Faculty Profiles - SHINDO NAOYA

Information

写真a

SHINDO NAOYA

Organization

Faculty of Pharmaceutical Sciences Department of Chemo-Pharmaceutical Sciences Lecturer

Contact information

Tel

0926426600

Profile

有機化学を基盤に、標的タンパク質と共有結合を作ってその機能を不可逆的に阻害するコバレントドラッグの創薬化学研究を進めています。コバレントドラッグが標的以外のオフターゲットタンパク質と結合すると毒性の発現につながる可能性があるため、標的選択性は非常に重要です。しかし、現在コバレントドラッグに用いられる求電子的反応基は本質的な反応性が比較的高く、選択性が必ずしも十分ではありません。そこで我々は、より安全に使用できるコバレントドラッグの開発を目指し、化合物を標的タンパク質と高選択的に反応させるための新たなケミストリーを開拓しています。

External link

Degree

Ph.D. in Pharmaceutical Sciences

Research Interests・Research Keywords

Research theme：In-cell organic chemistry for covalent drug discovery

Keyword：covalent drugs, medicinal chemistry, TCIs

Research period： 2013.6

Awards

2023年度日本薬学会メディシナルケミストリーシンポジウムBMC/BMCL賞

2023.11 日本薬学会医薬化学部会
2019年度有機合成化学協会九州山口支部優秀論文賞

2019.10 有機合成化学協会九州山口支部 Selective and reversible modification of kinase cysteines with chlorofluoroacetamides
EFMC-ASMC'19 Poster Prize

2019.9 The European Federation for Medicinal Chemistry
平成28年度日本薬学会メディシナルケミストリーシンポジウム優秀賞

2018.12 日本薬学会医薬化学部会

Papers

Expanding the Chemistry of Dihaloacetamides as Tunable Electrophiles for Reversible Covalent Targeting of Cysteines Reviewed International journal

#Daiki Yamane, #Ryo Tetsukawa, Naoki Zenmyo, Kaori Tabata, Yuya Yoshida, Naoya Matsunaga, Naoya Shindo, Akio Ojida

Journal of Medicinal Chemistry 66 ( 13 ) 9130 - 9146 2023.7

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Language：English Publishing type：Research paper (scientific journal)

DOI： https://doi.org/10.1021/acs.jmedchem.3c00737
Selective covalent targeting of SARS-CoV-2 main protease by enantiopure chlorofluoroacetamide Reviewed International journal

#Daiki Yamane, #Satsuki Onitsuka, @Suyong Re, #Hikaru Isogai, #Rui Hamada, #Tadanari Hiramoto, Eiji Kawanishi, @Kenji Mizuguchi, Naoya Shindo*, Akio Ojida*

Chemical Science 13 ( 10 ) 3027 - 3034 2022.2 （ ISSN:2041-6520 eISSN:2041-6539 ）

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1039/D1SC06596C

Web of Science

Scopus

PubMed
Bicyclobutane Carboxylic Amide as a Cysteine-Directed Strained Electrophile for Selective Targeting of Proteins Reviewed International journal

#Keisuke Tokunaga, #Mami Sato, @Keiko Kuwata, #Chizuru Miura, #Hirokazu Fuchida, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo, Naoya Shindo*, Akio Ojida*

Journal of the American Chemical Society 142 ( 43 ) 18522 - 18531 2020.10

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1021/jacs.0c07490

Other Link： https://pubs.acs.org/doi/10.1021/jacs.0c07490
Selective and reversible modification of kinase cysteines with chlorofluoroacetamides Reviewed International journal

Naoya Shindo, #Hirokazu Fuchida, #Mami Sato, Kosuke Watari, #Tomohiro Shibata, @Keiko Kuwata, #Chizuru Miura, #Kei Okamoto, #Yuji Hatsuyama, #Keisuke Tokunaga, Seiichi Sakamoto, Satoshi Morimoto, Yoshito Abe, Mitsunori Shiroishi, Jose M. M. Caaveiro, Tadashi Ueda, @Tomonori Tamura, Naoya Matsunaga, #Takaharu Nakao, Satoru Koyanagi, Shigehiro Ohdo, @Yasuchika Yamaguchi, @Itaru Hamachi, Mayumi Ono, Akio Ojida

Nature Chemical Biology 15 ( 3 ) 250 - 258 2019.1

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Language：English Publishing type：Research paper (scientific journal)

DOI： https://doi.org/10.1038/s41589-018-0204-3
Inhibition of dynamin-related protein 1-filamin interaction improves systemic glucose metabolism

Kato, Y; Ariyoshi, K; Nohara, Y; Matsunaga, N; Shimauchi, T; Shindo, N; Nishimura, A; Mi, XY; Kim, SG; Ide, T; Kawanishi, E; Ojida, A; Nakashima, N; Mori, Y; Nishida, M

BRITISH JOURNAL OF PHARMACOLOGY 181 ( 21 ) 4328 - 4347 2024.7 （ ISSN:0007-1188 eISSN:1476-5381 ）

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Language：English

DOI： 10.1111/bph.16487

Web of Science

PubMed
Chemoselective lysine-reactive electrophiles for covalent targeting of proteins

Shindo Naoya, Tanaka Yudai, Tanigawa Atsuya, Ojida Akio

MEDCHEM NEWS 34 ( 2 ) 88 - 92 2024.5 （ ISSN:24328618 eISSN:24328626 ）

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Language：Japanese Publisher：The Pharmaceutical Society of Japan

Covalent drugs exert potent and sustained pharmacological efficacy through irreversible inhibition of the target protein. While cysteine-targeting covalent drug discovery has been a powerful strategy, the target scope is limited due to the low abundance of cysteines in the proteome. Covalent targeting of lysines would greatly expand the opportunity. However, the scarcity of aminophilic electrophiles with high chemoselectivity and stability under live cell conditions prevents progress. Here, we disclose 2-cyanoarenesulfonamides (CNS) as novel aminophilic warheads. CNS exhibits highly chemoselective and tunable reactivity toward amines through a novel mechanism involving ring-chain tautomerism. We designed CNS-based covalent inhibitors targeting Lys58 of heat shock protein 90 (Hsp90) . The probes displayed good inhibitory activity and selectivity toward Hsp90 in live cells, demonstrating the utility of CNS as lysine-targeting electrophiles.

DOI： 10.14894/medchem.34.2_88

CiNii Research
Chemistry of Covalent Drugs: Chemical Reactions with Endogenous Proteins in Live Cells

Shindo Naoya, Ojida Akio

Journal of Synthetic Organic Chemistry, Japan 82 ( 1 ) 50 - 62 2024.1 （ ISSN:00379980 eISSN:18836526 ）

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Language：Japanese Publisher：The Society of Synthetic Organic Chemistry, Japan

<p>Covalent drugs render potent and durable activity by chemical modification of the endogenous target protein under live cell conditions. To maximize the pharmacological efficay while alleviating the risk of toxicity arising from non-specific off-target reactions, current covalent drug discovery focuses on the development of targeted covalent inhibitors (TCIs). In the design of TCIs, an electrophilic reactive group (warhead) is strategically incorporated onto a reversible ligand of the target protein to facillitate specific covalent engagement. Various aspects of warheads, such as intrinsic reactivity, chemoselectivity, reaction mechanism, and reversibility of the covalent engagement, would affect the target selectivity of TCIs. While covalent targeting of cysteines by acrylamide-type Michael acceptors have been the most successful strategy in covalent drug discovery, a wide array of novel warheads have been devised and tested for designing TCIs in recent years. This review provides an overview of chemistry for selective covalent targeting of endogenous proteins under live cell conditions and its applications in TCI designs.</p>

DOI： 10.5059/yukigoseikyokaishi.82.50

Web of Science

Scopus

CiNii Research
Beneficial effects of a new neuroprotective compound in neuronal cells and MPTP-administered mouse model of Parkinsons disease

Kato, I; Ogawa, Y; Yakushiji, F; Ogura, J; Kobayashi, M; Shindo, N; Ichikawa, S; Maenaka, K; Sakaitani, M

CHEMICAL COMMUNICATIONS 59 ( 82 ) 12306 - 12309 2023.10 （ ISSN:1359-7345 eISSN:1364-548X ）

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Language：English Publisher：Chemical Communications

A new compound, a derivative of 3,4,5-trimethoxy-N-phenyl benzamide bearing an 8′′-methylimidazopyridine moiety, is found to demonstrate neuroprotective effects by preventing cell death caused by oxidative stress. The compound possesses high solubility and metabolic stability, and inhibits MPTP-induced effects in vivo, indicating high potential as a therapeutic drug for Parkinson's disease.

DOI： 10.1039/d3cc03069e

Web of Science

Scopus

PubMed
Inhibition of Tumor-Derived C-C Motif Chemokine Ligand 2 Expression Attenuates Tactile Allodynia in NCTC 2472 Fibrosarcoma-Inoculated Mice

Taniguchi, M; Yasukochi, S; Yamakawa, W; Tsurudome, Y; Tsuruta, A; Horiguchi, M; Ushijima, K; Yamashita, T; Shindo, N; Ojida, A; Matsunaga, N; Koyanagi, S; Ohdo, S

MOLECULAR PHARMACOLOGY 104 ( 2 ) 73 - 79 2023.8 （ ISSN:0026-895X eISSN:1521-0111 ）

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Language：English Publisher：Molecular pharmacology

Neuropathic pain associated with cancers is caused by tumor growth compressing and damaging nerves, which would also be enhanced by inflammatory factors through sensitizing nociceptor neurons. A troublesome hallmark symptom of neuropathic pain is hypersensitivity to innocuous stimuli, a condition known as "tactile allodynia", which is often refractory to NSAIDs and opioids. The involvement of chemokine CCL2 (monocyte chemoattractant protein-1) in cancer-evoked neuropathic pain is well established, but opinions remain divided as to whether CCL2 is involved in the production of tactile allodynia with tumor growth. In this study, we constructed Ccl2 knockout NCTC 2472 (Ccl2-KO NCTC) fibrosarcoma cells and conducted pain behavioral test using Ccl2-KO NCTC-implanted mice. Implantation of naïve NCTC cells around the sciatic nerves of mice produced tactile allodynia in the inoculated paw. Although the growth of Ccl2 KO NCTC-formed tumors was comparable to that of naïve NCTC-formed tumors, Ccl2-KO NCTC-bearing mice failed to show tactile pain hypersensitivity, suggesting the involvement of CCL2 in cancer-induced allodynia. Subcutaneous administration of controlled-release nanoparticles containing the CCL2 expression inhibitor NS-3-008 (1-benzyl-3-hexylguanidine) significantly attenuated tactile allodynia in naïve NCTC-bearing mice accompanied by a reduction of CCL2 content in tumor masses. Our present findings suggest that inhibition of CCL2 expression in cancer cells is a useful strategy to attenuate tactile allodynia induced by tumor growth. Development of a controlled-release system of CCL2 expression inhibitor may be a preventative option for the treatment of cancer-evoked neuropathic pain. SIGNIFICANCE STATEMENT: The blockade of chemokine/receptor signaling, particularly for C-C motif chemokine ligand 2 (CCL2) and its high-affinity receptor C-C chemokine receptor type 2 (CCR2), has been implicated to attenuate cancer-induced inflammatory and nociceptive pain. This study demonstrated that continuous inhibition of CCL2 production from cancer cells also prevents the development of tactile allodynia associated with tumor growth. Development of a controlled-release system of CCL2 expression inhibitor may be a preventative option for management of cancer-evoked tactile allodynia.

DOI： 10.1124/molpharm.123.000690

Web of Science

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PubMed
Beneficial effects of a new neuroprotective compound in neuronal cells and MPTP-administered mouse model of Parkinson's disease Reviewed International journal

Izumi Kato, Yudai Ogawa, Fumika Yakushiji, Jiro Ogura, Masaki Kobayashi, Naoya Shindo, Satoshi Ichikawa, Katsumi Maenaka, Masahiro Sakaitani

Chemical Communications 59 12306 - 12309 2023.8

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Language：English Publishing type：Research paper (scientific journal)

DOI： https://doi.org/10.1039/D3CC03069E
Inhibition of Tumor-Derived C-C Motif Chemokine Ligand 2 Expression Attenuates Tactile Allodynia in NCTC 2472 Fibrosarcoma-Inoculated Mice Reviewed International journal

#Marie Taniguchi, #Sai Yasukochi, #Wakaba Yamakawa, #Yuya Tsurudome, Akito Tsuruta, Michiko Horiguchi, Kentaro Ushijima, Tomohiro Yamashita, Naoya Shindo, Akio Ojida, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

Molecular Pharmacology 104 ( 2 ) 73 - 79 2023.8

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Language：English Publishing type：Research paper (scientific journal)

DOI： https://doi.org/10.1124/molpharm.123.000690
Expanding the Chemistry of Dihaloacetamides as Tunable Electrophiles for Reversible Covalent Targeting of Cysteines

Yamane, D; Tetsukawa, R; Zenmyo, N; Tabata, K; Yoshida, Y; Matsunaga, N; Shindo, N; Ojida, A

JOURNAL OF MEDICINAL CHEMISTRY 66 ( 13 ) 9130 - 9146 2023.7 （ ISSN:0022-2623 eISSN:1520-4804 ）

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Language：English Publisher：Journal of Medicinal Chemistry

The choice of an appropriate electrophile is crucial in the design of targeted covalent inhibitors (TCIs). In this report, we systematically investigated the glutathione (GSH) reactivity of various haloacetamides and the aqueous stability of their thiol adducts. Our findings revealed that dihaloacetamides cover a broad range of GSH reactivity depending on the combination of the halogen atoms and the structure of the amine scaffold. Among the dihaloacetamides, dichloroacetamide (DCA) exhibited slightly lower GSH reactivity than chlorofluoroacetamide (CFA). The DCA-thiol adduct is readily hydrolyzed under aqueous conditions, but it can stably exist in the solvent-sequestered binding pocket of the protein. These reactivity profiles of DCA were successfully exploited in the design of TCIs targeting noncatalytic cysteines of KRASG12C and EGFRL858R/T790M. These inhibitors exhibited strong antiproliferative activities against cancer cells. Our findings provide valuable insights for designing dihaloacetamide-based reversible covalent inhibitors.

DOI： 10.1021/acs.jmedchem.3c00737

Web of Science

Scopus

PubMed
Discovery of chlorofluoroacetamide-based covalent inhibitors for severe acute respiratory syndrome coronavirus 2 3CL protease Reviewed International journal

#Yuya Hirose, Naoya Shindo, Makiko Mori, #Satsuki Onitsuka, #Hikaru Isogai, #Rui Hamada, #Tadanari Hiramoto, #Jinta Ochi, Daisuke Takahashi, Tadashi Ueda, Jose M M Caaveiro, Yuya Yoshida, Shigehiro Ohdo, Naoya Matsunaga, @Shinsuke Toba, @Michihito Sasaki, @Yasuko Orba, @Hirofumi Sawa, @Akihiko Sato, Eiji Kawanishi, Akio Ojida

Journal of Medicinal Chemistry 65 ( 20 ) 13852 - 13865 2022.10 （ ISSN:0022-2623 eISSN:1520-4804 ）

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1021/acs.jmedchem.2c01081

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Fragment-Based Discovery of Irreversible Covalent Inhibitors of Cysteine Proteases Using Chlorofluoroacetamide Library Reviewed International journal

#Chizuru Miura, Naoya Shindo, #Kei Okamoto, @Keiko Kuwata, Akio Ojida

Chemical and Pharmaceutical Bulletin 68 ( 11 ) 1074 - 1081 2020.11

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1248/cpb.c20-00547
Selective Covalent Targeting of Mutated EGFR(T790M) with Chlorofluoroacetamide-Pyrimidines Reviewed International journal

#Mami Sato, #Hirokazu Fuchida, @Naoya Shindo, @Keiko Kuwata, #Keisuke Tokunaga, #Guo Xiao-Lin, #Ryo Inamori, #Keitaro Hosokawa, @Kosuke Watari, @Tomohiro Shibata, @Naoya Matsunaga, @Satoru Koyanagi, @Shigehiro Ohdo, @Mayumi Ono, @Akio Ojida

ACS Medicinal Chemistry Letters 11 ( 6 ) 1137 - 1144 2020.4

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1021/acsmedchemlett.9b00574
Hypoxia-induced interaction of filamin with Drp1 causes mitochondrial hyperfission-associated myocardinal senescence Reviewed International journal

Akiyuki Nishimura, Tsukasa Shimauchi, Tomohiro Tanaka, Kakeru Shimoda, Takashi Toyama, Naoyuki Kitajima, Tatsuya Ishikawa, Naoya Shindo, Takuro Numaga-Tomita, Satoshi Yasuda, Yoji Sato, Koichiro Kuwahara, Yoshito Kumagai, Takaaki Akaike, Tomomi Ide, Akio Ojida, Yasuo Mori, Motohiro Nishida

Science Signaling 11 ( 556 ) eaat5185 2018.11

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1126/scisignal.aat5185
コバレント阻害剤の標的特異性向上を目指した新規反応基の探索とEGFR阻害剤への応用 Invited

進藤直哉、王子田彰夫

27 ( 2 ) 92 - 99 2017.2

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Language：Japanese Publishing type：Research paper (scientific journal)
Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease Reviewed International journal

Naoya Matsunaga, Eriko Ikeda, Keisuke Kakimoto, Miyako Watanabe, Naoya Shindo, Akito Tsuruta, Hisako Ikeyama, Kengo Hamamura, Kazuhiro Higashi, Tomohiro Yamashita, Hideaki Kondo, Yuya Yoshida, Masaki Matsuda, Takashi Ogino, Kazutaka Tokushige, Kazufumi Itcho, Yoko Furuichi, Takaharu Nakao, Kaori Yasuda, Atsushi Doi, Toshiaki Amamoto, Hironori Aramaki, Makoto Tsuda, Kazuhide Inoue, Akio Ojida, Satoru Koyanagi, Shigehiro Ohdo

EBioMedicine 13 262 - 273 2016.6

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.ebiom.2016.10.008
Design of Coordination Interaction of Zn(II) Complex with Oligo-Aspartate Peptide to Afford a High-Affinity Tag-Probe Pair Reviewed International journal

Hirokazu Fuchida, Shigekazu Tabata, Naoya Shindo, Ippei Takashima, Qiao Leng, Yuji Hatsuyama, Itaru Hamachi, Akio Ojida

Bulletin of the Chemical Society of Japan 88 784 - 791 2015.3

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1246/bcsj.20150037
Design of a binuclear Ni(II)-iminodiacetic acid (IDA) complex for selective recognition and covalent labeling of His-tag fused proteins Reviewed International journal

Ikuko Takahira, Hirakazu Fuchida, Shigekazu Tabata, Naoya Shindo, Shohei Uchinomiya, Itaru Hamachi, Akio Ojida

Bioorganic & Medicinal Chemistry Letters 24 2855 - 2858 2014.3

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.bmcl.2014.04.096
Selective Synthesis of Polysubstituted Dihydroquinolines and α,β-Unsaturated Amidines by a Catalytic Reaction of Ynamides with Ketimines Reviewed International journal

45 2328 - 2336 2013.5

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1055/s-0033-1339191

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Books

生体分子環境の化学

進藤直哉, 王子田彰夫（ Role： Joint author）

化学同人 2023.2

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Language：Japanese Book type：Scholarly book
Handbook of In Vivo Chemistry in Mice: From Lab to Living System

Naoya Shindo, Akio Ojida（ Role： Joint author）

Wiley-VHC 2020.1

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Language：English Book type：Scholarly book

Presentations

標的タンパク質を狙い撃ちするコバレントドラッグの有機化学 Invited

進藤直哉

徳島大学研究クラスター「独自の解析技術と疾患科学の融合によるリボソーム創薬の創生」第3回セミナー 2023.2

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Event date： 2023.2

Language：Japanese Presentation type：Oral presentation (general)

Venue：徳島大学 (徳島市) Country：Japan
コバレントドラッグ創薬を志向したシステインの可逆的共有結合修飾化学 Invited

進藤直哉

第3回モダリティ創薬デザイン研究会シンポジウム 2022.2

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Event date： 2022.2

Language：Japanese Presentation type：Oral presentation (general)

Venue：オンライン Country：Japan
コバレントドラッグを志向したシステイン反応性求電子基の探索 Invited

進藤直哉

第2回生体適合化学の進歩インタラクティブフォーラム 2021.3

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Event date： 2021.3

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
Selective and reversible modification of kinase cysteines with chlorofluoroacetamides Invited

2019.10

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Event date： 2019.10

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
狙ったタンパク質と選択的に共有結合を作るコバレントドラッグの有機化学 Invited

進藤直哉

第6回BRIGHTシンポジウム 2019.7

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Event date： 2019.7

Language：Japanese Presentation type：Oral presentation (general)

Venue：徳島 Country：Japan
コバレント阻害剤の標的選択性向上を指向した新規反応基の探索とキナーゼ阻害剤への応用 Invited

進藤直哉

日本薬学会第139年会 2019.3

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Event date： 2019.3

Language：Japanese Presentation type：Symposium, workshop panel (public)

Venue：千葉 Country：Japan
Selective and Reversible Covalent Modification of Non-Catalytic Cysteines with Weakly Reactive α-Chlorofluoroacetamides Invited International conference

2018.3

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Event date： 2018.6

Language：English Presentation type：Oral presentation (general)

Country：Japan
コバレント阻害剤の標的特異性向上を目指した新規反応基の探索とEGFR阻害剤への応用 Invited

進藤直哉、渕田大和、初山勇次、渡　公佑、小野真弓、王子田彰夫

第35回メディシナルケミストリーシンポジウム 2017.10

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Event date： 2018.6

Language：Japanese Presentation type：Oral presentation (general)

Venue：名古屋大学（名古屋） Country：Japan
システインの可逆的共有結合修飾を指向したジハロアセタミド化学の拡張

進藤直哉, #山根太輝, #鉄川涼, 善明直輝, 田畑香織, 吉田優哉, 松永直哉, 王子田彰夫

日本薬学会第144年会 2024.3

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Event date： 2024.3

Language：Japanese

Venue：横浜市 Country：Japan
コバレントドラッグを指向した細胞内反応化学の探索 Invited

進藤直哉

第24回スクリプス・バイオメディカルフォーラム 2023.12

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Event date： 2023.12

Language：Japanese Presentation type：Oral presentation (general)

Venue：大阪市 Country：Japan
コバレントドラッグを指向したリジン選択的反応化学の開発

進藤直哉, #田中雄大, #谷川敦哉, 善明直輝, #鉄川涼, #林シン城, @喜多俊介, @前仲勝実, 王子田彰夫

第40回メディシナルケミストリーシンポジウム 2023.11

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Event date： 2023.11

Language：Japanese Presentation type：Oral presentation (general)

Venue：名古屋市 Country：Japan
タンパク質の共有結合阻害を指向した細胞内反応化学 Invited

進藤直哉

第96回日本生化学会大会 2023.10

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Event date： 2023.10

Language：Japanese Presentation type：Oral presentation (general)

Venue：福岡市 Country：Japan
不可逆阻害剤への応用を目指したひずみ解消型反応基の開発

#徳永啓佑、進藤直哉、#佐藤磨美、@桑田啓子、王子田彰夫

ケミカルバイオロジー学会第14回年会 2019.6

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Event date： 2021.6

Language：Japanese

Venue：名古屋 Country：Japan
ひずみ解消型反応基の開拓と不可逆阻害剤開発への応用

#徳永啓佑、進藤直哉、#佐藤磨美、@桑田啓子、王子田彰夫

第14回バイオ関連化学シンポジウム 2020.9

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Event date： 2020.9

Language：Japanese

Venue：オンライン Country：Japan
Bicyclobutane carboxylic amides as a strain-release type electrophile for selective targeting of proteins in live cells

Naoya Shindo, #Keisuke Tokunaga, #Mami Sato, @Keiko Kuwata, Akio Ojida

2020.3

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Event date： 2020.3

Language：English

Country：Japan
ひずみ解消型反応基の開拓と不可逆阻害剤開発への応用

徳永啓佑、進藤直哉、佐藤磨美、桑田啓子、王子田彰夫

日本薬学会第140年会 2020.3

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Event date： 2020.3

Language：Japanese

Country：Japan
ビシクロブタンのひずみ解消反応を利用したタンパク質の標的選択的不可逆阻害

進藤直哉、#徳永啓佑、#佐藤磨美、@桑田啓子、#渕田大和、王子田彰夫

第37回メディシナルケミストリーシンポジウム 2019.11

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Event date： 2019.11

Language：Japanese

Venue：八王子 Country：Japan
ひずみ解消型反応のタンパク質不可逆阻害への応用

#徳永啓佑、進藤直哉、#佐藤磨美、@桑田啓子、王子田彰夫

第13回バイオ関連化学シンポジウム 2019.9

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Event date： 2019.9

Language：Japanese Presentation type：Oral presentation (general)

Venue：仙台 Country：Japan
Selective and reversible modification of kinase cysteines with chlorofluoroacetamides International conference

Naoya Shindo, #Hirokazu Fuchida, #Mami Sato, Kosuke Watari, @Keiko Kuwata, Mayumi Ono, Akio Ojida

VIII EFMC International Symposium on Advances in Synthetic and Medicinal Chemistry 2019.9

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Event date： 2019.9

Language：English

Country：Greece
クロロフルオロアセタミドを利用した不可逆的キナーゼ阻害剤の開発

進藤直哉、#渕田大和、#佐藤磨美、渡公佑、@桑田啓子、小野眞弓、王子田彰夫

日本ケミカルバイオロジー学会 2019.6

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Event date： 2019.6

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
標的選択的コバレント阻害剤への応用を志向したひずみ解消型反応基の開発

進藤直哉、#徳永啓佑、#佐藤磨美、#渕田大和、王子田彰夫

第44回反応と合成の進歩シンポジウム 2018.11

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Event date： 2018.11

Language：Japanese Presentation type：Oral presentation (general)

Venue：熊本 Country：Japan
コバレントドラッグへの応用を目指したひずみ解消型反応基の開発

#徳永啓佑、進藤直哉、王子田彰夫

創薬懇話会in志賀島 2018.6

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Event date： 2018.6 - 2019.6

Language：Japanese

Venue：福岡 Country：Japan
CFA基の反応特性を利用したキナーゼ阻害剤の開発

#佐藤磨美、進藤直哉、#渕田大和、#三浦千鶴、#岡本恵、#初山勇次、小野眞弓、渡公佑、王子田彰夫

創薬懇話会in志賀島 2018.6

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Event date： 2018.6

Language：Japanese

Venue：福岡 Country：Japan
CFA基を利用したコバレントドラッグ創薬

進藤直哉, 渕田大和, 佐藤磨美, 大澤智代, 徳永啓佑, 小野眞弓, 渡　公佑, 王子田彰夫

日本薬学会第138年会 2018.3

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Event date： 2018.6

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
コバレント阻害剤の標的特異性向上を目指した新規反応性基の探索とEGFR阻害剤への応用

進藤直哉、渕田大和、初山勇次、渡　公佑、小野真弓、王子田彰夫

日本薬学会第137年会 2017.3

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Event date： 2018.6

Language：Japanese Presentation type：Oral presentation (general)

Venue：東北大学（仙台） Country：Japan
CFAケミストリーによる高選択的不可逆阻害剤の開発

渕田大和、進藤直哉、佐藤磨美、初山勇次、三浦千鶴、岡本　恵、渡　公佑、小野真弓、王子田彰夫

日本化学会第97春季年会 2017.3

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Event date： 2018.6

Language：Japanese

Venue：東京 Country：Japan
CFAケミストリーによるタンパク質の不可逆阻害

進藤直哉、渕田大和、佐藤磨美、渡　公佑、小野真弓、王子田彰夫

日本ケミカルバイオロジー学会第12回年会 2017.6

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Event date： 2018.6

Language：Japanese Presentation type：Oral presentation (general)

Venue：北海道大学（札幌） Country：Japan
CFAケミストリーを利用した標的タンパク質特異的な不可逆阻害

渕田大和、進藤直哉、佐藤磨美、初山勇次、三浦千鶴、岡本　恵、渡　公佑、小野真弓、王子田彰夫

第11回バイオ関連化学シンポジウム 2017.9

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Event date： 2018.6

Language：Japanese Presentation type：Oral presentation (general)

Venue：東京大学(東京) Country：Japan
コバレントドラッグの化学(1) : CFA基の反応特性を利用したキナーゼ阻害剤の開発

佐藤磨美, 進藤直哉, 渕田大和, 初山勇次, 三浦千鶴, 岡本　恵, 渡　公佑, 小野眞弓, 王子田彰夫

日本化学会第98春季年会 2018.3

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Event date： 2018.6

Language：Japanese Presentation type：Oral presentation (general)

Venue：日本大学（船橋） Country：Japan
コバレントドラッグの化学(2) : ひずみ解消型反応基の開拓と阻害剤開発への応用

徳永啓佑, 進藤直哉, 王子田彰夫

日本化学会第98春季年会 2018.3

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Event date： 2018.6

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan

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MISC

コバレントドラッグ　共有結合でundruggableな標的も狙える低分子医薬　がんや感染症分野で上市が続く注目のモダリティ

進藤直哉, 王子田彰夫

実験医学 42 ( 11 ) 1720 - 1730 2024.7 （ ISSN:0288-5514 ）

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Language：Japanese Publisher：(株)羊土社

コバレントドラッグ(共有結合性医薬)は,標的タンパク質と共有結合を形成する低分子医薬である.標的と強く持続的に結合するため,従来の可逆的な薬剤と比べ,薬効の増強や作用時間の延長といった利点が期待できる.かつては安全性の懸念から開発が避けられる傾向にあったが,近年では利点が見直され,標的選択的に共有結合するよう合理的にデザインされたコバレントドラッグの創薬研究が隆盛となっている.本稿では,低分子創薬において最近存在感を増すコバレントドラッグについて,研究開発の歴史と現状,今後の展望について紹介したい.(著者抄録)
コバレントドラッグのための細胞内反応化学 Reviewed

進藤直哉, 王子田彰夫

有機合成化学協会誌 2024.1

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Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)

DOI： https://doi.org/10.5059/yukigoseikyokaishi.82.50
コバレントドラッグに使える新たな有機化学を目指して Reviewed

進藤直哉

ファルマシア 2021.3

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Language：Japanese

DOI： 10.14894/faruawpsj.57.3_224_1
In vivo targeting endogenous proteins with reactive small molecules

Naoya Shindo, Akio Ojida

Wiley-VCH 2019.12

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Language：English Publishing type：Article, review, commentary, editorial, etc. (scientific journal)

DOI： doi.org/10.1002/9783527344406.ch10
コバレントドラッグ創薬のための創薬有機化学 Reviewed

進藤直哉、王子田彰夫

ファルマシア 2019.10

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Language：Japanese

DOI： 10.14894/faruawpsj.55.10_939
SYNTHESIS OF AZAHETEROCYCLES AND RELATED MOLECULES BY Tf₂NH-CATALYZED CYCLOADDITIONS

Naoya Shindo, Kiyosei Takasu

HETEROCYCLES 2018.1

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Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)

DOI： 10.3987/REV-17-875

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Industrial property rights

Patent	Number of applications: 2	Number of registrations: 2
Utility model	Number of applications: 0	Number of registrations: 0
Design	Number of applications: 0	Number of registrations: 0
Trademark	Number of applications: 0	Number of registrations: 0

Professional Memberships

日本ケミカルバイオロジー学会
有機合成化学協会
日本薬学会
日本薬学会　医薬化学部会
日本化学会

Academic Activities

Screening of academic papers

Role(s)： Peer review

2023

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Type：Peer review

Number of peer-reviewed articles in foreign language journals：2
総務担当委員

日本ケミカルバイオロジー学会第15回年会（オンライン） 2021.6

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Type：Competition, symposium, etc.
実行委員

第14回バイオ関連化学シンポジウム（オンライン） 2020.9

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Type：Competition, symposium, etc.
Screening of academic papers

Role(s)： Peer review

2020

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Type：Peer review

Number of peer-reviewed articles in foreign language journals：2

Research Projects

Development of organic chemistry targeting biomolecules in live animals

Grant number：23H05405 2023 - 2028

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Specially Promoted Research

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Authorship：Coinvestigator(s) Grant type：Scientific research funding

CiNii Research
新規可逆的リジン修飾化学の開発とコバレントドラッグ創薬の標的拡張

Grant number：22H02222 2022 - 2024

日本学術振興会科学研究費助成事業基盤研究(B)

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Authorship：Principal investigator Grant type：Scientific research funding
住友財団・基礎科学研究助成/独自の反応基を利用した新規SARS-CoV-2メインプロテアーゼ阻害剤の開発

2021

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Grant type：Donation
次世代のコバレントドラッグ創薬を志向した反応基の開発とプロテオミクス研究

Grant number：19H02854 2019 - 2021

日本学術振興会科学研究費助成事業基盤研究(B)

進藤直哉

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Authorship：Principal investigator Grant type：Scientific research funding

コバレントドラッグが標的タンパク質と不可逆的に結合する利点を安全に活かすには、高い標的選択性の実現が不可欠である。申請者は有機化学的観点から、標的選択性を高めるための新たな反応基を探索してきた。本研究ではシステイン残基に対する新たな反応基として、従来のマイケルアクセプターやα-ハロアセタミドとは構造が大きく異なる、ビシクロブタンを検討する。また、可逆的なリガンドだけでなく反応基自身もタンパク質選択性に影響するという独自の視点のもと、リガンドと反応基の組み合わせによる選択性変化を定量的に解析するプロテオミクス研究を展開し、次世代のコバレント阻害剤開発に資する有益な知見を提供する。

CiNii Research
独自の反応基を利用した高選択的コバレントドラッグ開発プラットフォーム

2019 - 2021

AMED

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Authorship：Principal investigator Grant type：Contract research
高度な標的特異性を志向した新規コバレント阻害剤の創製

Grant number：17K15483 2017 - 2018

科学研究費助成事業若手研究(B)

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Authorship：Principal investigator Grant type：Scientific research funding

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Class subject

物理化学的測定法

2024.4 - 2024.9 First semester
創薬科学総論III

2023.12 - 2024.2 Winter quarter
薬学基礎実習II

2023.10 - 2024.3 Second semester
薬学基礎実習II

2022.10 - 2023.3 Second semester
基礎科学実習

2021.12 - 2022.2 Winter quarter
薬学基礎実習II

2021.4 - 2021.9 First semester
薬学基礎実習II

2020.4 - 2020.9 First semester
薬学基礎実習II

2019.4 - 2019.9 First semester
薬学基礎実習II

2018.4 - 2018.9 First semester

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FD Participation

2023.11 Role：Participation Title：第２回薬学部局FD講演会「機関間連携」

Organizer：[Undergraduate school/graduate school/graduate faculty]

Media Coverage

「全株対応コロナ治療薬に光」新型コロナウイルス感染症治療薬開発に関する記事が2022年11月8日付の西日本新聞一面に掲載 Newspaper, magazine

西日本新聞 2022.11

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「全株対応コロナ治療薬に光」新型コロナウイルス感染症治療薬開発に関する記事が2022年11月8日付の西日本新聞一面に掲載