| Identification | Back Directory | [Name]
Voxelotor | [CAS]
1446321-46-5 | [Synonyms]
GTx011
GBT 440
Voxelotor
GBT-440(Voxelotor)
GTX011;GTX011;GTX011
Hemoglobin Modulators-1
Voxelotor(GBT440, GTX011)
Voxelotor, GBT-440, GBT 440, GBT440, GTx-011, GTx011, GTx 011
VOXELOTOR, GBT-440, GBT 440, GBT440, GTX-011, GTX011, GTX 011;
2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde
2-Hydroxy-6-{[2-(1-isopropyl-1H-pyrazol-5-yl)-3-pyridinyl]methoxy}benzaldehyde
2-hydroxy-6-([2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl]methoxy)benzaldehyde
Benzaldehyde, 2-hydroxy-6-[[2-[1-(1-methylethyl)-1H-pyrazol-5-yl]-3-pyridinyl]methoxy]- | [Molecular Formula]
C19H19N3O3 | [MDL Number]
MFCD29053764 | [MOL File]
1446321-46-5.mol | [Molecular Weight]
337.37 |
| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [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]
Voxelotor (GBT440；100-150 mg/kg；通过口服强饲法每天给药两次，持续 9-12 天) 在镰状细胞病 (SCD) 小鼠模型中减少离体镰状细胞并延长红细胞 (RBC) 的半衰期[1]。
Voxelotor 显示小鼠的 T1/2 为 11.7、19.1±1.5、66.0±11、28.8±4.0 小时 (70 mg/kg；iv)，大鼠 (1.6 mg/kg；iv)，狗 (1 mg/kg；iv)，和 momkey (1 mg/kg；iv)，分别[1]。
Voxelotor 对小鼠 (30 mg/kg；po)、大鼠 (7.2 mg/kg；po)、狗 (2.5 mg/kg；po) 和 momkey (4.25 mg/kg；po) Cmaxs 为 81.9, 71.2±6.0, 5.56±1.6, and 25.2±5.5 μg/mL[1]。 | 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: | T1/2s 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.
Cmaxs 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 |
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