{"title":"ALK 抑制剂 AMX6001 在无性大细胞淋巴瘤 Karpas299 小鼠模型中的发现和疗效研究","authors":"Debasis Das, Lingzhi Xie, Dandan Qiao, Yuxi Cao, Jianhe Jia, Yong Li, Jian Hong","doi":"10.1016/j.ejmcr.2024.100209","DOIUrl":null,"url":null,"abstract":"<div><p>Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of anaplastic large cell lymphoma (ALCL). We identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound <strong>9</strong> (<strong>AMX6001</strong>) showed better <em>in vitro</em> activity against ALK and NPM-ALK kinase and significantly inhibited proliferation of Karpas299 and SU-DHL-1 cell lines. <em>In vivo</em> efficacy of compound <strong>9</strong> was better than reference standard ceritinib in ALCL Karpas299 mice models. Daily oral treatment of compound <strong>9</strong> (25 mg/kg) induced tumor suppression TGI up to 95.8 % in ALCL models.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100209"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000815/pdfft?md5=a3a86c8978cc4e8877ca8b225053a789&pid=1-s2.0-S2772417424000815-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Discovery and efficacy study of an ALK inhibitor AMX6001 in anaplastic large cell lymphoma Karpas299 mice models\",\"authors\":\"Debasis Das, Lingzhi Xie, Dandan Qiao, Yuxi Cao, Jianhe Jia, Yong Li, Jian Hong\",\"doi\":\"10.1016/j.ejmcr.2024.100209\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of anaplastic large cell lymphoma (ALCL). We identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound <strong>9</strong> (<strong>AMX6001</strong>) showed better <em>in vitro</em> activity against ALK and NPM-ALK kinase and significantly inhibited proliferation of Karpas299 and SU-DHL-1 cell lines. <em>In vivo</em> efficacy of compound <strong>9</strong> was better than reference standard ceritinib in ALCL Karpas299 mice models. Daily oral treatment of compound <strong>9</strong> (25 mg/kg) induced tumor suppression TGI up to 95.8 % in ALCL models.</p></div>\",\"PeriodicalId\":12015,\"journal\":{\"name\":\"European Journal of Medicinal Chemistry Reports\",\"volume\":\"12 \",\"pages\":\"Article 100209\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2772417424000815/pdfft?md5=a3a86c8978cc4e8877ca8b225053a789&pid=1-s2.0-S2772417424000815-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Medicinal Chemistry Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2772417424000815\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772417424000815","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Discovery and efficacy study of an ALK inhibitor AMX6001 in anaplastic large cell lymphoma Karpas299 mice models
Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of anaplastic large cell lymphoma (ALCL). We identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 9 (AMX6001) showed better in vitro activity against ALK and NPM-ALK kinase and significantly inhibited proliferation of Karpas299 and SU-DHL-1 cell lines. In vivo efficacy of compound 9 was better than reference standard ceritinib in ALCL Karpas299 mice models. Daily oral treatment of compound 9 (25 mg/kg) induced tumor suppression TGI up to 95.8 % in ALCL models.
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