Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama City, 223-8522, Japan.
J Antibiot (Tokyo). 2019 Dec;72(12):899-905. doi: 10.1038/s41429-019-0219-3. Epub 2019 Aug 9.
Endoplasmic reticulum (ER) stress and the subsequent adaptive cellular response, termed the unfolded protein response (UPR), have been implicated in several diseases, including cancer. In this review, I present a brief introduction to ER stress and the UPR and then summarize the importance of the IRE1α-XBP1 branch as a target for anticancer drug discovery. In addition, I introduce our approach to the identification of inhibitors against the IRE1α-XBP1 branch from microbial cultures. As a result of our screening, toyocamycin has been identified and toyocamycin showed anticancer activity against multiple myeloma.
内质网（ER）应激及其随后的适应性细胞反应，称为未折叠蛋白反应（UPR），与多种疾病有关，包括癌症。在这篇综述中，我简要介绍了 ER 应激和 UPR，然后总结了 IRE1α-XBP1 分支作为抗癌药物发现的靶点的重要性。此外，我还介绍了我们从微生物培养物中鉴定针对 IRE1α-XBP1 分支抑制剂的方法。作为我们筛选的结果，已鉴定出托泊霉素，并且托泊霉素对多发性骨髓瘤具有抗癌活性。
