VIT-2763

• CAT Number: I015381
• CAS Number: 2095668-10-1
• Molecular Formula: C21H21FN6O2
• Molecular Weight: 408.43
• Purity: ≥95%
• Synonyms: 2-[2-[2-(1H-benzimidazol-2-yl)ethylamino]ethyl]-N-[(3-fluoropyridin-2-yl)methyl]-1,3-oxazole-4-carboxamide
• InChI: InChI=1S/C21H21FN6O2/c22-14-4-3-9-24-17(14)12-25-21(29)18-13-30-20(28-18)8-11-23-10-7-19-26-15-5-1-2-6-16(15)27-19/h1-6,9,13,23H,7-8,10-12H2,(H,25,29)(H,26,27)
• InChIKey: KNYVRFXIVWUGBZ-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)NC(=N2)CCNCCC3=NC(=CO3)C(=O)NCC4=C(C=CC=N4)F

VIT-2763, an oral ferroportin inhibitor, inhibits hepcidin binding to ferroportin and blocks iron efflux. VIT-2763 has the potential in the treatment of β-thalassemia[1].
VIT-2763 dose dependently reduces the fluorescence polarization signal, indicating that VIT-2763 displaces TMR-hepcidin from ferroportin (IC50 of 24 ± 13 nM)[1].
VIT-2763 induces BLA reporter gene activity with an average EC50 of 140 ± 50 nM, as a consequence of increasing intracellular iron concentrations caused by blocked iron export in HEK293 cells[1].
VIT-2763 (100 nM) triggers ubiquitination and subsequent internalization and degradation of ferroportin[1].
VIT-2763 (30, 100 mg/kg, orally twice daily for 36 days) decreases serum iron and prevented liver iron loading in Hbbth3/+ mice[1].
VIT-2763 did not change the total liver iron[1].
VIT-2763 (30, 100 mg/kg, orally twice daily for 36 days) significantly corrects anemia and improved RBC parameters in Hbbth3/+ mice. VIT-2763 decreases the percentage of ROS-positive RBCs in Hbbth3/+ mice from 67% to 30%[1].
VIT-2763 decreases apoptosis and extends the life span of RBCs in Hbbth3/+ mice[1].

Reference

[1]. Vania Manolova, et al. Oral Ferroportin Inhibitor Ameliorates Ineffective Erythropoiesis in a Model of β-Thalassemia. J Clin Invest. 2019 Dec 9;130(1):491-506.
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