研究者詳細 - 加来田　博貴

論文 - 加来田　博貴

分割表示 81 件中 1 - 20 件目／全件表示 >>

Structural basis for the full and partial agonist activities of retinoid X receptor α ligands with an iso-butoxy and an isopropyl group. 国際誌

Daisuke Imai, Nobutaka Numoto, Hiroaki Tokiwa, Hiroki Kakuta, Nobutoshi Ito

Biochemical and biophysical research communications 734 150617 - 150617 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Retinoid X receptors (RXRs) belong to a retinoid-binding subgroup of the nuclear receptor family, and their synthetic agonists have been developed as therapeutics for glucose and lipid metabolism, inflammation, and inflammatory bowel disease, although RXR agonists could cause side effects such as hypothyroidism, hypertriglyceridemia, and hepatomegaly. We previously reported novel full and partial agonists, NEt-3IB and NEt-4IB, which reduce the side effects, but the molecular basis of their different activity was not clear. In this study, we report the crystal structures of the ligand-binding domain of human RXRα complexed with NEt-3IB and NEt-4IB. Detailed comparisons of the two structures showed that the full agonist, NEt-3IB, is more stably accommodated in the ligand-binding pocket due to the interactions of the bulky iso-butoxy group with helices 5 and 7. The stabilization of these helices led to the stabilization of helix 12, which is important for formation of the coactivator-binding site. The structures shed light on the novel mechanism of the regulation of RXR activity through the interaction between the bound agonist and helix 7, an interaction that was not previously considered important.

DOI： 10.1016/j.bbrc.2024.150617

PubMed

researchmap

Simple Fluorescence Labeling Method Enables Detection of Intracellular Distribution and Expression Level of Retinoid X Receptors 査読

Yukina Tanaka, Michiko Fujihara, Yuta Takamura, Mayu Kawasaki, Shogo Nakano, Makoto Makishima, Hiroki Kakuta

ACS Medicinal Chemistry Letters 2024年5月

Direct evaluation of polarity of the ligand binding pocket in retinoid X receptor using a fluorescent solvatochromic agonist. 査読国際誌

Kizuku Miura, Michiko Fujihara, Masaki Watanabe, Yuta Takamura, Mayu Kawasaki, Shogo Nakano, Hiroki Kakuta

Bioorganic & medicinal chemistry letters 96 129536 - 129536 2023年10月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

High selectivity of small-molecule drug candidates for their target molecule is important to minimize potential side effects. One factor that contributes to the selectivity is the internal polarity of the ligand-binding pocket (LBP) in the target molecule, but this is difficult to measure. Here, we first confirmed that the retinoid X receptor (RXR) agonist 6-(ethyl(1-isobutyl-2-oxo-4-(trifluoromethyl)-1,2-dihydroquinolin-7-yl)amino)nicotinic acid (NEt-iFQ, 1) exhibits fluorescence solvatochromism, i.e., its Stokes shift depends on the polarity of the solvent, and then we utilized this property to directly measure the internal polarity of the RXRα-LBP. The Stokes shift of 1 when bound to the RXRα-LBP corresponded to that of 1 in chloroform solution. This finding is expected to be helpful for designing RXR-selective ligands. A similar approach should be appliable to evaluate the internal polarity of the LBPs of other receptors.

DOI： 10.1016/j.bmcl.2023.129536

PubMed

researchmap

Ligand Screening System for the RXRα Heterodimer Using the Fluorescence RXR Agonist CU-6PMN 査読

Mayu Kawasaki, Tomoharu Motoyama, Shoya Yamada, Masaki Watanabe, Michiko Fujihara, Akira Kambe, Shogo Nakano, Hiroki Kakuta, Sohei Ito

ACS Medicinal Chemistry Letters 14 ( 3 ) 291 - 296 2023年2月

Structural characterization of 1,3-bis-tert-butyl monocyclic benzene derivatives with agonistic activity towards retinoid X receptor alpha. 査読国際誌

Susumu Kodama, Shuzo Matsumoto, Yuta Takamura, Michiko Fujihara, Masaki Watanabe, Atsushi Ono, Hiroki Kakuta

Toxicology letters 373 76 - 83 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Retinoid X receptor alpha (RXRα) plays pivotal roles in multiple biological processes, but limited information is available on the structural features of chemicals that show low affinity for RXRα, but nevertheless cause significant activation, though these may represent a human health hazard. We recently discovered that several industrial chemicals having 1,3-bis-tert-butylbenzene as a common chemical structure exhibit agonistic activity towards rat RXRα. In this study, we explored the structure-activity relationship of 1,3-bis-tert-butyl monocyclic benzene derivatives for RXRα activation by means of in vitro and in silico analyses. The results indicate that a bulky substituent at the 5-position is favorable for agonistic activity towards human RXRα. Since 1,3-bis-tert-butyl monocyclic benzene derivatives with bulky hydrophobic moieties differ structurally from known RXRα ligands such as 9-cis-retinoic acid and bexarotene, our findings may be helpful for the development of structural alerts in the safety evaluation of industrial chemicals for RXRα-based toxicity to living organisms.

DOI： 10.1016/j.toxlet.2022.11.003

PubMed

researchmap

Analysis of absorption-enhancing mechanisms for combinatorial use of spermine with sodium taurocholate in Caco-2 cells. 査読国際誌

Masato Maruyama, Yohei Nishida, Hironori Tanaka, Takako Minami, Ken-Ichi Ogawara, Masateru Miyake, Yuta Takamura, Hiroki Kakuta, Kazutaka Higaki

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 180 332 - 343 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Previously, we reported that the combined use of spermine (SPM) and sodium taurocholate (STC) (SPM-STC) significantly improves the oral absorption of rebamipide (BCS class IV) and pulmonary absorption of interferon-α without any harmful histopathological changes in the gastrointestinal tract and lungs, respectively. In the present study, we examined the effect of SPM-STC on the transport of fluorescein isothiocyanate-labeled dextrans (FDs) across Caco-2 cell monolayers and attempted to clarify the mechanisms underlying the transport enhancement caused by SPM-STC. SPM-STC were found to significantly enhance the transport of FDs, while the treatment with SPM-STC was not harmful, and the decrease in transepithelial electrical resistance was transient and reversible. The voltage-clamp study clearly indicated that the opening of the paracellular route could be mainly responsible for the enhanced transport of FD-4. As for the mechanisms, it was found that SPM-STC caused a significant increase in membrane fluidity, which would lead to the enhanced transport of small-molecule drugs such as rebamipide. Since SPM-STC increased intracellular Ca2+ via Ca2+ uptake through Ca2+ channels and Ca2+ release from the endoplasmic reticulum stimulated by the IP3 pathway, the subsequent possible activation of the MLCK signaling pathway would have led to the contraction of the actin-myosin ring. The rearrangement of tight junction-constituting proteins induced through the MAPK pathway has also been suggested as a possible mechanism for opening tight junctions. Claudin-4, a key protein constituting the tight junction, merged with F-actin along with the plasma membrane, was significantly decreased, which would be at least partial structural evidence for the tight-junction opening.

DOI： 10.1016/j.ejpb.2022.10.020

PubMed

researchmap

Teratogenicity and Fetal-Transfer Assessment of the Retinoid X Receptor Agonist Bexarotene. 査読国際誌

Yuta Takamura, Izumi Kato, Manami Fujita-Takahashi, Midori Azuma-Nishii, Masaki Watanabe, Rui Nozaki, Masaru Akehi, Takanori Sasaki, Hiroyuki Hirano, Hiroki Kakuta

ACS pharmacology & translational science 5 ( 9 ) 811 - 818 2022年9月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Bexarotene, a retinoid X receptor (RXR) agonist, is used to treat cutaneous T-cell lymphoma, and drug repositioning research has also been reported, despite warnings of teratogenicity. However, fetal transfer of bexarotene and its effect on rat fetal bone formation have not been examined. In this study, we conducted a detailed teratogenicity and fetal transferability assessment of bexarotene in rats. Repeated administration of bexarotene during pregnancy caused marked fetal atrophy and bone dysplasia. Although fetal transfer was not detectable by dynamic imaging of [11C]bexarotene by means of positron emission tomography, transfer to the fetus was confirmed by using a gamma counter. Similar levels were found in mother and fetus. In addition, we found that bexarotene was accumulated in the placenta. These findings will be useful for the toxicity assessment of bexarotene as well as for drug discovery research targeting RXR agonists, which are expected to have therapeutic effects in various diseases.

DOI： 10.1021/acsptsci.2c00126

PubMed

researchmap

Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo. 査読国際誌

Negar Khazan, Kyu Kwang Kim, Jeanne N Hansen, Niloy A Singh, Taylor Moore, Cameron W A Snyder, Ravina Pandita, Myla Strawderman, Michiko Fujihara, Yuta Takamura, Ye Jian, Nicholas Battaglia, Naohiro Yano, Yuki Teramoto, Leggy A Arnold, Russell Hopson, Keshav Kishor, Sneha Nayak, Debasmita Ojha, Ashoke Sharon, John M Ashton, Jian Wang, Michael T Milano, Hiroshi Miyamoto, David C Linehan, Scott A Gerber, Nada Kawar, Ajay P Singh, Erdem D Tabdanov, Nikolay V Dokholyan, Hiroki Kakuta, Peter W Jurutka, Nina F Schor, Rachael B Rowswell-Turner, Rakesh K Singh, Richard G Moore

Journal of Medicinal Chemistry 65 ( 8 ) 6039 - 6055 2022年4月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize.

DOI： 10.1021/acs.jmedchem.1c01878

PubMed

researchmap

Increased Molecular Flexibility Widens the Gap between Ki and Kd values in Screening for Retinoid X Receptor Modulators 査読

Masaki Watanabe, Mariko Nakamura-Nakayama, Michiko Fujihara, Mayu Kawasaki, Shogo Nakano, Hiroki Kakuta

ACS Medicinal Chemistry Letters 13 ( 2 ) 211 - 217 2022年1月

A Retinoid X Receptor Agonist Directed to the Large Intestine Ameliorates T-Cell-Mediated Colitis in Mice 査読国際誌

Ryohtaroh Matsumoto, Daisuke Takahashi, Masaki Watanabe, Shunsuke Nakatani, Yuta Takamura, Yuji Kurosaki, Hiroki Kakuta, Koji Hase

Frontiers in Pharmacology 12 715752 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

Retinoid X receptor (RXR) is a nuclear receptor that heterodimerizes with several nuclear receptors, integrating ligand-mediated signals across the heterodimers. Synthetic RXR agonists have been developed to cure certain inflammatory diseases, including inflammatory bowel diseases (IBDs). However, pre-existing RXR agonists, which are lipophilic and readily absorbed in the upper intestine, cause considerable adverse effects such as hepatomegaly, hyperlipidemia, and hypothyroidism. To minimize these adverse effects, we have developed an RXR agonist, NEt-3IB, which has lipophilic and thus poorly absorptive properties. In this study, we evaluated the effects of NEt-3IB in an experimental murine colitis model induced through the adoptive transfer of CD45RB<sup>high</sup>CD4<sup>+</sup> T cells. Pharmacokinetic studies demonstrated that the major portion of NEt-3IB was successfully delivered to the large intestine after oral administration. Notably, NEt-3IB treatment suppressed the development of T cell-mediated chronic colitis, as indicated by improvement of wasting symptoms, inflammatory infiltration, and mucosal hyperplasia. The protective effect of NEt-3IB was mediated by the suppression of IFN-γ-producing Th1 cell expansion in the colon. In conclusion, NEt-3IB, a large intestine-directed RXR agonist, is a promising drug candidate for IBDs.

DOI： 10.3389/fphar.2021.715752

researchmap

Creation of Fluorescent RXR Antagonists Based on CBTF-EE and Application to a Fluorescence Polarization Binding Assay 査読

Maho Takioku, Yuta Takamura, Michiko Fujihara, Masaki Watanabe, Shoya Yamada, Mayu Kawasaki, Sohei Ito, Shogo Nakano, Hiroki Kakuta

ACS Medicinal Chemistry Letters 2021年6月

In Vivo Receptor Visualization and Evaluation of Receptor Occupancy with Positron Emission Tomography 招待査読

Yuta Takamura, Hiroki Kakuta

Journal of Medicinal Chemistry 64 ( 9 ) 5226 - 5251 2021年5月

Discovery of a “Gatekeeper” Antagonist that Blocks Entry Pathway to Retinoid X Receptors (RXRs) without Allosteric Ligand Inhibition in Permissive RXR Heterodimers 査読

Masaki Watanabe, Michiko Fujihara, Tomoharu Motoyama, Mayu Kawasaki, Shoya Yamada, Yuta Takamura, Sohei Ito, Makoto Makishima, Shogo Nakano, Hiroki Kakuta

Journal of Medicinal Chemistry 64 ( 1 ) 430 - 439 2021年1月

Fluorescence properties of retinoid X receptor antagonist NEt-SB 査読

Shoya Yamada, Yuta Takamura, Michiko Fujihara, Mayu Kawasaki, Sohei Ito, Shogo Nakano, Hiroki Kakuta

Bioorganic & Medicinal Chemistry Letters 31 127666 - 127666 2021年1月

A Retinoid X Receptor Agonist Directed to the Large Intestine Ameliorates T-Cell-Mediated Colitis in Mice. 査読国際誌

Ryohtaroh Matsumoto, Daisuke Takahashi, Masaki Watanabe, Shunsuke Nakatani, Yuta Takamura, Yuji Kurosaki, Hiroki Kakuta, Koji Hase

Frontiers in pharmacology 12 715752 - 715752 2021年

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Retinoid X receptor (RXR) is a nuclear receptor that heterodimerizes with several nuclear receptors, integrating ligand-mediated signals across the heterodimers. Synthetic RXR agonists have been developed to cure certain inflammatory diseases, including inflammatory bowel diseases (IBDs). However, pre-existing RXR agonists, which are lipophilic and readily absorbed in the upper intestine, cause considerable adverse effects such as hepatomegaly, hyperlipidemia, and hypothyroidism. To minimize these adverse effects, we have developed an RXR agonist, NEt-3IB, which has lipophilic and thus poorly absorptive properties. In this study, we evaluated the effects of NEt-3IB in an experimental murine colitis model induced through the adoptive transfer of CD45RBhighCD4+ T cells. Pharmacokinetic studies demonstrated that the major portion of NEt-3IB was successfully delivered to the large intestine after oral administration. Notably, NEt-3IB treatment suppressed the development of T cell-mediated chronic colitis, as indicated by improvement of wasting symptoms, inflammatory infiltration, and mucosal hyperplasia. The protective effect of NEt-3IB was mediated by the suppression of IFN-γ-producing Th1 cell expansion in the colon. In conclusion, NEt-3IB, a large intestine-directed RXR agonist, is a promising drug candidate for IBDs.

DOI： 10.3389/fphar.2021.715752

PubMed

researchmap

Convenient Retinoid X Receptor Binding Assay Based on Fluorescence Change of the Antagonist NEt-C343. 査読

Hiroki Kakuta

Journal of Medicinal Chemistry 64 ( 1 ) 861 - 870 2020年12月

担当区分：最終著者,　責任著者掲載種別：研究論文（学術雑誌）出版者・発行元：American Chemical Society (ACS)

Retinoid X receptor (RXR) modulators (rexinoids) are considered to have therapeutic potential for multiple diseases, such as Alzheimer's disease and Parkinson's disease. To overcome various disadvantages of prior screening methods, we previously developed an RXR binding assay using a fluorescent RXR ligand, CU-6PMN (4). However, this ligand binds not only at the ligand-binding domain (LBD) but also at the dimer-dimer interface of hRXRα. Here, we present a new fluorescent RXR antagonist 6-[N-ethyl-N-(5-isobutoxy-4-isopropyl-2-(11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carboxamido)phenyl)amino]nicotinic acid (NEt-C343, 7), which emits strong fluorescence only when bound to the RXR-LBD. It allows us to perform a rapid, simple, and nonhazardous binding assay that does not require bound/free separation and uses a standard plate reader. The obtained Ki values of known compounds were correlated with the Ki values obtained using the standard [³H]9cis-retinoic acid assay. This assay should be useful for drug discovery as well as for research on endocrine disruptors, functional foods, and natural products.

DOI： 10.1021/acs.jmedchem.0c01883

PubMed

researchmap

Paclitaxel and Sorafenib: The Effective Combination of Suppressing the Self-Renewal of Cancer Stem Cells 査読国際誌

Hend M Nawara, SAID M AFIFY, Ghmkin Hassan, Maram H. Zahra, Marwa Atallah, Hager Mansour, Hagar A. Abu Quora, Md Jahangir Alam, Amira Osman, Hiroki Kakuta, Hiroki Hamada, Akimasa Seno, Masaharu Seno

Cancers 12 ( 6 ) 1360 - 1360 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：{MDPI} {AG}

"Combination therapy", which is a treatment modality combining two or more therapeutic agents, is considered a cornerstone of cancer therapy. The combination of anticancer drugs, of which functions are different from the other, enhances the efficiency compared to the monotherapy because it targets cancer cells in a synergistic or an additive manner. In this study, the combination of paclitaxel and sorafenib in low concentration was evaluated to target cancer stem cells, miPS-BT549cmP and miPS-Huh7cmP cells, developed from mouse induced pluripotent stem cells. The synergistic effect of paclitaxel and sorafenib on cancer stem cells was assessed by the inhibition of proliferation, self-renewal, colony formation, and differentiation. While the IC50 values of paclitaxel and sorafenib were approximately ranging between 250 and 300 nM and between 6.5 and 8 µM, respectively, IC50 of paclitaxel reduced to 20 and 25 nM, which was not toxic in a single dose, in the presence of 1 µM sorafenib, which was not toxic to the cells. Then, the synergistic effect was further assessed for the potential of self-renewal of cancer stem cells by sphere formation ability. As a result, 1 µM of sorafenib significantly enhanced the effect of paclitaxel to suppress the number of spheres. Simultaneously, paclitaxel ranging in 1 to 4 nM significantly suppressed not only the colony formation but also the tube formation of the cancer stem cells in the presence of 1 µM sorafenib. These results suggest the combination therapy of paclitaxel and sorafenib in low doses should be an attractive approach to target cancer stem cells with fewer side effects.

DOI： 10.3390/cancers12061360

PubMed

researchmap

Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice 査読国際誌

Ikuo Kimura, Junki Miyamoto, Ryuji Ohue-Kitano, Keita Watanabe, Takahiro Yamada, Masayoshi Onuki, Ryo Aoki, Yosuke Isobe, Daiji Kashihara, Daisuke Inoue, Akihiko Inaba, Yuta Takamura, Satsuki Taira, Shunsuke Kumaki, Masaki Watanabe, Masato Ito, Fumiyuki Nakagawa, Junichiro Irie, Hiroki Kakuta, Masakazu Shinohara, Ken Iwatsuki, Gozoh Tsujimoto, Hiroaki Ohno, Makoto Arita, Hiroshi Itoh, Koji Hase

Science 367 ( 6481 ) 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

<jats:p>Antibiotics and dietary habits can affect the gut microbial community, thus influencing disease susceptibility. Although the effect of microbiota on the postnatal environment has been well documented, much less is known regarding the impact of gut microbiota at the embryonic stage. Here we show that maternal microbiota shapes the metabolic system of offspring in mice. During pregnancy, short-chain fatty acids produced by the maternal microbiota dictate the differentiation of neural, intestinal, and pancreatic cells through embryonic GPR41 and GPR43. This developmental process helps maintain postnatal energy homeostasis, as evidenced by the fact that offspring from germ-free mothers are highly susceptible to metabolic syndrome, even when reared under conventional conditions. Thus, our findings elaborate on a link between the maternal gut environment and the developmental origin of metabolic syndrome.</jats:p>

DOI： 10.1126/science.aaw8429

PubMed

researchmap

Reversal of established liver fibrosis by IC-2-engineered mesenchymal stem cell sheets 査読国際誌

Noriko Itaba, Yohei Kono, Kaori Watanabe, Tsuyoshi Yokobata, Hiroyuki Oka, Mitsuhiko Osaki, Hiroki Kakuta, Minoru Morimoto, Goshi Shiota

Scientific Reports 9 ( 1 ) 6841 - 6841 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media {LLC}

Chronic hepatitis viral infection, alcoholic intoxication, and obesity cause liver fibrosis, which progresses to decompensated liver cirrhosis, a disease for which medical demands cannot be met. Since there are currently no approved anti-fibrotic therapies for established liver fibrosis, the development of novel modalities is required to improve patient prognosis. In this study, we clarified the anti-fibrotic effects of cell sheets produced from human bone marrow-derived mesenchymal stem cells (MSCs) incubated on a temperature-sensitive culture dish with the chemical compound IC-2. Orthotopic transplantation of IC-2-engineered MSC sheets (IC-2 sheets) remarkably reduced liver fibrosis induced by chronic CCl4 administration. Further, the marked production of fibrolytic enzymes such as matrix metalloproteinase (MMP)-1 and MMP-14, as well as thioredoxin, which suppresses hepatic stellate cell activation, was observed in IC-2 sheets. Moreover, the anti-fibrotic effect of IC-2 sheets was much better than that of MSC sheets. Finally, knockdown experiments revealed that MMP-14 was primarily responsible for the reduction of liver fibrosis. Here, we show that IC-2 sheets could be a promising therapeutic option for established liver fibrosis.

DOI： 10.1038/s41598-019-43298-0

PubMed

researchmap

Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening. 査読国際誌

Shoya Yamada, Mayu Kawasaki, Michiko Fujihara, Masaki Watanabe, Yuta Takamura, Maho Takioku, Hiromi Nishioka, Yasuo Takeuchi, Makoto Makishima, Tomoharu Motoyama, Sohei Ito, Hiroaki Tokiwa, Shogo Nakano, Hiroki Kakuta

Journal of Medicinal Chemistry 62 ( 19 ) 8809 - 8818 2019年10月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2H-chromene-3-carboxylic acid (10, CU-6PMN) as a new fluorescent RXR agonist and developed a screening system of rexinoids using 10. Compound 10 was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay using 10 enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration.

DOI： 10.1021/acs.jmedchem.9b00995

PubMed

researchmap

　前のページ - 次のページ　

<加来田 博貴>

論文 - 加来田 博貴

<加来田　博貴>

論文 - 加来田　博貴