elexacaftor Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
cystic fibrosis transmembrane regulator (CFTR) protein modulators 5372 2216712-66-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • elexacaftor
Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity as measured by CFTR mediated chloride transport.
  • Molecular weight: 597.66
  • Formula: C26H34F3N7O4S
  • CLOGP: 4.43
  • LIPINSKI: 2
  • HAC: 11
  • HDO: 1
  • TPSA: 124.24
  • ALOGS: -4.49
  • ROTB: 8

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 21, 2020 EMA Vertex Pharmaceuticals (Ireland) Limited
Oct. 10, 2019 FDA VERTEX PHARMS INC

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
Infective pulmonary exacerbation of cystic fibrosis 464.51 40.72 114 3042 10693 46672213
Productive cough 218.66 40.72 93 3063 50622 46632284
Headache 139.10 40.72 165 2991 478187 46204719
Cough 116.19 40.72 107 3049 230142 46452764
Abdominal pain upper 111.34 40.72 86 3070 145219 46537687
Hospitalisation 84.97 40.72 53 3103 63332 46619574
Influenza 84.31 40.72 60 3096 89210 46593696
Rash 71.71 40.72 103 3053 356409 46326497
Haemoptysis 71.39 40.72 35 3121 26154 46656752
Cystic fibrosis 59.33 40.72 18 3138 3670 46679236
Sputum increased 57.74 40.72 15 3141 1741 46681165
Weight increased 54.35 40.72 61 3095 164412 46518494
Paranasal sinus hypersecretion 53.00 40.72 16 3140 3208 46679698
Exposure during pregnancy 46.13 40.72 46 3110 108166 46574740
Distal intestinal obstruction syndrome 43.38 40.72 9 3147 388 46682518

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
Infective pulmonary exacerbation of cystic fibrosis 332.51 51.27 84 2034 8488 29941872
Productive cough 259.01 51.27 92 2026 29861 29920499
Headache 143.20 51.27 111 2007 182195 29768165
Abdominal pain upper 131.57 51.27 71 2047 62480 29887880
Cough 103.69 51.27 79 2039 125563 29824797
Influenza 73.97 51.27 43 2075 43355 29907005
Sputum increased 70.78 51.27 18 2100 1839 29948521
Testicular pain 68.19 51.27 19 2099 2753 29947607
Weight increased 54.80 51.27 44 2074 74869 29875491
Paranasal sinus hypersecretion 52.50 51.27 12 2106 780 29949580

Pharmacologic Action:

SourceCodeDescription
ATC R07AX32 RESPIRATORY SYSTEM
OTHER RESPIRATORY SYSTEM PRODUCTS
OTHER RESPIRATORY SYSTEM PRODUCTS
Other respiratory system products
MeSH PA D065101 Chloride Channel Agonists
MeSH PA D049990 Membrane Transport Modulators

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Cystic fibrosis indication 190905008 DOID:1485

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.64 acidic
pKa2 1.88 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG,75MG,50MG;N/A,150MG,N/A TRIKAFTA (COPACKAGED) VERTEX PHARMS INC N212273 Oct. 21, 2019 RX TABLET, TABLET ORAL Feb. 12, 2023 NEW CHEMICAL ENTITY
100MG,75MG,50MG;N/A,150MG,N/A TRIKAFTA (COPACKAGED) VERTEX PHARMS INC N212273 Oct. 21, 2019 RX TABLET, TABLET ORAL Oct. 21, 2024 NEW CHEMICAL ENTITY
100MG,75MG,50MG;N/A,150MG,N/A TRIKAFTA (COPACKAGED) VERTEX PHARMS INC N212273 Oct. 21, 2019 RX TABLET, TABLET ORAL Oct. 21, 2026 INDICATED FOR THE TREATMENT OF CYSTIC FIBROSIS (CF) IN PATIENTS AGED 12 YEARS AND OLDER WHO HAVE AT LEAST ONE F508DEL MUTATION IN THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE
100MG,75MG,50MG;N/A,150MG,N/A TRIKAFTA (COPACKAGED) VERTEX PHARMS INC N212273 Oct. 21, 2019 RX TABLET, TABLET ORAL Dec. 21, 2027 TREATMENT OF CYSTIC FIBROSIS (CF) IN PATIENTS AGED 12 YEARS AND OLDER WHO HAVE A MUTATION IN THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE THAT IS RESPONSIVE BASED ON IN VITRO DATA

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cystic fibrosis transmembrane conductance regulator Ion channel UNKNOWN DRUG LABEL

External reference:

IDSource
4038884 VANDF
C5139717 UMLSCUI
CHEMBL4298128 ChEMBL_ID
DB15444 DRUGBANK_ID
D11700 KEGG_DRUG
C000629074 MESH_SUPPLEMENTAL_RECORD_UI
134587348 PUBCHEM_CID
10552 IUPHAR_LIGAND_ID
11180 INN_ID
RRN67GMB0V UNII
2256951 RXNORM
37631 MMSL
d09420 MMSL
018170 NDDF
827070004 SNOMEDCT_US

Pharmaceutical products:

None