Identification of small molecular compounds with PD-1 / PD-L1 inhibitory activity by in silico
Project/Area Number |
18K07315
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Shizuoka Cancer Center Research Institute |
Principal Investigator |
Ashizawa Tadashi 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (10443441)
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Co-Investigator(Kenkyū-buntansha) |
石川 吉伸 静岡県立大学, 薬学部, 准教授 (00305004)
安藤 隆幸 静岡県環境衛生科学研究所, 医薬食品部, 主査 (40402226)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | PD-L1 / PD-1/PD-L1 / PD-1/PD-L1 inhibitor / PD-1/PD-L inhibitor / 免疫チェックポイント |
Outline of Final Research Achievements |
Antibody drugs such as the immune checkpoint molecule-inhibiting antibody nivolumab have been reported to have therapeutic effects on renal cancer, bladder cancer and malignant lymphoma in addition to the life-prolonging effect on melanoma and non-small cell lung cancer. On the other hand, antibody drugs are expensive, and side effects such as adverse immune events have been reported, and there is an urgent need to develop new target molecular drugs such as low molecular weight compounds that can be expected to have the same effects as immune checkpoint antibodies. We are from the compound library of Shizuoka Prefectural Institute of Environmental Health Sciences. We found one small molecule oral PD-1 / PD-L1 binding inhibitor and filed a patent application. In the future, we plan to carry out drug efficacy evaluations, pharmacokinetic studies and nonclinical safety studies of the developed compounds.
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Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント分子PD-1/PD-L1阻害抗体に代わる低分子化合物の開発は、1つの社会問題であり臨床現場で求められている研究課題でもある。さらに今後は高齢者のがん患者数が急増することを考慮すると免疫チェックポイント阻害抗体と同様の効果を期待できる経口低分子化合物などの新しい標的分子薬の開発が急務である。我々のように創薬プラットフォームを持ち、かつ免疫治療の研究施設(橋渡し研究)を持つアカデミアはほとんどなく、独自性において有意な立場にあるものと考えられる。また、企業とのマッチングの可能性を打診したい。
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Mutational concordance analysis provides supportive information for double cancer Diagnosis.2021
Author(s)
Hatakeyama, K, Nagashima T, Notsu, A, Ohshima K, Ohnami S, Ohnami, S, Shimoda Y, Naruoka A, Maruyama K, Iizuka A, Ashizawa T, Kenmotsu T, Mochizuki T, Urakami K, Akiyama Y and Yamaguchi K.
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Journal Title
BMC Cancer
Volume: 21
Issue: 1
Pages: 181-181
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of preoperative chemoradiotherapy on the immunological status of rectal cancer patients.2020
Author(s)
Yasui K, Kondou R, Iizuka A, Miyata H, Tanaka E, Ashizawa T, Nagashima T, Ohshima K, Urakami K, Kusuhara M, Muramatsu K, Sugino T, Yamguchi K, Mori K, Harada H, Nishimura T, Kagawa H, Yamakawa Y, Hino H, Shiomi A, Akiyama Y.
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Journal Title
J Radiat Res.
Volume: 61
Issue: 5
Pages: 766-775
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Increase in toxicity of anticancer drugs by PMTPV, a claudin-1-binding peptide, mediated via down-regulation of claudin-1 in human lung adenocarcinoma A549 cells2020
Author(s)
Nasako, H., Takashina, Y., Eguchi, H., Ito, A., Ishikawa, Y., Matsunaga, T., Endo, S., Ikari, A
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Journal Title
International Journal of Molecular Sciences
Volume: 21
Issue: 16
Pages: 5909-5909
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Claudin-2 binding peptides, VPDSM and DSMKF, down-regulate claudin-2 expression and anticancer resistance in human lung adenocarcinoma A549 cells.2020
Author(s)
Nasako H, Akizuki R, Takashina Y, Ishikawa Y, Shinoda T, Shirouzu M, Asai T, Matsunaga T, Endo S, Ikari A.
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Journal Title
Biochim Biophys Acta Mol Cell Res.
Volume: 1867
Issue: 4
Pages: 118642-118642
DOI
Related Report
Peer Reviewed
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[Journal Article] Antitumor activity of the PD-1/PD-L1 binding inhibitor BMS-202 in the humanized MHC-double knockout NOG mouse2019
Author(s)
Ashizawa T, Iizuka A, Tanaka E, Kondou R, Miyata H, Maeda C, Sugino T, Yamaguchi K, Ando T, Ishikawa Y, Ito M, Akiyama Y.
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Journal Title
Biomedical Research
Volume: 40
Issue: 6
Pages: 243-250
DOI
NAID
ISSN
0388-6107, 1880-313X
Year and Date
2019-12-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status.2019
Author(s)
Ashizawa T, Iizuka A, Maeda C, Tanaka E, Kondou R, Miyata H, Sugino T, Kawata T, Deguchi S, Mitsuya K, Hayashi N, Asai A, Ito M, Yamaguchi K, Akiyama Y.
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Journal Title
Immunol Lett.
Volume: 216
Pages: 43-50
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Concise Synthesis of TAN1251C2019
Author(s)
Nagasaka Y, Asakawa T, Shintaku S, Masuda A, Matsumura K, Inai M, Ishikawa Y, Egi M, Hamashima Y, Kan T.
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Journal Title
HETEROCYCLES
Volume: 99
Issue: 2
Pages: 1095-1116
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of a neoantigen epitope in a melanoma patient with good response to anti-PD-1 antibody therapy2019
Author(s)
Nonomura C, Otsuka M, Kondou R, Iizuka A, Miyata H, Ashizawa T, Sakura N, Yoshikawa S, Kiyohara Y, Ohshima K, Urakami K, Nagashima T, Ohnami S, Kusuhara M, Mitsuya K, Hayashi N, Nakasu Y, Mochizuki T, Yamaguchi K, Akiyama Y
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Journal Title
Immunol Lett
Volume: 208
Pages: 52-59
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Classification of tumor microenvironment immune types based on immune response-associated gene expression2019
Author(s)
Kondou R, Iizuka A, Nonomura C, Miyata H, Ashizawa T, Nagashima T, Ohshima K, Urakami K, Kusuhara M, Yamaguchi K, Akiyama Y
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Journal Title
Int J Oncol
Volume: 54
Pages: 219-228
DOI
Related Report
Peer Reviewed / Open Access
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