selumetinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
MEK (MAPK kinase) tyrosine kinase inhibitors 5388 606143-52-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • selumetinib
  • selumetinib sulfate
  • koselugo
  • AZD6244
  • ARRY-142886
Selumetinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers
  • Molecular weight: 457.68
  • Formula: C17H15BrClFN4O3
  • CLOGP: 3.73
  • LIPINSKI: 0
  • HAC: 7
  • HDO: 3
  • TPSA: 88.41
  • ALOGS: -4.34
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
S (Water solubility) 0.15 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ

Approvals:

DateAgencyCompanyOrphan
June 17, 2021 EMA ASTRAZENECA AB
April 10, 2020 FDA ASTRAZENECA LP
Sept. 26, 2022 PMDA ALEXION PHARMA GK

FDA Adverse Event Reporting System (Female)

None

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
Blood creatine phosphokinase increased 75.56 57.58 21 156 44836 34911918
Paronychia 66.98 57.58 12 165 3393 34953361

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
Blood creatine phosphokinase increased 107.90 38.66 29 300 66061 79677998
Paronychia 102.81 38.66 19 310 7789 79736270
Dermatitis acneiform 50.68 38.66 11 318 9982 79734077

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EE04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Mitogen-activated protein kinase (MEK) inhibitors
FDA EPC N0000175605 Kinase Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:79091 MEK inhibitor
CHEBI has role CHEBI:149553 anticoronaviral drug
FDA MoA N0000193943 Mitogen-Activated Protein Kinase Kinase 1 Inhibitors
FDA MoA N0000193944 Mitogen-Activated Protein Kinase Kinase 2 Inhibitors

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

DiseaseRelationSNOMED_IDDOID
Neurofibromatosis type 1 indication 92824003 DOID:0111253
Plexiform neurofibroma indication 403818001 DOID:5151




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.84 acidic
pKa2 3.24 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 10MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL 9562017 Dec. 12, 2026 TREATMENT OF PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
EQ 25MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL 9562017 Dec. 12, 2026 TREATMENT OF PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 10MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL April 10, 2025 NEW CHEMICAL ENTITY
EQ 25MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL April 10, 2025 NEW CHEMICAL ENTITY
EQ 10MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL April 10, 2027 INDICATED FOR THE TREATMENT OF PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
EQ 25MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL April 10, 2027 INDICATED FOR THE TREATMENT OF PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Dual specificity mitogen-activated protein kinase kinase 1 Kinase INHIBITOR IC50 7.85 SCIENTIFIC LITERATURE DRUG LABEL
Dual specificity mitogen-activated protein kinase kinase 2 Kinase INHIBITOR IC50 7.85 SCIENTIFIC LITERATURE DRUG LABEL
BMP-2-inducible protein kinase Kinase Kd 5.79 CHEMBL
Casein kinase II subunit alpha' Kinase Kd 5.55 CHEMBL
Epidermal growth factor receptor Kinase Kd 5.66 CHEMBL
Structural maintenance of chromosomes protein 1A Unclassified Kd 6.44 CHEMBL
Uncharacterized protein FLJ45252 Unclassified Kd 6.09 CHEMBL
Structural maintenance of chromosomes protein 2 Unclassified Kd 6.68 CHEMBL
AP2-associated protein kinase 1 Kinase Kd 5.89 CHEMBL

External reference:

IDSource
6UH91I579U UNII
943332-08-9 SECONDARY_CAS_RN
C2980074 UMLSCUI
CHEBI:90227 CHEBI
3EW PDB_CHEM_ID
CHEMBL1614701 ChEMBL_ID
10127622 PUBCHEM_CID
DB11689 DRUGBANK_ID
CHEMBL2105684 ChEMBL_ID
9078 INN_ID
D10024 KEGG_DRUG
5665 IUPHAR_LIGAND_ID
018323 NDDF
018324 NDDF
1217205000 SNOMEDCT_US
870689004 SNOMEDCT_US
870753001 SNOMEDCT_US
4039314 VANDF
2289380 RXNORM
332908 MMSL
38304 MMSL
d09410 MMSL
C517975 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0610 CAPSULE 10 mg ORAL NDA 28 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0625 CAPSULE 25 mg ORAL NDA 28 sections