Voxelotor

Catalog No.S8540 Batch:S854003

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Technical Data

Formula

C19H19N3O3
Molecular Weight 337.37 CAS No. 1446321-46-5
Solubility (25°C)* In vitro DMSO 67 mg/mL (198.59 mM)
Ethanol 5 mg/mL (14.82 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Voxelotor is a novel small molecule hemoglobin modifier which increases hemoglobin oxygen affinity.
In vitro GBT440 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[1]. It binds to the N-terminal a chain of Hb[2].
In vivo 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[1]. GBT440 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[2].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    sickle RBCs

  • Concentrations

    0, 300, 600, 1000 μM

  • Incubation Time

    1 h

  • Method

    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
Animal Study:

[1]
  • Animal Models

    Sprague-Dawley rats

  • Dosages

    7.2 to 120 mg/kg

  • Administration

    oral administration

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.