Activin receptor-like kinase 1 (ALK1) (ALK1)

Activin receptor-like kinase 1 (ALK1) is a type I cell-surface receptor belonging to the transforming growth factor-beta (TGF-beta) superfamily, primarily expressed on vascular endothelial cells (UniProt: P37023). It plays a critical role in regulating angiogenesis and vascular remodeling by signaling through the Smad1/5/8 pathway upon activation by its ligands, bone morphogenetic protein 9 (BMP9) and BMP10 (PubMed: 22431068). In the context of oncology, ALK1 is a therapeutic target because its signaling promotes tumor-associated angiogenesis, which supports tumor growth and metastasis (PubMed: 24583793). PF-03446962 (Balanocimab) is a fully human monoclonal antibody designed to bind specifically to the extracellular domain of ALK1, thereby blocking ligand interaction and inhibiting the pro-angiogenic signaling cascade (ClinicalTrials.gov: NCT00432744). Beyond cancer, mutations in the ACVRL1 gene are the primary cause of Hereditary Hemorrhagic Telangiectasia type 2 (HHT2), a disorder characterized by vascular malformations (PubMed: 11433322). Therapeutic targeting of ALK1 provides an alternative mechanism to VEGF inhibition for controlling tumor blood vessel formation, though it is associated with specific safety concerns such as hypertension and epistaxis.

Other names

ACVRL1Serine/threonine-protein kinase receptor R3SKR3HHT2ORW2TGF-beta superfamily receptor type I

Inhibition of ALK1 signaling by binding to the extracellular domain and blocking BMP9/10 ligand interaction, thereby suppressing Smad1/5/8-mediated pro-angiogenic gene expression.