voxelotor

SKU: orb1299687

Description

Voxelotor (GBT 440) is a small molecule therapeutic agent for sickle cell disease research that inhibits hemoglobin S polymerization by covalently binding to the alpha chain. It functions as a hemoglobin stabilizer and a cytochrome P450 3A4 inhibitor, with applications in both in vitro mechanistic studies and in vivo preclinical models.

Key Properties

• CAS Number: 1446321-46-5
• MW: 337.37
• Purity: 99.90%
• Formula: C₁₉H₁₉N₃O₃
• SMILES: CC(C)n1nccc1-c1ncccc1COc1cccc(O)c1C=O
• Target: Others
• Solubility: DMSO:79 mg/mL (234.16 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.93 mM)

Bioactivity

• Target IC50:
  ERG (human):> 10 μM
• In Vivo:
  METHODS: To assess the activity and efficacy of Voxelotor, Voxelotor (100-150 mg/kg, 0.5% methylcellulose/0.5% SDS) was administered by gavage to a mouse model of SCD twice daily for 9-12 days. RESULTS: Voxelotor reduced isolated sickle cells and prolonged erythrocyte half-life in the SCD mouse model.
• In Vitro:
  METHODS: Voxelotor (3-30 µmol/L) was incubated with hemoglobin (25 µmol/L) in TES or saline buffer at 37 ℃ for 45 min, and changes in the binding affinity of O2 for Hb were measured using a TCS hematology analyzer. RESULTS: Voxelotor, a small molecule that binds to the N-terminal α-chain of Hb, increases the affinity of HbS for oxygen, delays HbS polymerization in vitro and prevents erythrocyte sickling. METHODS: HepG2 cells were treated with Voxelotor (1 µg/mL) and their metabolites were analyzed by liquid chromatography, high-resolution MS and tandem MS. RESULTS: Voxelotor can be used for the identification of phase I and phase II metabolites in vitro.

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

polymerization, inhibit, GBT 440, GBT440, GBT-440, Inhibitor, HbS, haemoglobin, disease, cell, sickle, sickle hemoglobin (HbS), SCD, voxelotor

Compound Identifiers

PubChem CID

71602803