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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.629 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 6.730 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 45.394 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 4.315 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 3.680 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 8.540 % High 1
herg hERG pIC50 4.605 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 3.304 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 9.484 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 2.640 % High 1
kinase-safety-class ABL1,ABL2,ACVR2B,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK14,CDK16,CDK19,CDK2,CDK4,CDK5,CDK6,CDK7,CDK9,CLK4,CSF1R,DDR1,DYRK1B,EGFR,EPHA2,EPHB1,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FYN,GAK,GRK2,GSK3B,IRAK1,IRAK3,ITK,JAK1,JAK2,KDR,KIT,LCK,LYN,MAP2K1,MAP2K6,MAP3K10,MAP3K11,MAP3K14,MAP3K21,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK11,MAPK14,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,NTRK1,PDGFRB,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKCD,PRKDC,RET,SIK2,SIK3,SRC,STK33,SYK,TEK,TGFBR1,TTK,TYRO3,ULK1,ULK2,YES1 94
kinase-selectivity-class ACVR2B,AURKA,AXL,BRAF,CAMK2D,CDK9,CSF1R,DDR1,DYRK1B,EPHB4,GRK2,JAK1,LCK,LYN,MAP2K1,MAP3K21,MAP4K1,MAP4K3,MAPK1,MAPK7,MARK4,PRKCD,SIK2,SIK3,STK33,SYK,ULK1 27
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 36.813 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 31.550 High 1
mh-clint Mouse hepatocyte intrinsic clearance 29.785 High 1
mppb Mouse plasma protein binding (% unbound) 3.840 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 45.709 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 6.460 % High 1
rat-kpuu-brain Rat brain Kpuu 0.017 % High 1
rh-clint Rat hepatocyte intrinsic clearance 10.209 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 34.570 % High 1
rppb Rat plasma protein binding (% unbound) 2.800 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 10.209 uM High 1

Approvals:

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

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
Blood creatine phosphokinase increased 169.94 42.74 40 543 33983 90593881
Paronychia 124.01 42.74 24 559 7982 90619882
Dermatitis acneiform 116.80 42.74 22 561 6332 90621532
Neurofibrosarcoma 79.67 42.74 10 573 190 90627674
Acne 60.43 42.74 17 566 28490 90599374

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
Paronychia 201.04 50.20 37 578 4218 42616502
Blood creatine phosphokinase increased 166.35 50.20 50 565 48288 42572432
Dermatitis acneiform 100.08 50.20 23 592 7716 42613004
Neurofibrosarcoma 65.66 50.20 8 607 48 42620672
Retinal detachment 51.29 50.20 13 602 6512 42614208

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 258.88 42.22 70 939 73007 110515283
Paronychia 249.07 42.22 48 961 11033 110577257
Dermatitis acneiform 177.16 42.22 37 972 12658 110575632
Acne 90.15 42.22 26 983 33494 110554796
Neurofibrosarcoma 73.21 42.22 10 999 258 110588032

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
FDA MoA N0000193943 Mitogen-Activated Protein Kinase Kinase 1 Inhibitors
FDA MoA N0000193944 Mitogen-Activated Protein Kinase Kinase 2 Inhibitors
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:79091 EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
CHEBI has role CHEBI:149553 anticoronaviral agent

Related Drugs by ATC class:

L01EE Mitogen-activated protein kinase (MEK) inhibitors 4 drugs
binimetinibcobimetinibmirdametinibtrametinib

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 ADULT AND PEDIATRIC PATIENTS 1 YEAR 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 ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
EQ 5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL 9562017 Dec. 12, 2026 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
EQ 7.5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL 9562017 Dec. 12, 2026 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 1 YEAR OF AGE AND OLDER WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
EQ 10MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL 12364684 March 26, 2029 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 1 YEAR 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 12364684 March 26, 2029 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 1 YEAR 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, 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)
EQ 5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL April 10, 2027 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)
EQ 7.5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL April 10, 2027 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)
EQ 10MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL Sept. 10, 2028 NEW PATIENT POPULATION
EQ 25MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL Sept. 10, 2028 NEW PATIENT POPULATION
EQ 5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL Sept. 10, 2028 NEW PRODUCT
EQ 7.5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL Sept. 10, 2028 NEW PRODUCT
EQ 10MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL Nov. 19, 2028 NEW PATIENT POPULATION
EQ 25MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL Nov. 19, 2028 NEW PATIENT POPULATION
EQ 5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL Nov. 19, 2028 NEW PATIENT POPULATION
EQ 7.5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL Nov. 19, 2028 NEW PATIENT POPULATION
EQ 10MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL Nov. 19, 2032 TREATMENT OF ADULT PATIENTS WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
EQ 25MG BASE KOSELUGO ASTRAZENECA N213756 April 10, 2020 RX CAPSULE ORAL Nov. 19, 2032 TREATMENT OF ADULT PATIENTS WITH NEUROFIBROMATOSIS TYPE 1 (NF1) WHO HAVE SYMPTOMATIC, INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
EQ 5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL Nov. 19, 2032 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)
EQ 7.5MG BASE KOSELUGO ASTRAZENECA N219943 Sept. 10, 2025 RX GRANULE ORAL Nov. 19, 2032 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)

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 Structural Kd 6.44 CHEMBL
Uncharacterized protein FLJ45252 Unclassified Kd 6.09 CHEMBL
Structural maintenance of chromosomes protein 2 Structural 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
4039314 VANDF
C2980074 UMLSCUI
CHEBI:90227 CHEBI
3EW PDB_CHEM_ID
CHEMBL1614701 ChEMBL_ID
10127622 PUBCHEM_CID
DB11689 DRUGBANK_ID
CHEMBL2105684 ChEMBL_ID
9078 INN_ID
C517975 MESH_SUPPLEMENTAL_RECORD_UI
D10024 KEGG_DRUG
5665 IUPHAR_LIGAND_ID
1217205000 SNOMEDCT_US
870689004 SNOMEDCT_US
870753001 SNOMEDCT_US
332908 MMSL
38304 MMSL
d09410 MMSL
018323 NDDF
018324 NDDF
2289380 RXNORM
6UH91I579U INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0610 CAPSULE 10 mg ORAL NDA 30 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0610 CAPSULE 10 mg ORAL NDA 30 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0625 CAPSULE 25 mg ORAL NDA 30 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0625 CAPSULE 25 mg ORAL NDA 30 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0635 GRANULE 5 mg ORAL NDA 30 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0635 GRANULE 5 mg ORAL NDA 30 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0640 GRANULE 7.50 mg ORAL NDA 30 sections
KOSELUGO HUMAN PRESCRIPTION DRUG LABEL 1 0310-0640 GRANULE 7.50 mg ORAL NDA 30 sections