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 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 leads 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, anti-APJ therapy has been shown to prevent or reduce the occurrence of anti-VEGF therapy-associated metastasis as well as improve blood vessel structure, which 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 University at Buffalo 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.

Stage of Development

In vitro.

Benefits

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)

Opportunity

Available for licensing or collaboration.

Apelin-Receptor (APJ) Antagonists

Patents

IP Status

Seeking