ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors Voxelotor

Voxelotor

Product NameVoxelotor
CAS1446321-46-5
MFC19H19N3O3
MW337.37
EINECS
MOL File1446321-46-5.mol

Chemical Properties

Melting point	95 - 97oC
Boiling point	539.2±50.0 °C(Predicted)
Density	1.23±0.1 g/cm3(Predicted)
storage temp.	-20°C Freezer, Under inert atmosphere
solubility	Chloroform (Slightly), DMSO (Slightly)
form	Solid
pka	7.67±0.10(Predicted)
color	White to Off-White
InChI	InChI=1S/C19H19N3O3/c1-13(2)22-16(8-10-21-22)19-14(5-4-9-20-19)12-25-18-7-3-6-17(24)15(18)11-23/h3-11,13,24H,12H2,1-2H3
InChIKey	FWCVZAQENIZVMY-UHFFFAOYSA-N
SMILES	C(=O)C1=C(OCC2=CC=CN=C2C2N(C(C)C)N=CC=2)C=CC=C1O

Usage And Synthesis

Uses

GBT 440 is a potent allosteric effector of sickle cell hemoglobin (Hb) that increases the affinity of Hb for oxygen and inhibits its polymerization when subjected to hypoxic conditions.

Biological Activity

Voxelotor improves the abnormal aggregation of hemoglobin under hypoxic conditions, which is the main cause of sickle cell disease-related red blood cell dysfunction, by forming a Schiff base with the N-terminal valine of the hemoglobin alpha chain, increasing the affinity of sickle cell hemoglobin for oxygen and preventing its aggregation.

Synthesis

below shows the synthesis route of Voxelotor

in vivo

Animal Model:	HbSS Townes knock-in sickle mice (SS mice)^[1]
Dosage:	100 and 150 mg/kg
Administration:	Oral administration; twice a day; for 9-12 days
Result:	Reduced haemolysis.

Animal Model:	C57BL/6J mice, Sprague-Dawley rats, Beagle dogs and Cynomolgus monkeys^[1]
Dosage:	70, 1.6, 1 and 1 mg/kg for mice, rats, dogs and monkeys, respectively 30, 7.2, 2.5 and 4.25 mg/kg for mice, rats, dogs and monkeys, respectively
Administration:	Intravenous (IV: 70, 1 6, 1 and 1 mg/kg, respectively) Oral (PO: 30, 7 2, 2 5 and 4 3 mg/kg, respectively)
Result:	T_1/2s of 11.7, 19.1±1.5, 66.0±11, 28.8±4.0 hours for mouse (70 mg/kg; i.v.), rat (1.6 mg/kg; i.v.), dog (1 mg/kg; i.v.), and momkey (1 mg/kg; i.v.), respectively. C_maxs of 81.9, 71.2±6.0, 5.56±1.6, and 25.2±5.5 μg/mL for mouse (30 mg/kg; p.o.), rat (7.2 mg/kg; p.o.), dog (2.5 mg/kg; p.o.), and momkey (4.25 mg/kg; p.o.), respectively.

References

[1] Patent: WO2013/102142, 2013, A1. Location in patent: Paragraph 0179
[2] Patent: WO2013/102142, 2013, A1. Location in patent: Paragraph 0178

Voxelotor

Chemical Properties

Usage And Synthesis

Preparation Products And Raw materials

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