Distinct binding and signaling activity of Acthar Gel compared to other melanocortin receptor agonists

References

• Gantz I, Fong TM. The melanocortin system. Am J Physiol Endocrinol Metab. 2003;284(3):E468–E474.
   PubMed Web of Science ®Google Scholar
• Dores RM, Londraville RL, Prokop J, et al. Molecular evolution of GPCRs: melanocortin/melanocortin receptors. J Mol Endocrinol. 2014;52(3):T29–T42.
   PubMedGoogle Scholar
• Mykicki N, Herrmann AM, Schwab N, et al. Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. Sci Transl Med. 2016;8(362):362ra146
   PubMed Web of Science ®Google Scholar
• Zhang L, Dong L, Liu X, et al. α-Melanocyte-stimulating hormone protects retinal vascular endothelial cells from oxidative stress and apoptosis in a rat model of diabetes. PLoS One. 2014;9(4):e93433
   PubMed Web of Science ®Google Scholar
• Catania A, Lonati C, Sordi A, et al. The melanocortin system in control of inflammation. ScientificWorldJournal. 2010;10:1840–1853.
   PubMed Web of Science ®Google Scholar
• Chai B, Li JY, Zhang W, et al. Melanocortin-4 receptor-mediated inhibition of apoptosis in immortalized hypothalamic neurons via mitogen-activated protein kinase. Peptides. 2006;27(11):2846–2857.
   PubMed Web of Science ®Google Scholar
• Lisak RP, Benjamins JA. Melanocortins, melanocortin receptors and multiple sclerosis. Brain Sci. 2017;7(8):104.
   Web of Science ®Google Scholar
• Fridmanis D, Roga A, Klovins J. ACTH receptor (MC2R) specificity: what do we know about underlying molecular mechanisms? Front Endocrinol (Lausanne). 2017;8:13
   PubMed Web of Science ®Google Scholar
• Catania A, Gatti S, Colombo G, et al. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004;56(1):1–29.
   PubMed Web of Science ®Google Scholar
• Nakanishi S, Inoue A, Kita T, et al. Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor. Nature. 1979;278(5703):423–427.
   PubMed Web of Science ®Google Scholar
• Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27(7):736–749.
   PubMed Web of Science ®Google Scholar
• Li ZX, Liu BW, He ZG, et al. Melanocortin-4 receptor regulation of pain. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt A):2515–2522.
   PubMed Web of Science ®Google Scholar
• Arnason BG, Berkovich R, Catania A, et al. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis. Mult Scler. 2013;19(2):130–136.
   PubMed Web of Science ®Google Scholar
• Hinkle PM, Sebag JA. Structure and function of the melanocortin2 receptor accessory protein (MRAP). Mol Cell Endocrinol. 2009;300(1–2):25–31.
   PubMed Web of Science ®Google Scholar
• Rodrigues AR, Almeida H, Gouveia AM. Intracellular signaling mechanisms of the melanocortin receptors: current state of the art. Cell Mol Life Sci. 2015;72(7):1331–1345.
   PubMed Web of Science ®Google Scholar
• Roy S, Rached M, Gallo-Payet N. Differential regulation of the human adrenocorticotropin receptor [melanocortin-2 receptor (MC2R)] by human MC2R accessory protein isoforms alpha and beta in isogenic human embryonic kidney 293 cells. Mol Endocrinol. 2007;21(7):1656–1669.
   PubMedGoogle Scholar
• Sebag JA, Hinkle PM. Regions of melanocortin 2 (MC2) receptor accessory protein necessary for dual topology and MC2 receptor trafficking and signaling. J Biol Chem. 2009;284(1):610–618.
   PubMed Web of Science ®Google Scholar
• Nussdorfer GG, Mazzocchi G, Malendowicz LK. Acute effects of alpha-MSH on the rat zona glomerulosa in vivo. Biochem Biophys Res Commun. 1986;141(3):1279–1284.
   PubMed Web of Science ®Google Scholar
• Shenker Y, Villareal JZ, Sider RS, et al. Alpha-melanocyte-stimulating hormone stimulation of aldosterone secretion in hypophysectomized rats. Endocrinology. 1985;116(1):138–141.
   PubMed Web of Science ®Google Scholar
• Catania A. Neuroprotective actions of melanocortins: a therapeutic opportunity. Trends Neurosci. 2008;31(7):353–360.
   PubMed Web of Science ®Google Scholar
• Patel HB, Bombardieri M, Sampaio ALF, et al. Anti-inflammatory and antiosteoclastogenesis properties of endogenous melanocortin receptor type 3 in experimental arthritis. Faseb J. 2010;24(12):4835–4843.
   PubMed Web of Science ®Google Scholar
• Patel HB, Leoni G, Melendez TM, et al. Melanocortin control of cell trafficking in vascular inflammation. Adv Exp Med Biol. 2010;681:88–106.
   PubMed Web of Science ®Google Scholar
• Acthar Gel [package insert]. Bedminster (NJ): Mallinckrodt ARD LLC; 2019.
   Google Scholar
• Olsen NJ, Decker DA, Higgins P, et al. Direct effects of HP Acthar Gel on human B lymphocyte activation in vitro. Arthritis Res Ther. 2015;17:300.
   PubMed Web of Science ®Google Scholar
• Wright D, Zweifel B, Sharma P, et al. Reduced steroidogenic activity of repository corticotropin injection (RCI) induces a distinct cytokine response following T cell activation in vivo (abstract AB0082). Ann Rheum Dis. 2019;78(suppl 2):1504.
   Web of Science ®Google Scholar
• Benko AL, McAloose CA, Becker PM, et al. Repository corticotrophin injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids. Clin Exp Immunol. 2018;192(1):68–81.
   PubMed Web of Science ®Google Scholar
• Philbin M, Niewoehner J, Wan GJ. Clinical and economic evaluation of repository corticotropin injection: a narrative literature review of treatment efficacy and healthcare resource utilization for seven key indications. Adv Ther. 2017;34(8):1775–1790.
   PubMed Web of Science ®Google Scholar
• Decker DA, Grant C, Oh L, et al. Immunomodulatory effects of H.P. Acthar Gel on B cell development in the NZB/W F1 mouse model of systemic lupus erythematosus. Lupus. 2014;23(8):802–812.
   PubMed Web of Science ®Google Scholar
• Brod SA, Bauer V, Hood Z. Oral ACTH (H.P. Acthar(®)Gel) inhibits IL-1 and IL-17 secretion in humans. Biomed Pharmacother. 2012;66(1):36–39.
   PubMed Web of Science ®Google Scholar
• Decker D. Repository corticotropin injection attenuates collagen-induced arthritic joint structural damage and has enhanced effects in combination with etanercept. 2020. https://bmcmusculoskeletdisord.biomedcentral.com/.
   Google Scholar
• Hayes K, Warner E, Bollinger C, et al. Repository corticotropin injection versus corticosteroids for protection against renal damage in a focal segmental glomerulosclerosis rodent model. BMC Nephrol. 2020;21(1):226.
   PubMed Web of Science ®Google Scholar
• Ross AP, Ben-Zacharia A, Harris C, et al. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone. Front Neurol. 2013;4:21.
   PubMed Web of Science ®Google Scholar
• Penhoat A, Naville D, El Mourabit H, et al. Functional expression of the human ACTH receptor gene. Endocr Res. 2000;26(4):549–557.
   PubMed Web of Science ®Google Scholar
• National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the care and use of laboratory animals. 8th ed. Washington (DC): National Academies Press (US); 2011.
   Google Scholar
• Chida D, Nakagawa S, Nagai S, et al. Melanocortin 2 receptor is required for adrenal gland development, steroidogenesis, and neonatal gluconeogenesis. Proc Natl Acad Sci USA. 2007;104(46):18205–18210.
   PubMed Web of Science ®Google Scholar
• Pritchard LE, Armstrong D, Davies N, et al. Agouti-related protein (83–132) is a competitive antagonist at the human melanocortin-4 receptor: no evidence for differential interactions with pro-opiomelanocortin-derived ligands. J Endocrinol. 2004;180(1):183–191.
   PubMed Web of Science ®Google Scholar
• Schiöth HB, Muceniece R, Larsson M, et al. The melanocortin 1, 3, 4 or 5 receptors do not have a binding epitope for ACTH beyond the sequence of alpha-MSH. J Endocrinol. 1997;155(1):73–78.
   PubMed Web of Science ®Google Scholar
• Kapas S, Cammas FM, Hinson JP, et al. Agonist and receptor binding properties of adrenocorticotropin peptides using the cloned mouse adrenocorticotropin receptor expressed in a stably transfected HeLa cell line. Endocrinology. 1996;137(8):3291–3294.
   PubMed Web of Science ®Google Scholar
• Chen M, Aprahamian CJ, Kesterson RA, et al. Molecular identification of the human melanocortin-2 receptor responsible for ligand binding and signaling. Biochemistry. 2007;46(40):11389–11397.
   PubMed Web of Science ®Google Scholar
• Berkovich R, Agius MA. Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis. Ther Adv Neurol Disord. 2014;7(2):83–96.
   PubMed Web of Science ®Google Scholar
• Nazareth T, Datar M, Yu TC. Treatment effectiveness for resolution of multiple sclerosis relapse in a US health plan population. Neurol Ther. 2019;8(2):383–395.
   PubMed Web of Science ®Google Scholar
• Baram TZ, Mitchell WG, Tournay A, et al. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996;97(3):375–379.
   PubMed Web of Science ®Google Scholar
• Brunson KL, Khan N, Eghbal-Ahmadi M, et al. Corticotropin (ACTH) acts directly on amygdala neurons to down-regulate corticotropin-releasing hormone gene expression. Ann Neurol. 2001;49(3):304–312.
   PubMed Web of Science ®Google Scholar
• Bergwall L, Wallentin H, Elvin J, et al. Amplification of the melanocortin-1 receptor in nephrotic syndrome identifies a target for podocyte cytoskeleton stabilization. Sci Rep. 2018;8(1):15731.
   PubMedGoogle Scholar
• Gaitonde SA, González-Maeso J. Contribution of heteromerization to G protein-coupled receptor function. Curr Opin Pharmacol. 2017;32:23–31.
   PubMed Web of Science ®Google Scholar
• Yang Y, Mishra V, Crasto CJ, et al. Third transmembrane domain of the adrenocorticotropic receptor is critical for ligand selectivity and potency. J Biol Chem. 2015;290(12):7685–7692.
   PubMed Web of Science ®Google Scholar
• Yasir M, Sonthalia S. Corticosteroid adverse effects. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 [Updated 2019 Oct 1]. https://www.ncbi.nlm.nih.gov/books/NBK531462/.
   Google Scholar
• Fleischmann R, Furst DE, Connolly-Strong E, et al. Repository corticotropin injection for active rheumatoid arthritis despite aggressive treatment: a randomized controlled withdrawal trial. Rheumatol Ther. 2020;7(2):327–344.
   PubMed Web of Science ®Google Scholar
• Bomback AS, Canetta PA, Beck LH, Jr, et al. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58–67.
   PubMed Web of Science ®Google Scholar