ADGRD1/GPR133 Adhesion Receptor Antibodies

ADGRD1, also known as GPR133, is an adhesion class GPCR with a characteristic extracellular GAIN domain and a tethered Stachel sequence that can function as an endogenous agonist following receptor activation or conformational changes. The receptor predominantly couples to Gs proteins and stimulates adenylyl cyclase, resulting in increased intracellular cAMP and activation of downstream PKA-dependent signaling. ADGRD1 is expressed in several tissues, with particularly important expression reported in bone cells and skeletal muscle, while its expression is strongly upregulated under hypoxic conditions in glioblastoma. In glioblastoma, ADGRD1 is enriched in tumor stem-like cells and hypoxic tumor regions and appears to promote tumor-cell proliferation and tumor growth. In the skeletal system, ADGRD1 signaling promotes osteoblast differentiation and bone formation and has also been shown to suppress osteoclastogenesis, indicating an important role in bone homeostasis. Recent studies have identified 5α-dihydrotestosterone as an agonist of ADGRD1 and demonstrated that androgen-dependent receptor activation can increase cAMP signaling and enhance skeletal muscle strength. Several synthetic agonists have now been described, including AP503 (AP-970/43482503), a potent and selective Gs-biased agonist, and GL64, which activates ADGRD1 through the receptor’s Stachel-binding pocket. AP503 and GL64 have shown beneficial effects in experimental models of osteoporosis, including increased bone formation and reduced bone loss. No approved drug or clinical-stage therapeutic targeting ADGRD1 is currently available, but the receptor has emerged as a promising pharmacological target for osteoporosis, muscle disorders and potentially glioblastoma. For more information on ADGRD1 pharmacology please refer to the IUPHAR database. For further reading refer to:

Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B et al.. (2015) International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev, 67 (2): 338-67.