University of Pittsburgh researchers have identified a pipeline of novel anticancer agents with dual action on cell proliferation and EMT. C19 is a promising small molecule candidate with remarkable inhibitor activity against Hippo, Wnt and TGF-beta pathways: it induces TAZ degradation through activation (phosphorylation) of Hippo kinases MST/LATS and the tumor suppressor kinase AMPK, which is an upstream regulator of the degradation complex of YAP.
Description
A common cause of both cancer metastasis and resistance to therapy is the epithelial-mesenchymal transition (EMT), which endows cancer cells with superior ability to survive drug toxicity and migrate to distant sites. Wnt, TGF-beta, and Hippo signaling pathways represent the major inducers of EMT; targeting all three simultaneously could represent an effective way to suppress cancer progression. Because EMT pathways are also implicated in organ fibrosis and neuropathic pain, pan-EMT inhibitors may have an application in treating these disorders as well.
Applications
• Pan-EMT inhibitor to treat cancer and other EMT associated diseases
• Potential drug candidate to treat organ fibrosis and neuropathic pain
Advantages
• Inhibits tumor growth by 90%
• Prevents recurrence of cancer
• No detectable toxicity
• Inhibits resistance of cancer cells to therapy
• Inhibits expression of pro-fibrotic markers and activates anti-obesity, anti-diabetic, and anti-fibrosis enzyme AMPK
Invention Readiness
C19 has completed key drug development steps including lead optimization, mechanism of action, target identification and proof of concept in animal models. Collaborations to validate its efficacy in cancer patients are awaited.
IP Status
https://patents.google.com/patent/US9649300B2
