19A11(19A11) - 药物靶点：CDH1_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

生物药

别名-

靶点

CDH1

作用机制

CDH1拮抗剂(cadherin 1 antagonists)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

University Of California - Davis Branch (513968)

在研机构

University Of California - Davis Branch (513968)

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 19A11 相关的临床结果

登录后查看更多信息

100 项与 19A11 相关的转化医学

登录后查看更多信息

100 项与 19A11 相关的专利（医药）

登录后查看更多信息

1

项与 19A11 相关的文献（医药）

2022-08-09·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody

1区 · 综合性期刊

Article

作者: Gumbiner, Barry M. ; Sivasankar, Sanjeevi ; Maker, Allison ; Xie, Bin ; Dranow, David M. ; Edwards, Thomas E. ; Staker, Bart L. ; Myler, Peter J. ; Phan, Jenny N. ; Priest, Andrew V.

E-cadherin (Ecad) is an essential cell–cell adhesion protein with tumor suppression properties. The adhesive state of Ecad can be modified by the monoclonal antibody 19A11, which has potential applications in reducing cancer metastasis. Using X-ray crystallography, we determine the structure of 19A11 Fab bound to Ecad and show that the antibody binds to the first extracellular domain of Ecad near its primary adhesive motif: the strand–swap dimer interface. Molecular dynamics simulations and single-molecule atomic force microscopy demonstrate that 19A11 interacts with Ecad in two distinct modes: one that strengthens the strand–swap dimer and one that does not alter adhesion. We show that adhesion is strengthened by the formation of a salt bridge between 19A11 and Ecad, which in turn stabilizes the swapped β-strand and its complementary binding pocket. Our results identify mechanistic principles for engineering antibodies to enhance Ecad adhesion.

100 项与 19A11 相关的药物交易

登录后查看更多信息