VcMMAE (mc-vc-PAB-MMAE) 是一種生化試劑,是抗體藥物復(fù)合體的一部分 (drug-linker conjugate for ADC),具有抗癌活性,它由 MMAE (一種 tubulin 抑制劑) 和 Vc 連接而成。
VcMMAE(mc-vc-PAB-MMAE)是ADC的藥物連接物偶聯(lián)物,通過使用抗核分裂劑單甲基auristatin E(MMAE,微管蛋白抑制劑),通過溶酶體可裂解的二肽,纈氨酸- 瓜氨酸(vc)。
單甲基耳他汀E(MMAE)可從CD30 +癌細胞內(nèi)的SGN-35有效釋放,并且由于其膜通透性,能夠?qū)ε杂^者細胞發(fā)揮細胞毒活性。 MMAE以與有絲分裂阻滯相關(guān)的時間表和劑量依賴性方式使大腸和胰腺癌細胞對IR敏感。 放療后克隆形成存活率降低和DNA雙鏈斷裂增加證明了放射增敏。
單甲基澳瑞他汀E(MMAE)與IR結(jié)合會導(dǎo)致腫瘤生長延遲,在異種移植模型中,以IR靶向腫瘤的ACPP-cRGD-MMAE會產(chǎn)生更穩(wěn)定且顯著延長的腫瘤消退。
Auristatin
Monomethyl auristatin E (MMAE) is efficiently released from SGN-35 within CD30 + cancer cells and, due to its membrane permeability, is able to exert cytotoxic activity on bystander cells. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule and dose dependent manner correlating with mitotic arrest. Radiosensitization is evidenced by decreased clonogenic survival and increased DNA double strand breaks in irradiated cells.
Monomethyl auristatin E (MMAE) in combination with IR results in tumor growth delay, tumor-targeted ACPP-cRGD-MMAE with IR produces a more robust and significantly prolonged tumor regression in xenograft models.