Voxelotor (GBT 440) is a first-in-class, potent polymeric inhibitor of sickle hemoglobin (HbS). Voxelotor (GBT440) is first-in-class hemoglobin oxygen-affinity modulator. Voxelotor (GBT440) binds to the N-terminal a chain of haemoglobin (Hb), increases haemoglobin S (HbS) affinity for oxygen, delays in vitro HbS polymerization and prevents sickling of red blood cells (RBCs). Voxelotor has the potential to be used in sickle cell anaemia research.
In vivo, Voxelotor (GBT440; 100-150 mg/kg; administered twice a day by oral gavage for 9-12 days) reduces ex vivo sickling and prolongs red blood cells (RBCs) half-life in a murine model of sickle cell disease (SCD).
Molecular Weight | 337.37 |
Formula | C19H19N3O3 |
CAS Number | 1446321-46-5 |
Solubility (25°C) | DMSO ≥ 90 mg/mL |
Storage | 2-8°C, dry, sealed |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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