Apelin-Receptor (APJ) Antagonist

­A series of stable, small molecule compounds that inhibit an alternative (non-VEGF) angiogenic pathway that is overexpressed in a variety of cancers. Background: Antiangiogenic drugs are commonly used to treat solid tumors and various eye condit…

­A series of stable, small molecule compounds that inhibit an alternative (non-VEGF) angiogenic pathway that is overexpressed in a variety of cancers. Background: Antiangiogenic drugs are commonly used to treat solid tumors and various eye conditions (e.g. wet AMD).  The major target of most clinically approved anti-angiogenic monoclonal antibodies and small molecules drugs is the vascular endothelial growth factor (VEGF) signaling pathway.  However, the therapy-induced alteration of blood vessels resulting from the use of anti-VEGF therapies has been shown to cause not only local hypoxia but also a stimulus for expression of alternative angiogenic pathways that render these therapies less effective over time, as well as a selection pressure for more invasive cancer cells that lead to metastasis.  One such alternative pathway that shows promise as a target for therapy is that of the apelin receptor (APJ), which is overexpressed in a wide variety of cancers and contributes to pathogenesis through angiogenesis, metastasis, and cell proliferation.  When combined with anti-VEGF therapy-associated metastasis, as well as improve blood vessel structure, and enables more uniform delivery of other anticancer therapies into the tumor.  Despite its promising inhibitory effects, ML221, the leading anti-APJ small molecule to date, has demonstrated poor stability, thus preventing its development as a viable drug candidate. Technology Overview: This invention provides a series of small molecule anti-APJ antagonists that overcome the key problems (metabolic instabilities and thus short plasma half-life) seen with ML221.  Testing to date has revealed that at least three of these compounds possess superior metabolic stability and longer plasma half-life than ML221.  Advantages:

  • Superior stability (vs. ML221)
  • Ability to be administered orally
  • Improved ability to cross blood-brain-barrier (vs. biologics)

Applications:

  • Oncology (glioblastoma, cancers of the lung, breast kidney, colon, and rectum)
  • Eye disease (wet AMD, diabetic retinopathy, corneal neovascularization)

Intellectual Property Summary: US Provisional Patent Application 63/287,053 filed December 7, 2021. Stage of Development: in vitro Licensing Status: Available for licensing or collaboration.

Website

https://suny.technologypublisher.com/tech/Apelin-Receptor_(APJ)_Antagonist

Contact Information

TTO Home Page: https://suny.technologypublisher.com

Name: Timothy Dee

Title: Associate Director

Email: tpdee@buffalo.edu

Phone: 716-645-8139