β-Glu-PAB(CH2NH2)-Exatecan (Compound 9a) is atopoisomeraseIinhibitor. β-Glu-PAB(CH2NH2)-Exatecan binds to thetopoisomeraseI-DNA complex to prevent DNA strand reconnection, thereby inducing DNA breakage and cellapoptosis. β-Glu-PAB(CH2NH2)-Exatecan can be specifically cleaved byβ-glucuronidasehighly expressed in the tumor microenvironment to release Exatecan for cytotoxic effect. β-Glu-PAB(CH2NH2)-Exatecan is also an intermediate of Mal((3S,3aR,6S,6aR) -hexahydrofuro [3, 2-B]furan-3,6-diamine-PEG12)-β -Glu-Pab-Exatecan. β-Glu-PAB(CH2NH2)-Exatecan is promising for research of cancers[1].
References:
[1].krishna BAJJURI, et al. β-GLUCURONIDE LINKER-PAYLOADS, PROTEIN CONJUGATES THEREOF, AND METHODS THEREOF. WO2024006272A1. 2024-09-26.
β-Glu-PAB(CH2NH2)-Exatecan (Compound 9a) 是一种拓扑异构酶 I (topoisomeraseI) 的抑制剂。β-Glu-PAB(CH2NH2)-Exatecan 与拓扑异构酶 I-DNA 复合物结合，阻止 DNA 链的重新连接，从而诱导 DNA 断裂和细胞凋亡。β-Glu-PAB(CH2NH2)-Exatecan 可被肿瘤微环境中高表达的 β- 葡萄糖醛酸酶特异性切割，释放出 Exatecan 发挥细胞毒作用。β-Glu-PAB(CH2NH2)-Exatecan 也是 Mal((3S,3aR,6S,6aR)-Hexahydrofuro[3,2-b]furan-3,6-diamine-PEG12)-β-Glu-PAB-Exatecan 的中间体。β-Glu-PAB(CH2NH2)-Exatecan 有望用于癌症的研究。