infigratinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| tyrosine kinase inhibitors | 5459 | 872511-34-7 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
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.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 2 | Bocci G, Oprea TI, Benet LZ |
Predicted pharmacokinetic/toxicological properties (PK-AZ):
| Property | Description | Value | Unit | Confidence | Similarity |
|---|---|---|---|---|---|
| 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 |
| 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:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| 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 term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients 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:
| Source | Code | Description |
|---|---|---|
| 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|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| 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 strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| 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:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA 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:
| ID | Source |
|---|---|
| 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