Therapeutics: Notch 1 (NOTCH1); jagged 1 (JAG1); jagged 2 (JAG2)

In vitro and mouse studies suggest inhibiting JAG-mediated NOTCH1 signaling could help treat cancer by inhibiting angiogenesis. In an in vitro angiogenesis assay, human endothelial cells expressing NOTCH1 decoy proteins that inhibited binding of JAG1 and JAG2 to NOTCH1 decreased angiogenesis compared with a control protein. In mice, the decoy proteins decreased retinal angiogenesis and blood vessel density compared with inactive control proteins. In mouse tumor xenograft models, the decoy proteins decreased angiogenesis and tumor growth compared with control proteins. Next steps could include identifying small molecules that block JAG-NOTCH1 binding.

At least four companies have inhibitors or antibodies against NOTCH1 in Phase I or earlier testing to treat cancers...