2018年饶燏课题组与生科院刘万里课题组合作在《Cell Research》期刊首先报道了通过构建新型BTK蛋白高效降解剂，克服了临床上B细胞恶性肿瘤由于BTK蛋白突变引起的对临床一线药物ibrutinib的耐药性，新策略的靶向选择性远优于ibrutinib，能够避免ibrutinib产生的严重副作用。随后，饶燏课题组与北京大学肿瘤医院朱军课题组，以及刘万里课题组合作在血液学国际著名期刊《白血病》（Leukemia）在线发表了最新研究成果《利用PROTAC技术降解多种突变型BTK蛋白克服ibrutinib耐药的非霍奇金淋巴瘤的潜在治疗方案》（Degradation of Bruton’s tyrosine kinase mutants by PROTACs forpotential treatment of ibrutinib-resistant Non-Hodgkin lymphomas）。通过构建新型高溶解度的BTK蛋白高效降解剂，成功高效的降解多种临床相关的突变型BTK蛋白，克服了临床上非霍奇金淋巴瘤由于BTK蛋白突变引起的对临床一线药物ibrutinib的耐药性。更为重要的是，新策略克服肿瘤耐药的有效性得到了体内实验的验证。
1）新合成的PROTAC小分子既能够选择性地结合到BTK蛋白，又能够选择性地结合到E3泛素化连接酶，并且还能够拉近两蛋白在空间上的距离，起到泛素化降解BTK的目的；
目录概述：
目前，该著作可在线免费下载前言、目录和第一章(Chapter 1:PROTAC-mediated Target Degradation: A ParadigmChanger in Drug Discovery)，整本下载需179美元。
参考文献：
[1] Sakamoto, KM., et al., Protacs:chimeric molecules that target proteins to the Skp1-Cullin-F box complex forubiquitination and degradation. PNAS, 2001. 98: p. 8554-8559.
[2] Sun, Y., et al., PROTAC-inducedBTK degradation as a novel therapy for mutated BTK C481S inducedibrutinib-resistant B-cell malignancies. Cell Research, 2018. 28: p. 779–781.
[3] Buhimschi, A.D., et al.,Targeting the C481S Ibrutinib-Resistance Mutation in Bruton's Tyrosine KinaseUsing PROTAC-Mediated Degradation. Biochemistry, 2018. 57(26): p. 3564-3575.
[4] Zorba, A., et al., Delineatingthe role of cooperativity in the design of potent PROTACs for BTK. Proceedingsof the National Academy of Sciences, 2018. 115(31): p. E7285-E7292.
[5 Dobrovolsky, D., et al., Brutontyrosine kinase degradation as a therapeutic strategy for cancer. Blood, 2019.133(9): p. 952-961.
[6] Sun, Y., et al., Degradation ofBruton's tyrosine kinase mutants by PROTACs for potential treatment ofibrutinib-resistant non-Hodgkin lymphomas. Leukemia, 2019. 33(8): p. 2105-2110.
[7] Tinworth, C.P., et al.,PROTAC-Mediated Degradation of Bruton's Tyrosine Kinase Is Inhibited byCovalent Binding. ACS Chemical Biology, 2019. 14(3): p. 342-347.
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