VIT-2763 is an orally bioactive inhibitor of ferroportin, which inhibits/disrupts the binding of hepcidin to ferroportin and blocks iron efflux. VIT-2763 has potential for thalassemia.

Physicochemical Properties

Molecular Formula	C21H21FN6O2
Molecular Weight	408.428847074509
Exact Mass	408.171
CAS #	2095668-10-1
PubChem CID	129052159
Appearance	Off-white to light yellow solid powder
LogP	1.9
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	9
Heavy Atom Count	30
Complexity	556
Defined Atom Stereocenter Count	0
SMILES	FC1=CC=CN=C1CNC(C1=COC(CCNCCC2=NC3C=CC=CC=3N2)=N1)=O
InChi Key	KNYVRFXIVWUGBZ-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	2-[2-[2-(1H-benzimidazol-2-yl)ethylamino]ethyl]-N-[(3-fluoropyridin-2-yl)methyl]-1,3-oxazole-4-carboxamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	The fluorescence polarization signal is dose-dependently reduced by VIT-2763, suggesting that VIT-2763 displaces TMR-hepcidin from ferroportin (IC50 of 24 ± 13 nM)[1]. The BLA reporter gene is activated by VIT-2763, with an average EC50 of 140 ± 50 nM, in response to elevated intracellular iron concentrations in HEK293 cells from restricted iron export[1]. Ferroportin is ubiquitinated at 100 nM, which causes ferroportin to internalize and degrade[1].
ln Vivo	In Hbbth3/+ mice, VIT-2763 (30, 100 mg/kg, orally twice daily for 36 days) reduces serum iron levels and prevents hepatic iron loading[1]. The total iron in the liver was not altered by VIT-2763[1]. In Hbbth3/+ mice, oral VIT-2763 (30, 100 mg/kg) taken twice a day for 36 days dramatically corrects anemia and improves RBC parameters. In Hbbth3/+ mice, VIT-2763 reduces the proportion of ROS-positive RBCs from 67% to 30%[1]. In Hbbth3/+ mice, VIT-2763 prolongs RBC life and reduces apoptosis[1].
Cell Assay	Cell Viability Assay[1]. Cell Types: J774 cells. Tested Concentrations: 100 nM. Incubation Duration: 10, 20, 40, 60, or 120 minutes. Experimental Results: Induced ferroportin internalization and ubiquitination.
Animal Protocol	Animal/Disease Models: Hbbth3/+ mice[1]. Doses: 30, 100 mg/kg. Route of Administration: Orally twice (two times) daily for 36 days. Experimental Results: Dramatically diminished serum iron levels by 77% (30 mg/kg) and 84% (100 mg/kg), Dramatically increased Hb levels (as of day 8 of treatment), RBC counts, mean corpuscular Hb concentration (MCHC), and Dramatically lowered reticulocyte counts, mean corpuscular Hb (MCH), mean corpuscular volume (MCV), and RBC distribution width (RDW) in Hbbth3/+ mice, as compared with the Hbbth3/+ vehicle group.
References	[1]. Oral Ferroportin Inhibitor Ameliorates Ineffective Erythropoiesis in a Model of β-Thalassemia. J Clin Invest. 2019 Dec 9;130(1):491-506.
Additional Infomation	Vamifeport is being investigated for the treatment of beta-thalassemia.

Solubility Data

Solubility (In Vitro)

DMSO: 83.33 mg/mL (204.03 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4484 mL	12.2420 mL	24.4840 mL
	5 mM	0.4897 mL	2.4484 mL	4.8968 mL
	10 mM	0.2448 mL	1.2242 mL	2.4484 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.