kazunobu, additional, Kimoto, Kouya, additional, and Kamata, Makoto, additional

Published
2021
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7. Design and Identification of a GPR40 Full Agonist (SCO-267) Possessing a 2-Carbamoylphenyl Piperidine Moiety

Author

Furukawa, Hideki, primary, Miyamoto, Yasufumi, additional, Hirata, Yasuhiro, additional, Watanabe, Koji, additional, Hitomi, Yuko, additional, Yoshitomi, Yayoi, additional, Aida, Jumpei, additional, Noguchi, Naoyoshi, additional, Takakura, Nobuyuki, additional, Takami, Kazuaki, additional, Miwatashi, Seiji, additional, Hirozane, Yoshihiko, additional, Hamada, Teruki, additional, Ito, Ryo, additional, Ookawara, Mitsugi, additional, Moritoh, Yusuke, additional, Watanabe, Masanori, additional, and Maekawa, Tsuyoshi, additional

Published
2020
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8. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice

Author

Jessica Vincent, Aida Jumpei, Kazuyoshi Aso, L. Lama, Katherine Rothamel, Thomas Tuschl, J. Fraser Glickman, Carolina Adura, Antonio Luz, Tasos Gogakos, Seth A. Reasoner, Asano Yasutomi, Joshua Steinberg, Toshihiro Imaeda, Rei Okamoto, Pu Gao, Manuel Ascano, and Dinshaw J. Patel

Subjects
0301 basic medicine, Science, General Physics and Astronomy, Autoimmunity, Nervous System Malformations, Mass Spectrometry, Article, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, Small Molecule Libraries, Mice, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, Autoimmune Diseases of the Nervous System, 0302 clinical medicine, Downregulation and upregulation, Interferon, medicine, Animals, Enzyme Inhibitors, lcsh:Science, Gene, Benzofurans, Inflammation, chemistry.chemical_classification, Multidisciplinary, Innate immune system, ATP synthase, biology, Macrophages, DNA, General Chemistry, Nucleotidyltransferases, Publisher Correction, Small molecule, Immunity, Innate, High-Throughput Screening Assays, 3. Good health, 030104 developmental biology, Enzyme, chemistry, Biochemistry, biology.protein, lcsh:Q, 030217 neurology & neurosurgery, medicine.drug
Abstract

Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic GMP-AMP synthase synthesizes a cyclic dinucleotide that initiates an inflammatory cellular response. Mouse studies that recapitulate causative mutations in the autoimmune disease Aicardi-Goutières syndrome demonstrate that ablating the cyclic GMP-AMP synthase gene abolishes the deleterious phenotype. Here, we report the discovery of a class of cyclic GMP-AMP synthase inhibitors identified by a high-throughput screen. These compounds possess defined structure-activity relationships and we present crystal structures of cyclic GMP-AMP synthase, double-stranded DNA, and inhibitors within the enzymatic active site. We find that a chemically improved member, RU.521, is active and selective in cellular assays of cyclic GMP-AMP synthase-mediated signaling and reduces constitutive expression of interferon in macrophages from a mouse model of Aicardi-Goutières syndrome. RU.521 will be useful toward understanding the biological roles of cyclic GMP-AMP synthase and can serve as a molecular scaffold for development of future autoimmune therapies., Upon DNA binding cyclic GMP-AMP synthase (cGAS) produces a cyclic dinucleotide, which leads to the upregulation of inflammatory genes. Here the authors develop small molecule cGAS inhibitors, functionally characterize them and present the inhibitor and DNA bound cGAS crystal structures, which will facilitate drug development.

Published
2017
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10. Publisher Correction: Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice

Author

Vincent, Jessica, primary, Adura, Carolina, additional, Gao, Pu, additional, Luz, Antonio, additional, Lama, Lodoe, additional, Asano, Yasutomi, additional, Okamoto, Rei, additional, Imaeda, Toshihiro, additional, Aida, Jumpei, additional, Rothamel, Katherine, additional, Gogakos, Tasos, additional, Steinberg, Joshua, additional, Reasoner, Seth, additional, Aso, Kazuyoshi, additional, Tuschl, Thomas, additional, Patel, Dinshaw J., additional, Glickman, J. Fraser, additional, and Ascano, Manuel, additional

Published
2017
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11. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice

Author

Vincent, Jessica, primary, Adura, Carolina, additional, Gao, Pu, additional, Luz, Antonio, additional, Lama, Lodoe, additional, Asano, Yasutomi, additional, Okamoto, Rei, additional, Imaeda, Toshihiro, additional, Aida, Jumpei, additional, Rothamel, Katherine, additional, Gogakos, Tasos, additional, Steinberg, Joshua, additional, Reasoner, Seth, additional, Aso, Kazuyoshi, additional, Tuschl, Thomas, additional, Patel, Dinshaw J., additional, Glickman, J. Fraser, additional, and Ascano, Manuel, additional

Published
2017
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12. Publisher Correction: Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice

Author

Kazuyoshi Aso, Dinshaw J. Patel, Jessica Vincent, Rei Okamoto, Pu Gao, Aida Jumpei, Tasos Gogakos, Thomas Tuschl, Manuel Ascano, J. Fraser Glickman, Carolina Adura, Antonio Luz, L. Lama, Katherine Rothamel, Toshihiro Imaeda, Joshua Steinberg, Seth A. Reasoner, and Asano Yasutomi

Subjects
0301 basic medicine, Multidisciplinary, business.industry, Science, General Physics and Astronomy, General Chemistry, Biology, Small molecule, Molecular biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 030104 developmental biology, Text mining, Interferon, medicine, lcsh:Q, business, lcsh:Science, medicine.drug
Abstract

The previously published version of this Article contained errors in Fig. 6. In panel h the units of the x axis were incorrectly given as mM and should have been given as µM. Also, the IC50s for RU.365, RU.332 and RU.521 within panel h were incorrectly given as mM and should have been given as µM. These errors have been corrected in both the PDF and HTML versions of the Article.

Published
2017
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13. Correction to Melanin-Concentrating Hormone Receptor 1 Antagonists Lacking an Aliphatic Amine: Synthesis and Structure–Activity Relationships of Novel 1-(Imidazo[1,2-a]pyridin-6-yl)pyridin-2(1H)-one Derivatives

Author

Igawa, Hideyuki, primary, Takahashi, Masashi, additional, Kakegawa, Keiko, additional, Kina, Asato, additional, Ikoma, Minoru, additional, Aida, Jumpei, additional, Yasuma, Tsuneo, additional, Kawata, Yayoi, additional, Ashina, Shuntaro, additional, Yamamoto, Syunsuke, additional, Kundu, Mrinalkanti, additional, Khamrai, Uttam, additional, Hirabayashi, Hideki, additional, Nakayama, Masaharu, additional, Nagisa, Yasutaka, additional, Kasai, Shizuo, additional, and Maekawa, Tsuyoshi, additional

Published
2016
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14. Melanin-Concentrating Hormone Receptor 1 Antagonists Lacking an Aliphatic Amine: Synthesis and Structure–Activity Relationships of Novel 1-(Imidazo[1,2-a]pyridin-6-yl)pyridin-2(1H)-one Derivatives

Author

Igawa, Hideyuki, primary, Takahashi, Masashi, additional, Kakegawa, Keiko, additional, Kina, Asato, additional, Ikoma, Minoru, additional, Aida, Jumpei, additional, Yasuma, Tsuneo, additional, Kawata, Yayoi, additional, Ashina, Shuntaro, additional, Yamamoto, Syunsuke, additional, Kundu, Mrinalkanti, additional, Khamrai, Uttam, additional, Hirabayashi, Hideki, additional, Nakayama, Masaharu, additional, Nagisa, Yasutaka, additional, Kasai, Shizuo, additional, and Maekawa, Tsuyoshi, additional

Published
2016
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15. Design, Synthesis, and Evaluation of [ 18 F]T-914 as a Novel Positron-Emission Tomography Tracer for Lysine-Specific Demethylase 1.

Author

Matsuda S, Hattori Y, Matsumiya K, McQuade P, Yamashita T, Aida J, Sandiego CM, Gouasmat A, Carroll VM, Barret O, Tamagnan G, Koike T, and Kimura H

Subjects
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Animals, Female, Fluorine Radioisotopes, Gene Expression Regulation drug effects, Hepatocytes metabolism, Humans, Macaca fascicularis, Male, Positron-Emission Tomography, Drug Delivery Systems, Drug Design, Histone Demethylases chemistry, Histone Demethylases metabolism
Abstract

Histone methylation is associated with the pathophysiology of neurodevelopmental disorders. Lysine-specific demethylase 1 (LSD1) catalyzes histone demethylation in a flavin adenine dinucleotide (FAD)-dependent manner. Thus, inhibiting LSD1 enzyme activity could offer a novel way to treat neurodevelopmental disorders. Assessing LSD1 target engagement using positron-emission tomography (PET) imaging could aid in developing therapeutic LSD1 inhibitors. In this study, PET probes based on 4-(2-aminocyclopropyl)benzamide derivatives that bind irreversibly to FAD found in LSD1 were examined. By optimizing the profiles of brain penetrance and brain-penetrant metabolites, T-914 ( 1g ) was identified as a suitable PET tracer candidate. PET studies in nonhuman primates demonstrated that [ 18 F] 1g had heterogeneous brain uptake, which corresponded to known LSD1 expression levels. Moreover, brain uptake of [ 18 F] 1g was reduced by coadministration of unlabeled 1g , demonstrating blockable binding. These data suggest that [ 18 F] 1g warrants further investigation as a potential PET tracer candidate for assessing target engagement of LSD1.

Published
2021
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16. Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2 H -benzo[ b ][1,4]oxazin-6-yl Moiety.

Author

Ikeda S, Sugiyama H, Tokuhara H, Murakami M, Nakamura M, Oguro Y, Aida J, Morishita N, Sogabe S, Dougan DR, Gay SC, Qin L, Arimura N, Takahashi Y, Sasaki M, Kamada Y, Aoyama K, Kimoto K, and Kamata M

Subjects
Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Models, Molecular, Molecular Structure, Monoacylglycerol Lipases metabolism, Oxazines chemistry, Spiro Compounds chemical synthesis, Spiro Compounds chemistry, Structure-Activity Relationship, Drug Design, Enzyme Inhibitors pharmacology, Monoacylglycerol Lipases antagonists & inhibitors, Oxazines pharmacology, Spiro Compounds pharmacology
Abstract

The therapeutic potential of monoacylglycerol lipase (MAGL) inhibitors in central nervous system-related diseases has attracted attention worldwide. However, the availability of reversible-type inhibitor is still limited to clarify the pharmacological effect. Herein, we report the discovery of novel spiro chemical series as potent and reversible MAGL inhibitors with a different binding mode to MAGL using Arg57 and His121. Starting from hit compound 1 and its co-crystal structure with MAGL, structure-based drug discovery (SBDD) approach enabled us to generate various spiro scaffolds like 2a (azetidine-lactam), 2b (cyclobutane-lactam), and 2d (cyclobutane-carbamate) as novel bioisosteres of 3-oxo-3,4-dihydro-2 H -benzo[ b ][1,4]oxazin-6-yl moiety in 1 with higher lipophilic ligand efficiency (LLE). Optimization of the left hand side afforded 4f as a promising reversible MAGL inhibitor, which showed potent in vitro MAGL inhibitory activity (IC 50 6.2 nM), good oral absorption, blood-brain barrier penetration, and significant pharmacodynamic changes (2-arachidonoylglycerol increase and arachidonic acid decrease) at 0.3-10 mg/kg, po. in mice.

Published
2021
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