Novel mouse model for evaluating in vivo efficacy of xCT inhibitor
xCT, a well-known cystine transporter, is reported to be involved in the proliferation of various cells, such as cancer cells, immune cells, and fibroblasts. xCT inhibitor is expected to be a promising drug for cancer or immune diseases. However, there are little studies reporting that xCT inhibitor...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319356889 |
| _version_ | 1819266026750083072 |
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| author | Ryosuke Yoshioka Yusuke Fujieda Yamato Suzuki Osamu Kanno Asako Nagahira Tomohiro Honda Masao Murakawa Hiroshi Yukiura |
| author_facet | Ryosuke Yoshioka Yusuke Fujieda Yamato Suzuki Osamu Kanno Asako Nagahira Tomohiro Honda Masao Murakawa Hiroshi Yukiura |
| author_sort | Ryosuke Yoshioka |
| collection | DOAJ |
| description | xCT, a well-known cystine transporter, is reported to be involved in the proliferation of various cells, such as cancer cells, immune cells, and fibroblasts. xCT inhibitor is expected to be a promising drug for cancer or immune diseases. However, there are little studies reporting that xCT inhibitors improve disease progression in vivo. To invent potent xCT inhibitors in vivo, we established a new in vivo model for assessing efficacy of xCT inhibition.dl-propargylglycine (PPG) was administered intraperitoneally to wild-type C57BL/6J mice. Concentration of cystathionine, another substrate of xCT, in the thymus and spleen was measured by LC-MS/MS.PPG increased cystathionine amounts in the thymus and spleen in a dose- and time-dependent manner. At 7 h after PPG administration, the efficacy of erastin, a representative xCT inhibitor, was clearly shown. We synthesized a new compound, Compound A, which had much higher inhibitory effect on xCT than erastin both in vitro and in vivo.We established a mouse model of PPG-induced cystathionine accumulation for assessing xCT inhibition in vivo. By using this model, we discovered that Compound A was approximately 15 times more effective in vivo than erastin. Keywords: xCT, SLC7A11, System xc−, Cystathionine, Erastin |
| first_indexed | 2024-12-23T20:54:44Z |
| format | Article |
| id | doaj.art-1c4bfe3a829b4db59cfd8b07886e1ee0 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-23T20:54:44Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-1c4bfe3a829b4db59cfd8b07886e1ee02022-12-21T17:31:33ZengElsevierJournal of Pharmacological Sciences1347-86132019-07-011403242247Novel mouse model for evaluating in vivo efficacy of xCT inhibitorRyosuke Yoshioka0Yusuke Fujieda1Yamato Suzuki2Osamu Kanno3Asako Nagahira4Tomohiro Honda5Masao Murakawa6Hiroshi Yukiura7Corresponding author. Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan. Fax: +81 3 5740 3641.; Asubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanAsubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanAsubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanAsubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanAsubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanAsubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanAsubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanAsubio Pharma Co., Ltd., 6-4-3, Minatojima-minamimachi, Chuou-ku, Kobe, JapanxCT, a well-known cystine transporter, is reported to be involved in the proliferation of various cells, such as cancer cells, immune cells, and fibroblasts. xCT inhibitor is expected to be a promising drug for cancer or immune diseases. However, there are little studies reporting that xCT inhibitors improve disease progression in vivo. To invent potent xCT inhibitors in vivo, we established a new in vivo model for assessing efficacy of xCT inhibition.dl-propargylglycine (PPG) was administered intraperitoneally to wild-type C57BL/6J mice. Concentration of cystathionine, another substrate of xCT, in the thymus and spleen was measured by LC-MS/MS.PPG increased cystathionine amounts in the thymus and spleen in a dose- and time-dependent manner. At 7 h after PPG administration, the efficacy of erastin, a representative xCT inhibitor, was clearly shown. We synthesized a new compound, Compound A, which had much higher inhibitory effect on xCT than erastin both in vitro and in vivo.We established a mouse model of PPG-induced cystathionine accumulation for assessing xCT inhibition in vivo. By using this model, we discovered that Compound A was approximately 15 times more effective in vivo than erastin. Keywords: xCT, SLC7A11, System xc−, Cystathionine, Erastinhttp://www.sciencedirect.com/science/article/pii/S1347861319356889 |
| spellingShingle | Ryosuke Yoshioka Yusuke Fujieda Yamato Suzuki Osamu Kanno Asako Nagahira Tomohiro Honda Masao Murakawa Hiroshi Yukiura Novel mouse model for evaluating in vivo efficacy of xCT inhibitor Journal of Pharmacological Sciences |
| title | Novel mouse model for evaluating in vivo efficacy of xCT inhibitor |
| title_full | Novel mouse model for evaluating in vivo efficacy of xCT inhibitor |
| title_fullStr | Novel mouse model for evaluating in vivo efficacy of xCT inhibitor |
| title_full_unstemmed | Novel mouse model for evaluating in vivo efficacy of xCT inhibitor |
| title_short | Novel mouse model for evaluating in vivo efficacy of xCT inhibitor |
| title_sort | novel mouse model for evaluating in vivo efficacy of xct inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319356889 |
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