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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5471 1847461-43-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • mobocertinib
  • mobocertinib succinate
  • exkivity
  • TAK-788
  • AP32788
Mobocertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that irreversibly binds to and inhibits EGFR exon 20 insertion mutations at lower concentrations than wild type (WT) EGFR. Two pharmacologically-active metabolites (AP32960 and AP32914) with similar inhibitory profiles to mobocertinib have been identified in the plasma after oral administration of mobocertinib. In vitro, mobocertinib also inhibited the activity of other EGFR family members (HER2 and HER4) and one additional kinase (BLK) at clinically relevant concentrations (IC50 values <2 nM).
  • Molecular weight: 585.71
  • Formula: C32H39N7O4
  • CLOGP: 5.48
  • LIPINSKI: 3
  • HAC: 11
  • HDO: 2
  • TPSA: 113.85
  • ALOGS: -4.63
  • ROTB: 13
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.456 High 0.89
caco2-efflux Caco-2 efflux ratio (BA/AB) 6.950 High 0.89
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 9.290 10^-6 cm/s High 0.89
dh-clint Dog hepatocyte intrinsic clearance 7.889 uL/min/10^6 cells High 0.89
dppb Dog plasma protein binding (% unbound) 1.140 % High 0.89
fcs-ppb Fetal calf serum protein binding (% unbound) 5.810 % High 0.89
herg hERG pIC50 5.378 pIC50 High 0.89
hh-clint Human hepatocyte intrinsic clearance 9.078 uL/min/10^6 cells High 0.89
hlm-clint Human liver microsomal intrinsic clearance 48.417 uL/min/mg protein High 0.89
hppb Human plasma protein binding (% unbound) 1.190 % High 0.89
kinase-safety-class AAK1,ACVR2B,ALK,AURKA,AXL,BLK,BMX,BTK,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK4,CLK4,CSF1R,DDR1,EGFR,EIF2AK3,EPHA2,ERBB2,ERBB4,FGFR1,FLT3,GAK,GRK2,IGF1R,INSR,INSRR,IRAK1,IRAK3,IRAK4,ITK,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP3K1,MAP3K11,MAP3K14,MAP3K21,MAP3K9,MAP4K1,MAP4K3,MAP4K5,MAPK10,MAPK7,MARK4,MELK,MET,MKNK2,NTRK1,PDGFRB,PDK1,PDK2,PDK4,PLK1,PLK2,PLK3,PLK4,PRKCD,PTK6,RET,RIPK3,SIK2,SIK3,SRC,STK33,SYK,TEK,TNK1,TTK,ULK1,YES1 75
kinase-selectivity-class AAK1,ALK,BLK,BMX,BTK,CAMK2A,CAMK2D,CSF1R,EGFR,ERBB2,ERBB4,FLT3,GAK,IGF1R,INSR,IRAK3,JAK3,LRRK2,MAP3K9,MAPK7,PDK4,PLK2,STK33,TNK1 24
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 2.958 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 12.417 High 0.89
mh-clint Mouse hepatocyte intrinsic clearance 44.978 High 0.89
mppb Mouse plasma protein binding (% unbound) 0.940 High 0.89
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 36.141 High 0.89
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 3.770 % High 0.89
rat-kpuu-brain Rat brain Kpuu 0.029 % High 1
rh-clint Rat hepatocyte intrinsic clearance 25.942 uL/min/10^6 cells High 0.89
rh-fuinc Rat hepatocyte fraction unbound in incubation 3.530 % High 0.89
rppb Rat plasma protein binding (% unbound) 1.020 % High 0.89
solubility-dd Solubility at pH 7.4 in DMSO 92.257 uM High 0.89

Approvals:

DateAgencyCompanyOrphan
Sept. 15, 2021 FDA TAKEDA PHARMS USA

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
Diarrhoea 173.71 43.03 114 901 939076 89688356
Metastases to central nervous system 54.72 43.03 16 999 17526 90609906
Dry skin 47.51 43.03 22 993 88051 90539381

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
Diarrhoea 88.32 52.87 53 339 460796 42160147

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
Diarrhoea 200.39 38.66 138 1193 1139367 109448601
Metastases to central nervous system 66.18 38.66 20 1311 22797 110565171
Dry skin 47.55 38.66 24 1307 107629 110480339
Non-small cell lung cancer 46.15 38.66 12 1319 7923 110580045
Rash 39.93 38.66 49 1282 820915 109767053
Death 39.39 38.66 45 1286 698824 109889144

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EB10 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
FDA MoA N0000020010 HER1 Antagonists
MeSH PA D000092004 Tyrosine Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000190118 Cytochrome P450 3A Inducers
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

L01EB Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors 8 drugs
afatinibdacomitiniberlotinibgefitinibicotiniblazertinibolmutinibosimertinib

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

DiseaseRelationSNOMED_IDDOID
Advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations indication 703228009




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 40MG BASE EXKIVITY TAKEDA PHARMS USA N215310 Sept. 15, 2021 DISCN CAPSULE ORAL 10227342 May 13, 2035 TREATMENT OF PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 20 EXON INSERTION MUTATIONS WHOSE DISEASE HAS PROGRESSED ON OR AFTER PLATINUM-BASED CHEMOTHERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 40MG BASE EXKIVITY TAKEDA PHARMS USA N215310 Sept. 15, 2021 DISCN CAPSULE ORAL Sept. 15, 2026 NEW CHEMICAL ENTITY
EQ 40MG BASE EXKIVITY TAKEDA PHARMS USA N215310 Sept. 15, 2021 DISCN CAPSULE ORAL Sept. 15, 2028 TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 20 INSERTION MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, WHOSE DISEASE HAS PROGRESSED ON OR AFTER PLATINUM-BASED CHEMOTHERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Epidermal growth factor receptor Kinase INHIBITOR Kd 6.67 DRUG LABEL DRUG LABEL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR IC50 9.40 DRUG LABEL DRUG LABEL
Tyrosine-protein kinase BTK Kinase INHIBITOR IC50 8.55 DRUG LABEL
Tyrosine-protein kinase JAK3 Kinase INHIBITOR IC50 8.66 DRUG LABEL
Tyrosine-protein kinase Blk Kinase INHIBITOR IC50 9.70 DRUG LABEL
Tyrosine-protein kinase TXK Kinase INHIBITOR IC50 8.64 DRUG LABEL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR IC50 10 DRUG LABEL

External reference:

IDSource
39HBQ4A67L UNII
2389149-74-8 SECONDARY_CAS_RN
C5418176 UMLSCUI
CHEBI:758219 CHEBI
CHEMBL4650319 ChEMBL_ID
118607832 PUBCHEM_CID
DB16390 DRUGBANK_ID
CHEMBL4802239 ChEMBL_ID
D12001 KEGG_DRUG
11183 INN_ID
C000720862 MESH_SUPPLEMENTAL_RECORD_UI
10468 IUPHAR_LIGAND_ID
40609711000001106 SNOMEDCT_US
40618011000001101 SNOMEDCT_US
4040829 VANDF
350405 MMSL
39900 MMSL
d09808 MMSL
018847 NDDF
018848 NDDF
2570736 RXNORM
39HBQ4A67L INXIGHT DRUGS

Pharmaceutical products:

None