VIT-2763 是具有口服活性的铁转运蛋白 (ferroportin) 的抑制剂,抑制hepcidin 与铁转运蛋白结合,阻滞铁外流。VIT-2763有用于地中海贫血症的潜力。
生物活性 | VIT-2763, an oralferroportininhibitor, inhibits hepcidin binding toferroportinand blocks iron efflux. VIT-2763 has the potential in the treatment of β-thalassemia[1]. |
体外研究 (In Vitro) | VIT-2763 dose dependently reduces the fluorescence polarization signal, indicating that VIT-2763 displaces TMR-hepcidin from ferroportin (IC50of 24 ± 13 nM)[1]. VIT-2763 induces BLA reporter gene activity with an average EC50of 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].
Cell Viability Assay[1]. Cell Line: | J774 cells. | Concentration: | 100 nM. | Incubation Time: | 10, 20, 40, 60, or 120 minutes. | Result: | Induced ferroportin internalization and ubiquitination. |
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体内研究 (In Vivo) | 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].
Animal Model: | Hbbth3/+mice[1].
| Dosage: | 30, 100 mg/kg. | Administration: | Orally twice daily for 36 days. | Result: | Significantly decreased serum iron levels by 77% (30 mg/kg) and 84% (100 mg/kg), Significantly increased Hb levels (as of day 8 of treatment), RBC counts, mean corpuscular Hb concentration (MCHC), and significantly 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.
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 125 mg/mL(306.05 mM;Need ultrasonic) 配制储备液 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 |
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此方案可获得 ≥ 2.08 mg/mL (5.09 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (5.09 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.09 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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