voxelotor 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
5356 1446321-46-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • voxelotor
  • GBT440
  • oxbryta
  • GTX-011
Voxelotor is a hemoglobin S (HbS) polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to red blood cells (RBCs). By increasing the affinity of Hb for oxygen, voxelotor demonstrates dose-dependent inhibition of HbS polymerization. Nonclinical studies suggest that voxelotor may inhibit RBC sickling, improve RBC deformability, and reduce whole blood viscosity.
  • Molecular weight: 337.38
  • Formula: C19H19N3O3
  • CLOGP: 3.29
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 1
  • TPSA: 77.24
  • ALOGS: -3.81
  • ROTB: 6
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
S (Water solubility) 0.03 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2D,CDK9,EIF2AK3,ERBB2,GRK2,ITK,MAPK7,PDK1,PDK2,PDK4,PIK3CG,PRKDC 15
kinase-selectivity-class ACVR2B,AXL,BRAF,CDK9,GRK2,MAP2K6 6
pfas-class PFAS structural alert (1 = True, 0 = False) 0

Approvals:

DateAgencyCompanyOrphan
Nov. 25, 2019 FDA GLOBAL BLOOD THERAPEUTICS INC
Feb. 14, 2022 EMA GLOBAL BLOOD THERAPEUTICS NETHERLANDS B. V.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Sickle cell anaemia with crisis 4496.06 62.63 636 2162 6661 90618988
Acute chest syndrome 538.94 62.63 80 2718 1068 90624581
Therapy interrupted 303.45 62.63 96 2702 50012 90575637
Therapy cessation 229.62 62.63 72 2726 36289 90589360
Hypersplenism 174.91 62.63 26 2772 347 90625302
Abdominal symptom 117.53 62.63 19 2779 449 90625200
Diarrhoea 103.70 62.63 135 2663 939055 89686594
Pain 98.94 62.63 136 2662 996205 89629444
Death 73.78 62.63 80 2718 456471 90169178
Hospitalisation 66.25 62.63 44 2754 128056 90497593
Osteonecrosis 65.11 62.63 26 2772 26215 90599434
Haemoglobin decreased 63.63 62.63 47 2751 161909 90463740

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Sickle cell anaemia with crisis 3785.89 83.24 557 1724 4333 42614721
Acute chest syndrome 763.12 83.24 115 2166 950 42618104
Therapy cessation 248.62 83.24 76 2205 20374 42598680
Therapy interrupted 238.12 83.24 75 2206 22175 42596879
Hypersplenism 228.13 83.24 37 2244 502 42618552
Abdominal symptom 183.18 83.24 31 2250 552 42618502
Pain 182.13 83.24 129 2152 244719 42374335
Osteonecrosis 163.40 83.24 52 2229 15813 42603241
Priapism 113.72 83.24 32 2249 6375 42612679
Cholelithiasis 86.51 83.24 36 2245 23310 42595744

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Sickle cell anaemia with crisis 6110.73 71.84 873 2968 8672 110576786
Acute chest syndrome 1237.96 71.84 181 3660 1922 110583536
Hypersplenism 419.27 71.84 62 3779 704 110584754
Abdominal symptom 321.62 71.84 50 3791 808 110584650
Pain 243.85 71.84 225 3616 954730 109630728
Osteonecrosis 242.99 71.84 76 3765 33665 110551793
Therapy interrupted 236.96 71.84 82 3759 49740 110535718
Therapy cessation 183.36 71.84 66 3775 44791 110540667
Cholelithiasis 114.93 71.84 52 3789 63370 110522088
Pulmonary hypertension 105.53 71.84 47 3794 55173 110530285
Death 97.26 71.84 120 3721 698749 109886709
Skin ulcer 72.46 71.84 38 3803 63607 110521851

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC B06AX03 BLOOD AND BLOOD FORMING ORGANS
OTHER HEMATOLOGICAL AGENTS
OTHER HEMATOLOGICAL AGENTS
Other hematological agents
MeSH PA D006401 Hematologic Agents
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA EPC N0000194027 Hemoglobin S Polymerization Inhibitor
FDA MoA N0000194028 Hemoglobin S Polymerization Inhibitors
CHEBI has role CHEBI:75835 anti-anaemic agent
CHEBI has role CHEBI:231911 renoprotective agent
CHEBI has role CHEBI:233423 antifibrotic agent

Related Drugs by ATC class:

B06AX Other hematological agents 2 drugs
crizanlizumabmitapivat

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Sickle cell disease indication 417357006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.15 acidic
pKa2 4.48 Basic
pKa3 2.17 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
300MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Oct. 14, 2022 DISCN TABLET ORAL 9248199 Jan. 29, 2034 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 1
300MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Oct. 14, 2022 DISCN TABLET ORAL 9248199 Jan. 29, 2034 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 2
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL 9248199 Jan. 29, 2034 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 1
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL 9248199 Jan. 29, 2034 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 2
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL 9248199 Jan. 29, 2034 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 1
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL 9248199 Jan. 29, 2034 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 2
300MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Oct. 14, 2022 DISCN TABLET ORAL 11452720 Feb. 6, 2035 TREATING SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR AND ANOTHER ACTIVE AGENT
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL 11452720 Feb. 6, 2035 TREATING SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR AND ANOTHER ACTIVE AGENT
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL 11452720 Feb. 6, 2035 TREATING SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR AND ANOTHER ACTIVE AGENT
300MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Oct. 14, 2022 DISCN TABLET ORAL 11020382 Dec. 2, 2036 INCREASING HEMOGLOBIN TO TREAT SICKLE CELL DISEASE BY ADMINISTERING 1500 MG OF VOXELOTOR ORALLY ONCE DAILY
300MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Oct. 14, 2022 DISCN TABLET ORAL 11020382 Dec. 2, 2036 TREATING SICKLE CELL DISEASE BY ADMINISTERING 1500 MG OF VOXELOTOR ORALLY ONCE DAILY
300MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Oct. 14, 2022 DISCN TABLET ORAL 11944612 Dec. 2, 2036 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 10
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL 11020382 Dec. 2, 2036 INCREASING HEMOGLOBIN TO TREAT SICKLE CELL DISEASE BY ADMINISTERING 1500 MG OF VOXELOTOR ORALLY ONCE DAILY
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL 11020382 Dec. 2, 2036 TREATING SICKLE CELL DISEASE BY ADMINISTERING 1500 MG OF VOXELOTOR ORALLY ONCE DAILY
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL 11944612 Dec. 2, 2036 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 10
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL 11020382 Dec. 2, 2036 INCREASING HEMOGLOBIN TO TREAT SICKLE CELL DISEASE BY ADMINISTERING 1500 MG OF VOXELOTOR ORALLY ONCE DAILY
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL 11020382 Dec. 2, 2036 TREATING SICKLE CELL DISEASE BY ADMINISTERING 1500 MG OF VOXELOTOR ORALLY ONCE DAILY
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL 11944612 Dec. 2, 2036 TREATMENT OF SICKLE CELL DISEASE BY ADMINISTERING VOXELOTOR, AS RECITED IN CLAIM 10

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL Nov. 25, 2026 INDICATED FOR THE TREATMENT OF SICKLE CELL DISEASE (SCD) IN ADULTS AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL Nov. 25, 2026 FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
300MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Oct. 14, 2022 DISCN TABLET ORAL Dec. 17, 2028 FOR TREATMENT OF SICKLE CELL DISEASE (SCD) IN PEDIATRIC PATIENTS 4 YEARS OF AGE TO LESS THAN 12 YEARS OF AGE
500MG OXBRYTA GLOBAL BLOOD THERAPS N213137 Nov. 25, 2019 DISCN TABLET ORAL Dec. 17, 2028 FOR TREATMENT OF SICKLE CELL DISEASE (SCD) IN PEDIATRIC PATIENTS 4 YEARS OF AGE TO LESS THAN 12 YEARS OF AGE
300MG OXBRYTA GLOBAL BLOOD THERAPS N216157 Dec. 17, 2021 DISCN TABLET, FOR SUSPENSION ORAL Dec. 17, 2028 FOR TREATMENT OF SICKLE CELL DISEASE (SCD) IN PEDIATRIC PATIENTS 4 YEARS OF AGE TO LESS THAN 12 YEARS OF AGE

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
hemoglobin subunit alpha Transporter INHIBITOR EC50 5.09 SCIENTIFIC LITERATURE DRUG LABEL
Cytochrome P450 3A4 Enzyme INHIBITOR IC50 4.90 IUPHAR
Cytochrome P450 2C8 Enzyme INHIBITOR IC50 5.10 IUPHAR
Cytochrome P450 2C9 Enzyme INHIBITOR IC50 5.07 IUPHAR

External reference:

IDSource
3ZO554A4Q8 UNII
4038992 VANDF
C4723629 UMLSCUI
CHEBI:756602 CHEBI
CHEMBL4101807 ChEMBL_ID
71602803 PUBCHEM_CID
DB14975 DRUGBANK_ID
D11330 KEGG_DRUG
10454 INN_ID
C000628792 MESH_SUPPLEMENTAL_RECORD_UI
10559 IUPHAR_LIGAND_ID
833284006 SNOMEDCT_US
833304007 SNOMEDCT_US
327648 MMSL
37796 MMSL
d09458 MMSL
018213 NDDF
2265678 RXNORM
3ZO554A4Q8 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
OXBRYTA HUMAN PRESCRIPTION DRUG LABEL 1 72786-101 TABLET, FILM COATED 500 mg ORAL NDA 30 sections
OXBRYTA HUMAN PRESCRIPTION DRUG LABEL 1 72786-102 TABLET, FILM COATED 300 mg ORAL NDA 30 sections
OXBRYTA HUMAN PRESCRIPTION DRUG LABEL 1 72786-111 TABLET, FOR SUSPENSION 300 mg ORAL NDA 30 sections