This product is for research use only, not for human use. We do not sell to patients.
| Size | Price | Stock |
|---|---|---|
| 5mg | $70 | 3-6 Days |
| 10mg | $100 | 3-6 Days |
| 25mg | $150 | 3-6 Days |
| 50mg | $250 | 3-6 Days |
| 100mg | $430 | 3-6 Days |
| 250mg | $700 | 3-6 Days |
| 500mg | $1250 | 3-6 Days |
: Cat #: V2795 CAS #: 1446321-46-5 Purity ≥ 98%
Description: Voxelotor (formerly known as GBT-440; trade name: Oxbryta) is a potent and orally bioactive allosteric effector of sickle cell hemoglobin. It increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, Voxelotor binds with a 1:1 stoichiometry. Voxelotor is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of ∼150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. In November 2019, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease (SCD) for those 12 years of age and older. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.
Publications Citing InvivoChem Products
Product Promise
- Physicochemical and Storage Information
- Protocol
- Related Biological Data
- Stock Solution Preparation
- Quality Control Documentation
| Molecular Weight (MW) | 337.37 |
|---|---|
| Molecular Formula | C19H19N3O3 |
| CAS No. | 1446321-46-5 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility In Vitro | DMSO: 67 mg/mL (198.59 mM) |
| Water: <1 mg/mL | |
| Ethanol:67 mg/mL (198.59 mM) | |
| Solubility In Vivo | O=CC1=C(OCC2=CC=CN=C2C3=CC=NN3C(C)C)C=CC=C1O |
| Synonyms | GBT-440, GBT 440, GBT440; GTx-011, GTx011, GTx 011; Voxelotor; Oxbryta |
| Protocol | In Vitro | In vitro activity: GBT440 binds to the N-terminal a chain of Hb. it is a new potent allosteric effector of sickle cell hemoglobin that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. GBT440 inhibits these isozymes(CYP 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4) with IC50 ranging from 7.9 to 148 μM. It is not a substrate for either P-gp or BCRP transporters. Kinase Assay: Voxelotor (formerly known as GBT-440) is a potent and orally active allosteric effector of sickle cell hemoglobin. It increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, Voxelotor binds with a 1:1 stoichiometry. Cell Assay: whole blood (20% Hct) from SCD patients who has been transfusion free for 2 to 3 months (HbS > 70%) is incubated with various concentrations of GBT440 for 1 h at 37°C, diluted 100-fold in TES/saline buffer and deoxygenated in a Hemox Analyser. |
|---|---|---|
| In Vivo | BT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. In a murine model of SCD, GBT440 extends the half-life of RBCs, reduces reticulocyte counts and prevents ex vivo RBC sickling. Importantly, oral dosing of GBT440 in animals demonstrates suitability for once daily dosing in humans and a highly selective partitioning into RBCs, which is a key therapeutic safety attribute. GBT440 shows dose proportional PK, a terminal half-life of 1.5-3 d. GBT440 has favorable oral bioavailability of 60, 37, and 36% in rats, dogs, and monkeys, respectively, with similar blood and plasma half-lives of approximately 20 h each. T1/2 value of GBT440 in all animal species is significantly shorter than the T1/2 of red blood cells (∼20 days), which supports that binding of GBT440 to hemoglobin is a reversible process. GBT440 is currently in Phase 3 clinical trials (NCT03036813) in SCD patients. | |
| Animal model | Sprague-Dawley rats |
| Solvent volume to be added | Mass (the weight of a compound) | |||
|---|---|---|---|---|
| Mother liquor concentration | 1mg | 5mg | 10mg | 20mg |
| 1mM | 2.9641 mL | 14.8205 mL | 29.6410 mL | 59.2821 mL |
| 5mM | 0.5928 mL | 2.9641 mL | 5.9282 mL | 11.8564 mL |
| 10mM | 0.2964 mL | 1.4821 mL | 2.9641 mL | 5.9282 mL |
| 20mM | 0.1482 mL | 0.7410 mL | 1.4821 mL | 2.9641 mL |
This equation is commonly abbreviated as: C1 V1 = C2 V2
- (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
- (2) Be sure to add the solvent(s) in order.