論文 - 詳細
| RRC ID | 55965 |
|---|---|
| 著者 | Kimura Y, Negishi H, Matsuda A, Endo N, Hangai S, Inoue A, Nishio J, Taniguchi T, Yanai H. |
| タイトル | Novel chemical compound SINCRO with dual function in STING-type I interferon and tumor cell death pathways. |
| ジャーナル | Cancer Sci |
| Abstract |
Recent years have seen a number of regulatory approvals for immune oncology or immunotherapies based on their ability to enhance antitumor immune responses. Nevertheless, the majority of patients remain refractory to these treatments; hence, new therapies that augment current immunotherapies are required. Innate immune receptors that recognize nucleic acids are potent activators of subsequent T-cell responses and, as a result, can evoke potent antitumor immune responses. Herein, we present a novel compound N-{3-[(1,4'-bipiperidin)-1'-yl]propyl}-6-[4-(4-methylpiperazin-1-yl)phenyl]picolinamide (SINCRO; STING-mediated interferon-inducing and cytotoxic reagent, original) as an anticancer drug that activates the cytosolic DNA-sensing STING (stimulator of interferon genes) signaling pathway leading to the induction of type I interferon (IFN) genes. Indeed, IFN-β gene induction by SINCRO is abolished in STING-deficient cells. In addition to its IFN-inducing activity, SINCRO shows STING-independent cytotoxic activity against cancer cells. SINCRO does not evoke DNA double-strand break or caspase-3 cleavage. Thus, SINCRO induces cell death in a method different from conventional apoptosis-inducing pathways. Finally, we provide evidence that giving SINCRO significantly attenuates in vivo tumor growth by both type I IFN-dependent and independent mechanisms. Thus, SINCRO is an attractive anticancer compound with dual function in that it evokes type I IFN response to promote antitumor immunity as well as inducing tumor cell death. SINCRO may provide a new platform for the development of drugs for effective cancer therapy. |
| 巻・号 | 109(9) |
| ページ | 2687-2696 |
| 公開日 | 2018-9-1 |
| DOI | 10.1111/cas.13726 |
| PMID | 29981256 |
| PMC | PMC6125434 |
| MeSH | 3T3 Cells Amides / chemistry Amides / pharmacology* Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Cell Line, Tumor Cell Proliferation / drug effects DNA Breaks, Double-Stranded / drug effects HEK293 Cells HeLa Cells Humans Immunity, Innate / drug effects* Interferon-beta / biosynthesis* Interferon-beta / genetics Interferon-beta / metabolism Membrane Proteins / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Neoplasms / drug therapy* Neoplasms / immunology* Neoplasms / pathology Picolinic Acids / chemistry Picolinic Acids / pharmacology* Piperidines / chemistry Piperidines / pharmacology* Signal Transduction / drug effects |
| IF | 4.751 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | EL4(RCB1641) |