RGD-binding integrin receptors (RGD integrins)

RGD-binding integrin receptors are a specialized subset of the integrin family consisting of eight heterodimeric transmembrane proteins—Integrin alpha-V beta-1, Integrin alpha-V beta-3, Integrin alpha-V beta-5, Integrin alpha-V beta-6, Integrin alpha-V beta-8, Integrin alpha-5 beta-1, Integrin alpha-8 beta-1, and Integrin alpha-IIb beta-3—that recognize the Arginine-Glycine-Aspartic acid (RGD) tripeptide motif in extracellular matrix (ECM) ligands [1][2]. These receptors function as bidirectional signaling hubs, mediating cell-matrix adhesion and regulating essential cellular processes such as migration, proliferation, and survival [3]. In pathological conditions, pan-RGD integrins are frequently overexpressed; for example, Integrin alpha-V beta-3 and Integrin alpha-V beta-5 facilitate tumor-associated angiogenesis, while Integrin alpha-V beta-6 and Integrin alpha-V beta-1 are critical for the activation of latent TGF-beta in fibrotic diseases [4][5]. Therapeutic interventions targeting these receptors often utilize RGD-mimetic small molecules or cyclic peptides to competitively inhibit ligand binding [6]. While targeting multiple RGD-binding integrins (a "pan-RGD" approach) can provide synergistic therapeutic effects in complex diseases like idiopathic pulmonary fibrosis or metastatic cancer, it also carries risks such as impaired hemostasis and bleeding due to the inhibition of the platelet-specific Integrin alpha-IIb beta-3 [7].

Other names

pan-RGD integrinsRGD-recognizing integrinsArg-Gly-Asp binding integrinsRGD-dependent integrins

Competitive antagonism of the Arg-Gly-Asp (RGD) binding site on the integrin alpha subunit, preventing interaction with extracellular matrix ligands and inhibiting downstream signaling or TGF-beta activation.