Discovery of BTK Kinase Inhibitors as Targeted Therapeutics for B-cell Malignancies

B细胞恶性肿瘤（Bcellmalignancies）起源于B淋巴细胞在其生长发育的关键时期内不受控制的生长。酪氨酸激酶BTK(Bruton'styrosinekinase)是非受体酪氨酸激酶Tec家族的成员，其激活对于多种B细胞恶性肿瘤的生长和存活都至关重要。本论文采用了“以化合物为中心”的高并行筛药策略，并基于Ba/F3细胞毒性差异高通量分析筛选了实验室内部化合物库，并获得BTK靶标激酶的“Hit”化合物。之后，将“Hit”化合物进行一系列的结构优化，最终筛选得到有效的选择性的BTK激酶小分子抑制剂XMU-MP-3。XMU-MP-3是BTK激酶的ATP竞争型小分子抑制剂，可选择性地抑制BTK...B-cell malignancies derive from the uncontrolled growth of lymphocytic B cells. Bruton’s tyrosine kinase (BTK) is a cytoplasmic non-recepter tyrosine kinase, which is a member of TEC kinase family. Expression and activation of BTK is crucial for cell proliferation and survival in various B cell malignancies, which suggest BTK is an ideal target in B-cell malignancies. Here we report the identific...学位：理学博士院系专业：生命科学学院_微生物学学号：2162012015378