VIT-2763 is an oral, small-molecule ferroportin inhibitor that reduces serum iron and transferrin saturation (TSAT) levels [1]. VIT-2763 competes with hepcidin for binding to ferroportin, displacing hepcidin bound to recombinant ferroportin, and reducing cellular iron efflux [2]. VIT-2763 has been widely used to reduce the amount of early erythroid precursors in the bone marrow and spleen, and increase the number of mature erythrocytes [3].
In vitro, VIT-2763 treatment for 15 minutes significantly inhibited the internalization of fluorescently labeled hepcidin (TMR-hepcidin) in J774 cells, with an IC50 value of 9nM[4].
In vivo, VIT-2763 treatment via oral administration at a dose of 30mg/kg/day for 7 days exacerbated Plasmodium infection in mice and enhanced inflammatory responses and liver injury[5]. Daily administration of water containing 1mg/ml VIT-2763 for 10 weeks significantly reduced the spleen enlargement and alleviated systemic lupus nephritis in MRL/lpr mice[6]. Oral administration of VIT-2763 at a dose of 30mg/kg/day for 3 weeks improved anemia and erythropoiesis in a mouse model of β-thalassemia[7]. Daily intragastric administration of a 240mg/kg dose of VIT-2763 was carried out for 3 months, which significantly alleviated the cardiopulmonary dysfunction in the subchronic moderate hypoxia model of Berkeley SCD mice[8].
References:
[1] Kattamis A, Taher A, Viprakasit V, et al. Safety and pharmacodynamics of the ferroportin inhibitor vamifeport in patients with non-transfusion-dependent β-thalassemia: results from a randomized phase 2a study[J]. Orphanet Journal of Rare Diseases, 2025, 20(1): 608.
[2] Porter J, Taher A, Viprakasit V, et al. Oral ferroportin inhibitor vamifeport for improving iron homeostasis and erythropoiesis in β-thalassemia: current evidence and future clinical development[J]. Expert Review of Hematology, 2021, 14(7): 633-644.
[3] Pilo F, Angelucci E. Vamifeport: monography of the first oral ferroportin inhibitor[J]. Journal of Clinical Medicine, 2024, 13(18): 5524.
[4] Manolova V, Nyffenegger N, Flace A, et al. Oral ferroportin inhibitor ameliorates ineffective erythropoiesis in a model of β-thalassemia[J]. The Journal of clinical investigation, 2020, 130(1): 491-506.
[5] Zeydabadinejad S, Theis B F, Park J S, et al. Pharmacologic Inhibition of Erythrocyte Ferroportin Expression Exacerbates Plasmodium Infection[J]. Microorganisms, 2025, 13(8): 1859.
[6] Katikaneni D, Arekar T, Al-Hraki L, et al. Vamifeport, a clinical stage oral ferroportin inhibitor, alleviates murine lupus nephritis: A pilot study[J]. Clinical Immunology, 2026: 110699.
[7] Nyffenegger N, Flace A, Doucerain C, et al. The oral ferroportin inhibitor VIT-2763 improves erythropoiesis without interfering with iron chelation therapy in a mouse model of β-thalassemia[J]. International journal of molecular sciences, 2021, 22(2): 873.
[8] Lucero M J, Setua S, Thangaraju K, et al. Ferroportin inhibition attenuates pulmonary hypertension in hypoxic sickle cell disease mice[J]. Blood Advances, 2026, 10(9): 3229-3242.