The Biology Behind the Apelin Receptor Agonist
The Apelinergic Signaling Pathway
The Apelinergic System (Apelin receptor, APJ) plays a vital role in repair and regeneration of the micro vascular niche and is well-established as an endogenous anti-injury and organ-protective pathway regulating:
- Vascular function
- Fluid homeostasis
- Adipose tissue function
- Angiogenesis / inotropy
Apelin is a selective endogenous ligand for the G protein-coupled receptor APJ, which is expressed ubiquitously with elevated levels in vascular endothelial cells, cardiomyocytes and vascular smooth muscle cells, and lower levels in keratinocytes and fibroblasts. In response to tissue injury, APJ signaling induces endothelial cell proliferation, differentiation, polarization, and migration, leading to vascular repair and regeneration. The Apelin receptor (APJ) is expressed in various organs (brain, skin, heart, kidney, liver and lungs) in the vascular endothelium niche, which is critical to the delivery of nutrients, oxygen, and cellular components to the local tissue as well as the removal of waste products from the tissue.
Stimulating the Apelin-APJ pathway activates an organ protective and regenerative response
The Apelin-APJ signaling pathway in the vascular niche is biologically activated to protect and promote self-repair after injury. However, uncontrolled injuries such as viral infections, genetics and others can overwhelm the biological pathway leading to the disruption of multiple other biological pathways that results in chronic inflammation, fibrosis, and tissue damage.
Apelin-APJ signaling pathway activation leads to vascular niche repair
APJ signaling induces endothelial and epithelial cell proliferation, differentiation, polarization, and migration, leading to vascular niche repair and regeneration. It is now well-established that targeting the vascular niche after injury promotes repair and reduces the proliferation of downstream pathophysiology that may results in permanent organ damage.
Apelin-APJ signaling pathway activation leads to vascular niche repair
APJ signaling induces endothelial and epithelial cell proliferation, differentiation, polarization, and migration, leading to vascular niche repair and regeneration. It is now well-established that targeting the vascular niche after injury promotes repair and reduces the proliferation of downstream pathophysiology that may results in permanent organ damage.
Apelin-APJ signaling is a therapeutic mechanism for multiple indications
Following the biology of various disease pathophysiology appears to indicate that Apelin-APJ receptor activation could be a potential mechanism of action and a cutting-edge pathway for best-in-class therapies.
Apelin Receptor / APJ Agonist Platform Potential
Pulmonary
- Idiopathic Pulmonary Fibrosis (IPF)
- Pulmonary Artery Hyperextension (PAH)
- Acute Respiratory Distress Syndrome (ARDS)
Renal
- Kidney Nephrotic Syndrome
- Focal Segmental Glomerulosclerosis (FSGS)
Cardiac and Metabolic
- Heart Failure (HF)
- Non-Alcoholic Steatosis Hepatitis (NASH / NAFLD)
- Abdominal Aortic Aneurysm (AAA)
- Primary Sclerosing Cholangitis (PSC)
Dermal
- Scleroderma (SSc)
Proof of biology for APIE-T Apelin-APJ agonists
We have conducted extensive primary pharmacology (in addition to pharmacological safety profiling) via validated animal models studies in chronic diseases such as Idiopathic Pulmonary Fibrosis, Heart Failure and Metabolic Syndrome. In all studies, Apelin-APJ Agonist have shown pre-clinical efficacy in the studies end point:
- Idiopathic Pulmonary Fibrosis (APT101)
- Heart Failure (APT101 and APT102)
- Metabolic Syndrome (Liver Steatosis, Glucose Tolerance, Weight Loss; APT103)
In addition, a comprehensive ex-human in-vitro study confirmed APT101 as biologically active with primary pharmacology in tissue remodeling, hemostasis, inflammation, immunomodulatory activities, renal markers, and fibrosis.
