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Details

Stereochemistry ACHIRAL
Molecular Formula C19H19N3O3
Molecular Weight 337.3725
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VOXELOTOR

SMILES

CC(C)N1N=CC=C1C2=NC=CC=C2COC3=C(C=O)C(O)=CC=C3

InChI

InChIKey=FWCVZAQENIZVMY-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C19H19N3O3
Molecular Weight 337.3725
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

GBT440 (previously GTx011) is a potent and direct drug for sickle cell treatment. In sickle cell anemia, abnormal hemoglobin molecules are formed, which causes problems for the flow of blood and oxygen through the body. GBT440 can selectively bind to hemoglobin, thereby increasing its affinity for oxygen. By inhibiting hemoglobin polymerization, it also prevents deformation of the red blood cells. GBT440, renamed Voxelotor, is thought to help prevent sickle cells blocking blood vessels, and therefore reduces pain (sickle cell crisis) experienced by patients. GBT440 is well absorbed following intravenous and oral administration, and quickly partitions into the red blood cell with a small part re‐distributed into the plasma. GBT440 was well tolerated in a randomized, placebo‐controlled, double blind, parallel group phase I/II study in healthy volunteers and sickle cell disease patients. Headache is the most reported adverse event related to the use of this drug, and no serious adverse events are known. A phase 3 clinical trial examining the efficacy and safety of the drug (compared to placebo) is planned to be completed in 2019. Voxelotor was also studied as a potential therapy for treatment of low oxygen levels in the blood of idiopathic pulmonary fibrosis patients, but this program was discontinued because of a lack of clinical benefits.

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Cmax

ValueDoseCo-administeredAnalytePopulation
2.21 μg/mL
1000 mg single, oral
VOXELOTOR plasma
Homo sapiens
146 μg/mL
1000 mg single, oral
VOXELOTOR red blood cells
Homo sapiens
136 μg/mL
1000 mg single, oral
VOXELOTOR red blood cells
Homo sapiens
11.4 μg/mL
900 mg 1 times / day steady-state, oral
VOXELOTOR plasma
Homo sapiens
2.91 μg/mL
300 mg 1 times / day steady-state, oral
VOXELOTOR plasma
Homo sapiens
2.94 μg/mL
1000 mg single, oral
VOXELOTOR plasma
Homo sapiens
688 μg/mL
900 mg 1 times / day steady-state, oral
VOXELOTOR red blood cells
Homo sapiens
225 μg/mL
300 mg 1 times / day steady-state, oral
VOXELOTOR red blood cells
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
166 μg × h/mL
1000 mg single, oral
VOXELOTOR plasma
Homo sapiens
10000 μg × h/mL
1000 mg single, oral
VOXELOTOR red blood cells
Homo sapiens
15800 μg × h/mL
1000 mg single, oral
VOXELOTOR red blood cells
Homo sapiens
215 μg × h/mL
900 mg 1 times / day steady-state, oral
VOXELOTOR plasma
Homo sapiens
56.6 μg × h/mL
300 mg 1 times / day steady-state, oral
VOXELOTOR plasma
Homo sapiens
134 μg × h/mL
1000 mg single, oral
VOXELOTOR plasma
Homo sapiens
14000 μg × h/mL
900 mg 1 times / day steady-state, oral
VOXELOTOR red blood cells
Homo sapiens
4950 μg × h/mL
300 mg 1 times / day steady-state, oral
VOXELOTOR red blood cells
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
49.7 h
1000 mg single, oral
VOXELOTOR red blood cells
Homo sapiens
61.1 h
1000 mg single, oral
VOXELOTOR red blood cells
Homo sapiens
85.1 h
900 mg 1 times / day steady-state, oral
VOXELOTOR red blood cells
Homo sapiens
80.3 h
300 mg 1 times / day steady-state, oral
VOXELOTOR red blood cells
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

Substance Class Chemical
Record UNII
3ZO554A4Q8
Record Status Validated (UNII)
Record Version