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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5459 872511-34-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • infigratinib
  • infigratinib phosphate
  • truseltiq
  • BGJ-398
  • NVP-BGJ398
Infigratinib is a small molecule kinase inhibitor of FGFR with IC50 values of 1.1, 1, 2, and 61 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively. The major human metabolites of infigratinib, BHS697 and CQM157, have similar in vitro binding affinities for FGFR1, FGFR2, and FGFR3 compared to infigratinib. Infigratinib inhibited FGFR signaling and decreased cell proliferation in cancer cell lines with activating FGFR amplifications, mutations, or fusions. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Infigratinib had anti-tumor activity in mouse and rat xenograft models of human tumors with activating FGFR2 or FGFR3 alterations, including two patient-derived xenograft models of cholangiocarcinoma that expressed FGFR2-TTC28 or FGFR2-TRA2B fusions. Infigratinib demonstrated brain-to-plasma concentration ratios (based on AUC0-inf) of 0.682 in rats after a single oral dose.
  • Molecular weight: 560.48
  • Formula: C26H31Cl2N7O3
  • CLOGP: 5.44
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 2
  • TPSA: 95.09
  • ALOGS: -4.27
  • ROTB: 8

  • Status: OFM

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.212 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.506 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 20.654 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 20.277 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 5.300 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 19.460 % High 1
herg hERG pIC50 5.460 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 18.621 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 68.391 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 3.620 % High 1
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT2,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2B,CAMK2D,CDK1,CDK4,CDK5,CDK9,CHEK1,CSF1R,CSK,DDR1,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,ERBB4,FGFR1,FLT3,FYN,GAK,GRK2,INSR,IRAK1,ITK,JAK1,JAK2,KDR,KIT,LCK,LYN,MAP2K1,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K21,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK1,NTRK2,PAK4,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKCD,PRKDC,RIPK3,SGK1,SIK2,SIK3,SRC,STK33,SYK,TEK,TNIK,TTK,TYRO3,ULK1,ULK2,YES1 91
kinase-selectivity-class ACVR2A,ACVR2B,ALK,AURKA,AURKC,AXL,BLK,BRAF,CAMK2B,CAMK2D,CDK9,CSF1R,CSK,DDR1,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FGFR1,FGFR4,FLT3,FYN,GAK,GRK2,IRAK3,JAK1,KDR,KIT,LCK,LYN,MAP3K10,MAP3K21,MAP4K1,MAP4K3,MAPK7,MARK4,MET,MTOR,NTRK1,PDGFRB,PDK4,PIK3CD,PRKCD,SIK2,SIK3,SRC,STK10,STK33,TEK,TNIK,TTK,TYRO3,ULK1,ULK2,YES1 57
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 1.754 Moderate 0.74
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 9.727 High 1
mh-clint Mouse hepatocyte intrinsic clearance 69.343 High 1
mppb Mouse plasma protein binding (% unbound) 3.740 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 21.232 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 7.520 % High 1
rat-kpuu-brain Rat brain Kpuu 0.069 % Moderate 0.74
rh-clint Rat hepatocyte intrinsic clearance 101.391 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 25.530 % High 1
rppb Rat plasma protein binding (% unbound) 3.010 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 2.979 uM High 1

Approvals:

DateAgencyCompanyOrphan
June 28, 2019 FDA QED THERAP

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

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
Hyperphosphataemia 22.29 19.87 3 3 16378 110572915

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EN03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors
MeSH PA D000970 Antineoplastic Agents
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:63457 fibroblast growth factor receptor antagonist

Related Drugs by ATC class:

L01EN Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors 3 drugs

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

DiseaseRelationSNOMED_IDDOID
Unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion indication 312104005




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG TRUSELTIQ HELSINN HLTHCARE N214622 May 28, 2021 DISCN CAPSULE ORAL May 28, 2026 NEW CHEMICAL ENTITY
25MG TRUSELTIQ HELSINN HLTHCARE N214622 May 28, 2021 DISCN CAPSULE ORAL May 28, 2026 NEW CHEMICAL ENTITY
100MG TRUSELTIQ HELSINN HLTHCARE N214622 May 28, 2021 DISCN CAPSULE ORAL May 28, 2028 FOR TREATMENT OF ADULTS WITH PREVIOUSLY TREATED, UNRESECTABLE LOCALLY ADVANCED OR METASTATIC CHOLANGIOCARCINOMA WITH A FIBROBLAST GROWTH FACTOR RECEPTOR 2 (FGFR2) FUSION OR OTHER REARRANGEMENT AS DETECTED BY AN FDA-APPROVED TEST
25MG TRUSELTIQ HELSINN HLTHCARE N214622 May 28, 2021 DISCN CAPSULE ORAL May 28, 2028 FOR TREATMENT OF ADULTS WITH PREVIOUSLY TREATED, UNRESECTABLE LOCALLY ADVANCED OR METASTATIC CHOLANGIOCARCINOMA WITH A FIBROBLAST GROWTH FACTOR RECEPTOR 2 (FGFR2) FUSION OR OTHER REARRANGEMENT AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Fibroblast growth factor receptor 1 Kinase INHIBITOR 8.99 DRUG LABEL DRUG LABEL
Non-receptor tyrosine-protein kinase TYK2 Kinase IC50 5.48 CHEMBL
Macrophage-stimulating protein receptor Kinase IC50 5.54 CHEMBL
Tyrosine-protein kinase ABL1 Kinase IC50 5.64 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase IC50 6.12 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 5.53 CHEMBL
Tyrosine-protein kinase Lck Kinase IC50 5.60 CHEMBL
Tyrosine-protein kinase Yes Kinase IC50 5.96 CHEMBL
Tyrosine-protein kinase Fyn Kinase IC50 5.72 CHEMBL
Serine/threonine-protein kinase B-raf Kinase IC50 5.38 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase IC50 5.49 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 5.47 CHEMBL
Vascular endothelial growth factor receptor 1 Kinase IC50 5.82 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 6.74 IUPHAR
Vascular endothelial growth factor receptor 3 Kinase IC50 5.68 CHEMBL
Platelet-derived growth factor receptor alpha Kinase IC50 5.57 CHEMBL
BDNF/NT-3 growth factors receptor Kinase IC50 5.50 CHEMBL
Tyrosine-protein kinase JAK2 Kinase IC50 5.54 CHEMBL
Tyrosine-protein kinase SYK Kinase IC50 5.27 CHEMBL
Angiopoietin-1 receptor Kinase IC50 5.69 CHEMBL
Hepatocyte growth factor receptor Kinase IC50 5.52 CHEMBL
Tyrosine-protein kinase Lyn Kinase IC50 6.52 CHEMBL
Cytoplasmic tyrosine-protein kinase BMX Kinase IC50 5.47 CHEMBL
ALK tyrosine kinase receptor Kinase IC50 5.51 CHEMBL
Ephrin type-B receptor 1 Kinase IC50 5.52 CHEMBL
Proto-oncogene tyrosine-protein kinase ROS Kinase IC50 5.49 CHEMBL
Smoothened homolog GPCR Ki 7.33 CHEMBL
Fibroblast growth factor receptor 3 Kinase INHIBITOR 8.70 DRUG LABEL
Fibroblast growth factor receptor 2 Kinase INHIBITOR 9 DRUG LABEL
Fibroblast growth factor receptor 4 Kinase INHIBITOR 7.21 DRUG LABEL
Insulin receptor Kinase IC50 5.47 CHEMBL
Fibroblast growth factor receptor 4, FGFR-4, EC 2.7.10.1 Kinase IC50 6.27 CHEMBL

External reference:

IDSource
D11589 KEGG_DRUG
A4055ME1VK UNII
1310746-10-1 SECONDARY_CAS_RN
C3254591 UMLSCUI
07J PDB_CHEM_ID
CHEMBL1852688 ChEMBL_ID
53235510 PUBCHEM_CID
DB11886 DRUGBANK_ID
CHEMBL1834657 ChEMBL_ID
10032 INN_ID
C568950 MESH_SUPPLEMENTAL_RECORD_UI
7877 IUPHAR_LIGAND_ID
1162483003 SNOMEDCT_US
1162514000 SNOMEDCT_US
4040560 VANDF
CHEBI:750218 CHEBI
347055 MMSL
39550 MMSL
d09752 MMSL
018743 NDDF
018752 NDDF
2550729 RXNORM
A4055ME1VK INXIGHT DRUGS

Pharmaceutical products:

None