General Information of Drug (ID: DMCS6M5)

Drug Name
Voxelotor
Synonyms
Hemoglobin Modulators-1; 1446321-46-5; UNII-3ZO554A4Q8; GBT 440; 3ZO554A4Q8; 2-hydroxy-6-([2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl]methoxy)benzaldehyde; 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde; 2-hydroxy-6-((2-(1-(propan-2-yl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde; Voxelotor [USAN]; SCHEMBL15065529; Voxelotor(GBT440, GTx011); GTX-011; GBT-440; MolPort-044-830-677; FWCVZAQENIZVMY-UHFFFAOYSA-N; AKOS030526545; ZINC145969085; CS-5317; HY-18681; DA-44587; S
Indication
Disease Entry ICD 11 Status REF
Sickle-cell disorder 3A51 Approved [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 337.4
Logarithm of the Partition Coefficient (xlogp) 2.7
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2 h [2]
Clearance
The apparent oral clearance of drug is 6.7 L/h [3]
Elimination
62.6% of the voxelotor dose administered orally as well as its metabolites are found in the feces (with 33.3% as unchanged drug) and 35.5% in urine (with only 0.08% unchanged drug) [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 35.5 hours [3]
Vd
The volume of distribution (Vd) of drug is 338 L [3]
Chemical Identifiers
Formula
C19H19N3O3
IUPAC Name
2-hydroxy-6-[[2-(2-propan-2-ylpyrazol-3-yl)pyridin-3-yl]methoxy]benzaldehyde
Canonical SMILES
CC(C)N1C(=CC=N1)C2=C(C=CC=N2)COC3=CC=CC(=C3C=O)O
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
Cross-matching ID
PubChem CID
71602803
CAS Number
1446321-46-5
DrugBank ID
DB14975
TTD ID
D09RII
INTEDE ID
DR1713
ACDINA ID
D01530
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Hemoglobin (HB) TTQO71U HBA_HUMAN Modulator [1]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [4]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [4]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Protein Interaction/Cellular Processes [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Voxelotor (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Avapritinib DMK2GZX Major Decreased metabolism of Voxelotor caused by Avapritinib mediated inhibition of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [6]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Voxelotor caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [7]
Pemigatinib DM819JF Moderate Decreased metabolism of Voxelotor caused by Pemigatinib mediated inhibition of CYP450 enzyme. Liver cancer [2C12] [8]
Pralsetinib DMWU0I2 Moderate Decreased metabolism of Voxelotor caused by Pralsetinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [9]
Selpercatinib DMZR15V Major Decreased metabolism of Voxelotor caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [10]
Ubrogepant DM749I3 Moderate Decreased metabolism of Voxelotor caused by Ubrogepant mediated inhibition of CYP450 enzyme. Migraine [8A80] [11]
Upadacitinib DM32B5U Moderate Decreased metabolism of Voxelotor caused by Upadacitinib mediated inhibition of CYP450 enzyme. Rheumatoid arthritis [FA20] [12]
⏷ Show the Full List of 7 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Carmellose sodium E00625 Not Available Disintegrant
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol E00666 Not Available Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Colcothar yellow E00436 518696 Colorant
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 10 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Voxelotor 500 mg tablet 500 mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
2 Hutchaleelaha A, Patel M, Washington C, Siu V, Allen E, Oksenberg D, Gretler DD, Mant T, Lehrer-Graiwer J: Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. Br J Clin Pharmacol. 2019 Jun;85(6):1290-1302. doi: 10.1111/bcp.13896. Epub 2019 Mar 31.
3 FDA Approved Drug Products: Oxbryta (voxelotor) tablets
4 FDA label of Fedratinib. The 2020 official website of the U.S. Food and Drug Administration.
5 Voxelotor for the treatment of sickle cell disease. Expert Rev Hematol. 2021 Mar;14(3):253-262. doi: 10.1080/17474086.2021.1893688. Epub 2021 Mar 4.
6 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
7 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
8 Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
9 Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
10 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
11 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
12 Product Information. Rinvoq (upadacitinib). AbbVie US LLC, North Chicago, IL.