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中村 恵宣大学院医学系研究科 医科学専攻教授
研究活動情報
■ 受賞■ 論文
- 2026年08月, Mumps, 日本語地域一体型バイオバンクネットワークの共通基盤としてのSemantic Data Model(SDM)データウェアハウス: プロトタイプ設計と構築[査読有り]
- Springer Science and Business Media LLC, 2026年08月, BMC Urology[査読有り]研究論文(学術雑誌)
- Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with poor prognosis. Radiological pleuroparenchymal fibroelastosis (PPFE)-like findings, characterised by upper-lobe subpleural fibrosis, have been associated with worse outcome in IPF. While short leukocyte telomere length (LTL) is a recognised prognostic factor, its relationship with PPFE-like findings remains unclear. Methods We conducted a secondary analysis of an ongoing ILD cohort. IPF patients who underwent LTL measurement by quantitative PCR were classified into those with PPFE-like findings on high-resolution computed tomography (IPF/PPFE group) and those without such findings (IPF/usual interstitial pneumonia (UIP) group). Clinical characteristics, pulmonary function, telomere length and outcomes were compared. Age-adjusted LTL was evaluated using healthy controls. Prognostic factors were analysed using Cox regression. Results Among 179 IPF patients, 29 (16%) were assigned to the IPF/PPFE group. Compared to the IPF/UIP group (n=150), the IPF/PPFE group had lower body mass index and forced vital capacity, and significantly shorter LTL (p=0.002), with more patients below the 10th percentile of healthy controls (37.9% versus 12.0%). The IPF/PPFE group showed greater respiratory functional decline and higher mortality (65.5% versus 25.3%, p<0.001). In survival analysis, both PPFE-like findings and shortened LTL predicted worse outcomes; however, only PPFE-like findings remained independently associated with mortality in multivariate analysis. Conclusions IPF patients with PPFE-like findings constitute a distinct high-risk phenotype with shorter telomeres, accelerated progression, and poor prognosis. These findings highlight the clinical importance of recognising PPFE-like changes and telomere biology in IPF for risk stratification and emphasise the need for close monitoring and early intervention.European Respiratory Society (ERS), 2026年02月, ERJ Open Research, 12(4) (4), 01619 - 2025[査読有り]研究論文(学術雑誌)
- Abstract Background In patients diagnosed with AML, the implementation of leukemia gene testing in accordance with the ELN 2022 guidelines is of paramount importance for the stratification of prognoses, thereby facilitating the determination of optimal treatment strategies. Presently, comprehensive NGS-based methods are extensively employed for these classifications; however, implementing them globally, including in Japan, is constrained by several factors in daily clinical practice, such as cost per sample, turn-around time, and technical hurdles in quality control. Aims The objective of this study was to develop a cost-effective screening system capable of simultaneously screening multiple genes necessary for prognostic stratification of known targets. In the previous report, we selected three specific mutations: NPM1 mutations, FLT3-ITD mutations, and in-frame indel mutations in the bZIP domain of the CEBPA and developed assay panel. Since these mutations can be detected based on the length of DNA fragments, we adopted a multiplex fragment analysis method using a capillary electrophoresis sequencer (CES), which is cost-effective, highly sensitive and competent for various length of fragments. Methods We assessed the clinical performance of our assay panel measured 53 de novo AML patient samples (median age, 66 years; 36 males and 18 females). We employed the Sanger sequencing method as a control method. We detected the presence or absence of each mutation in the patient samples and calculated the percentage of agreement with the Sanger sequencing analysis. Clinical samples were obtained from Bioresource Center, Kobe University Hospital in accordance with the Declaration of Helsinki and under an approved Kobe University institutional research protocol (B240242). Results We confirmed 100% accuracy in comparison with the Sanger sequencing, which is the control method. The breakdown of mutations contained in clinical samples was as follows: 12 samples with NPM1 mutations, 11 samples with FLT3-ITD mutations, and 1 sample with in-frame indel mutations in the bZIP domain of the CEBPA, although the number of positive results includes duplicate calculations for samples containing multiple genetic mutations. For samples with a low mutation allelic ratio, the presence of mutations was confirmed, but they were below the sensitivity of the Sanger sequencing and could not be sequenced. Also, it was found that some FLT3-ITD mutation-positive samples contained ITDs of multiple sizes, with up to four different sizes (63, 69, 84, and 175 bp) of ITDs identified. Discussion In our previous report, it was demonstrated that the assay panel achieved 100% accuracy in agreement with Sanger sequencing when using simulated samples created by mixing synthetic genes with healthy human peripheral blood mononuclear cells, and detected mutations at a rate of 2.9%. In this clinical evaluation, utilizing real patient's cells, the method exhibited substantial agreement with the control method, thereby reinforcing its efficacy. It is noteworthy that even low-frequency variants were effectively identified. This case suggests that the assay panel may be useful for classifying the disease appropriately and determining treatment strategies in MDS with a tumor content of less than 20%, based on the 5th edition of the WHO classification. Furthermore, the test demonstrated an adequate capability to detect samples with multiple FLT3-ITDs of multiple sizes. Due to the inherent characteristics of NGS technology, the detection and annotation of these types of mutation remain intricate, and the design of primers that are specific to each mutation in qPCR is an arduous task. Conclusion The three-gene assay panel using our developed fragment analysis system in CES was able to detect the mutations of three key genes that can be used for minimum decision-making to perform prognosis stratification of de novo AML in accordance with current ELN guidelines in a manner that is rapid, highly sensitive, and cost-effective in comparison to NGS. Additionally, it can handle a wide range of mutation patterns without customization, a feature that distinguishes it from qPCR. We consider that this will enable rapid risk stratification prior to standard treatment to be provided to clinical settings in diverse regions around the world.American Society of Hematology, 2025年11月, Blood, 146(Supplement 1) (Supplement 1), 7854 - 7855研究論文(学術雑誌)
- Palladium-Catalyzed Coupling of Functionalized Primary and Secondary Amines with Aryl and Heteroaryl Halides: Two Ligands Suffice in Most Cases.We report our studies on the use of two catalyst systems, based on the ligands BrettPhos (1) and RuPhos (2), which provide the widest scope for Pd-catalyzed C-N cross-coupling reactions to date. Often low catalyst loadings and short reaction times can be used with functionalized aryl and heteroaryl coupling partners. The reactions are highly robust and can be set up and performed without the use of a glovebox. These catalysts should find wide application in the synthesis of complex molecules including pharmaceuticals, natural products and functional materials.2011年01月, Chemical science, 2(1) (1), 57 - 68, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 1,7- and 2,7-naphthyridine derivatives as potent and highly specific PDE5 inhibitors.Novel 1,7- and 2,7-naphthyridine derivatives, designed by the introduction of nitrogen atom into the phenyl ring of previously reported 4-aryl-1-isoquinolinone derivatives, were disclosed as a new structural class of potent and specific PDE5 inhibitors. Among them, 2,7-naphthyridine 4c showed potent PDE5 inhibition (IC(50)=0.23 nM) and one of the best PDE5 specificities against PDEs1-4,6 (>100,000-fold selective versus PDE1-4, 240-fold selective vs PDE6). This compound showed more potent relaxant effects on isolated rabbit corpus cavernosum (EC(30)=5.0 nM) than Sildenafil (EC(30)=8.7 nM). The compound 4c (T-0156) was selected for further biological and pharmacological evaluation of erectile dysfunction.2003年07月, Bioorganic & medicinal chemistry letters, 13(14) (14), 2341 - 5, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Construction of heterocyclic compounds by use of alpha-diazophosphonates: new one-pot syntheses of indoles and isocoumarins.[reaction: see text] alpha-Diazophosphonates, which have extremely useful properties from a synthetic point of view, are disclosed as 1,1-ambiphilic one-carbon building blocks for one-pot construction of various heterocyclic compounds. They are easily prepared and have higher stability by the effect of the phosphoryl group than corresponding alpha-diazocarbonyl compounds. Using this synthon, we have developed a novel, mild, and efficient synthetic method of 2,3-disubstituted indoles and 3,4-disubstituted isocoumarins.2002年07月, Organic letters, 4(14) (14), 2317 - 20, 英語, 国際誌研究論文(学術雑誌)
- Novel, potent, and selective phosphodiesterase 5 inhibitors: synthesis and biological activities of a series of 4-aryl-1-isoquinolinone derivatives.A novel class of potent and selective phosphodiesterase 5 (PDE5) inhibitors, 4-aryl-1-isoquinolinone derivatives, which have been designed by the comparison of the structure of cGMP and a previously reported 1-arylnaphthalene lignan, was disclosed. Among these compounds, methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate dihydrochloride (36a) exhibited potent PDE5 inhibitory activity (IC(50) = 1.0 nM) with high isozyme selectivities (IC(50) ratio: PDE1/PDE5 = 1300, PDE2/PDE5 > 10 000, PDE3/PDE5 > 10 000, PDE4/PDE5 = 4700, PDE6/PDE5 = 28). Compound 36a also showed the most potent relaxant effect on isolated rabbit corpus cavernosum (EC(30) = 7.9 nM). Compound 63 (T-1032), the sulfate form of 36a, was selected for further biological and pharmacological evaluation of erectile dysfunction.2001年06月, Journal of medicinal chemistry, 44(13) (13), 2204 - 18, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Characterization and effects of methyl-2- (4-aminophenyl)-1, 2-dihydro-1-oxo-7- (2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), a novel potent inhibitor of cGMP-binding cGMP-specific phosphodiesterase (PDE5).An isoquinolone derivative, methyl-2-(4-aminophenyl)-1, 2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4, 5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), was found to be a novel potent inhibitor of cyclic GMP (cGMP)-binding cGMP-specific phosphodiesterase (PDE5). We investigated the inhibitory effects of T-1032 on six PDE isozymes isolated from canine tissues. T-1032 specifically inhibited the hydrolysis of cGMP by PDE5 partially purified from canine lung, at a low concentration (IC(50) = 1.0 nM, K(i) = 1.2 nM), in a competitive manner. In contrast, the IC(50) values of T-1032 for PDE1, PDE2, PDE3, and PDE4 were more than 1 microM. T-1032 also inhibited PDE6 from canine retina with an IC(50) of 28 nM, which is of the same order of magnitude as the IC(50) of sildenafil. cGMP hydrolytic activities of two alternative splice variants of canine PDE5 expressed in COS-7 cells were inhibited by this compound to a similar extent. T-1032 increased the intracellular concentration of cGMP in cultured rat vascular smooth muscle cells in the presence and absence of C-type natriuretic peptide, an activator of membrane-bound guanylate cyclase, whereas the compound did not change cyclic AMP levels. These data indicated that T-1032, which belongs to a new structural class of PDE5 inhibitors, is a potent and selective PDE5 inhibitor. This compound may be useful in pharmacological studies to examine the role of a cGMP/PDE5 pathway in tissues.2000年11月, Biochemical pharmacology, 60(9) (9), 1333 - 41, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 1-Arylnaphthalene lignan: a novel scaffold for type 5 phosphodiesterase inhibitor.1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki, was disclosed as a new structural class of PDE5 inhibitors. The structural requirements for potent and specific PDE5 inhibition were revealed in a 1-arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro-3-[4-(2-hydroxyethyl)-1-piperazinylcarbon yl]-2-(methoxycarbonyl)naphthalene hydrochloride (27q) showed the most potent and specific inhibition (PDE5 inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 >16 000). It is noteworthy that 27q has the best selectivities against PDE isoforms among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3, 4-methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-ca rboxylate (35) (27q, EC50 = 0.10 microM; 35, EC50 = 0.20 microM) and was selected for further biological evaluation.1999年04月, Journal of medicinal chemistry, 42(7) (7), 1293 - 305, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Elsevier BV, 1996年04月, Tetrahedron Letters, 37(18) (18), 3129 - 3132[査読有り]研究論文(学術雑誌)
- Convenient syntheses of oligonucleotides linked to 5-deazaflavin coenzyme models at 3'-end. Incorporation of 5-deazaflavin to controlled pore glass (CPG) support.Using CPG support linked with 5-deazaflavin, the 5-deazaflavin modified oligodeoxynucleotides at 3'-end(ODN-dF1) were synthesized. The thermal stability of the duplex of ODN-dF1 with its complement was higher than that of oligonucleotide linked to 5-deazaflavin at 5'-end internucleotide linkage.1993年07月, Chemical & pharmaceutical bulletin, 41(7) (7), 1315 - 7, 英語, 国内誌[査読有り]研究論文(学術雑誌)
- 1993年04月, Chemical & pharmaceutical bulletin, 41(4) (4), 778 - 80, 英語, 国内誌Redox potential of oligonucleotide linked to 5-deazaflavin coenzyme model. Detection of hybrid formation by cyclic voltammometry.[査読有り]研究論文(学術雑誌)
- Hybiridization of Oligodeoxynucleotide with Redox Coenzyme Model; Synthesis and Properties of Thymidine Decamers Covalently Linked to 5-DeazaflavinModified thymidine decamers covalently linked to 5-deazaflavin derivatives through aminoalkyl spacer arm in the form of phosphoramidate bond, were prepared and characterized, Chemical and physical properties of the hydrid moleculeas are discussed.The Pharmaceutical Society of Japan, 1992年01月, Chemical & pharmaceutical bulletin, 40(1) (1), 291 - 293, 英語[査読有り]
- 2025年10月, 京大薬友会誌, 77, 16 - 17第10回薬学の未来を考える京都シンポジウム開催報告
- 医薬基盤・健康・栄養研究所と神奈川県立循環器呼吸器病センターは、官民研究開発投資拡大プログラム(PRISM)において、特発性肺線維症を対象に診療情報とオミックス情報(網羅的生体分子情報)を集積したデータベースを構築し、さらにそのデータにより患者を層別化し、データ駆動的に創薬ターゲットを探索するAIを開発している。PRISMでは創薬ターゲット探索AIのみならず、医療テキスト解析システム、知識の自動抽出、自動推論システム等の開発を行っており、これらを広く産学の研究者が利用できる仕組み(オープンプラットフォーム)を今年度中に運用開始予定である。公益社団法人 日本薬学会, 2022年08月01日, Medchem News, 32(3) (3), 119 - 123, 日本語
- 2022年, Pharm Tech Japan, 38(8) (8)デジタルトランスフォーメーションで変わる医療 臨床オミクスデータと人工知能を活用した革新的な創薬標的探索プラットフォームの構築~内閣府官民研究開発投資拡大プログラム(PRISM)での取り組み~
- コレステリルエステル転送タンパク質(Cholesteryl Ester Transfer Protein:CETP)阻害剤は、動脈硬化惹起性のLDLコレステロール(LDL-C)の低下、抗動脈硬化性のHDLコレステロール(HDL-C)の上昇という理想的な脂質制御が可能であり、新規の動脈硬化治療薬として期待できる。筆者らは、最適化研究において、「通常製剤での薬剤開発を意識したin vivo評価法の採用」および「in vitro評価法の改良」により、カルボン酸型化合物が優れた作用を有することを見出した。そして、カルボン酸型化合物のさらなる最適化により、臨床候補化合物TA-8995(obicetrapib)の創製に成功した。TA-8995は近年の臨床試験において、同クラスの化合物と比べて世界最強の作用を示した。公益社団法人 日本薬学会, 2019年08月01日, Medchem News, 29(3) (3), 128 - 132, 日本語
- 2017年09月, JAPIC NEWS, 401, 8 - 9, 日本語[招待有り]
- 2009年, Organometallic News, 58 - 59, 日本語MIT Buchwald研での研究とボストン留学生活[招待有り]
- 公益社団法人 日本薬学会, 2007年, ファルマシア, 43(6) (6), 577 - 578, 日本語
- 第65回日臨技近畿支部医学検査学会, 2026年09月, 日本語バイオバンクにおける臨床検査技師の役割口頭発表(一般)
- 第11回クリニカルバイオバンク学会シンポジウム, 2026年07月, 日本語バイオバンクにおける検査部連携の重要性ポスター発表
- 第47回染色体遺伝子検査基礎技術セミナー, 2026年06月, 日本語バイオバンクにおける臨床検査室の役割:ISO20387とISO15189の協奏口頭発表(招待・特別)
- 39th International Symposium on Technical Innovations in Laboratory Hematology, 2026年04月Impact of In Vitro Activated Coagulation as a Pre-Analytical Error on Coagulation and Fibrinolysis Test Resultsポスター発表
- 39th International Symposium on Technical Innovations in Laboratory Hematology, 2026年04月Machine Learning-Based Detection of In-Vitro Activated Coagulation Using APTT Clotting Curvesポスター発表
- 医療情報学連合大会論文集, 2025年11月, 日本語, (一社)日本医療情報学会【学術】バイオバンクにおける医療情報の二次利用 Semantic Data Model(SDM)に基づくデータウェアハウスの構築と利活用(Biobanks Leveraging Medical Information: Constructing and Utilizing a Semantic Data Model(SDM)-Based Data Warehouse)シンポジウム・ワークショップパネル(公募)
- 第53回日本Mテクノロジー学会大会, 2025年10月地域一体型仮想バイオバンクネットワークを志向した Semantic Data Model(SDM)データウェアハウスの設計と構築
- 医療検査と自動化, 2025年08月, 日本語, (一社)日本医療検査科学会自動搬送ラインを活用した検体処理プロセスの安定性評価とバイオリソース提供における品質担保
- 医療検査と自動化, 2025年08月, 日本語, (一社)日本医療検査科学会病院併設型バイオバンクにおける全血残余検体の収集・提供体制の評価
- 第10回クリニカルバイオバンク学会シンポジウム, 2025年07月ISO20387取得への歩みと今後の展望
- 日本臨床検査医学会誌, 2025年07月, 日本語, (一社)日本臨床検査医学会APTT凝固波形の機械学習による採血管内凝固検出アルゴリズムの構築
- 日本臨床検査医学会誌, 2025年07月, 日本語, (一社)日本臨床検査医学会Fib4 indexは関節リウマチ患者においてMTX継続率を予想する
- ISTH 2025 Congress, 2025年06月, 英語Accurate measurement of edoxaban concentration after reversal by andexanet alpha
- 日本臨床検査医学会誌, 2024年10月, 日本語, (一社)日本臨床検査医学会ニーズドリブン型バイオバンクにおける残余検体払出実績とタイムライン解析に基づく品質評価
- 第9回クリニカルバイオバンク学会シンポジウム, 2024年08月, 日本語, 東北大学星陵オーディトリアム / 東北メディカル・メガバンク機構ニーズドリブン型バイオバンクにおける残余血漿検体払出 実績と品質管理
- 第7回バイオバンク オープンフォーラム「バイオバンクが使われる ~あらためて利活用事例を考える~」, 2024年08月, 日本語利用者のニーズに応える “ニーズドリブン型”バイオバンクの取り組みについて口頭発表(招待・特別)
- 関西医薬品協会 令和6年度第1回研究開発推進会議, 2024年04月神戸大学医学部附属病院バイオリソースセンターの取り組み[招待有り]
- 日本薬学会年会要旨集(CD-ROM), 2019年CETP阻害薬としてのTA-8995(obicetrapib)の創薬
- メディシナルケミストリーシンポジウム講演要旨集, 2018年世界最強の作用を有するCETP阻害剤TA-8995(obicetrapib)の創製
- 日本薬学会年会要旨集, 2002年特異的PDE5阻害薬の合成研究
- 日本薬学会年会要旨集, 2001年特異的PDE5阻害作用を有するナフチリジノン誘導体の合成と薬理活性
- 18th International Congress of Heterocyclic Chemistry, 2001年Construction of Heterocyclic Compounds by Use of -Diazophosphonates: New One-pot Syntheses of Indole and Isocoumarin
- 日本薬学会年会要旨集, 2000年特異的PDE5阻害作用を有するイソキノロン誘導体の合成
- 日本薬学会年会要旨集, 1998年PDE V阻害作用を有する1-アリールナフタレンリグナンの合成
- 日本化学会講演予稿集, 1996年L-メントンを不斉源とする新規1,3-ベンゾオキサジノン不斉補助基の合成と反応
- 日本薬学会年会要旨集, 1992年酸化還元系補酵素モデル5-デアザフラビン修飾オリゴデオキシヌクレオチドの合成と性質
- コレステリルエステル輸送タンパク阻害剤としての三置換アミン化合物特願2008-535204, 2007年01月30日, 田辺三菱製薬株式会社, 特許第4943443号, 2012年03月09日特許権
- 医薬組成物特願2008-196568, 2008年07月30日, 田辺三菱製薬株式会社, 特開2009-051828, 2009年03月12日, 特許第4846769号, 2011年10月21日特許権
- 医薬組成物特願2008-196565, 2008年07月30日, 田辺三菱製薬株式会社, 特開2009-051827, 2009年03月12日, 特許第4834699号, 2011年09月30日特許権
- 医薬組成物特願2006-261889, 2006年09月27日, 田辺三菱製薬株式会社, 特開2007-119451, 2007年05月17日, 特許第4681526号, 2011年02月10日特許権
