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filgotinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| tyrosine kinase inhibitors | 5419 | 1206161-97-8 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Filgotinib is an adenosine triphosphate (ATP)-competitive and reversible inhibitor of the JAK family. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane. JAK1 is important in mediating inflammatory cytokine signals, JAK2 in mediating myelopoiesis and erythropoiesis and JAK3 plays critical roles in immune homeostasis and lymphopoiesis. Within the signalling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Filgotinib modulates these signalling pathways by preventing the phosphorylation and activation of STATs.
|
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.20 | g | O |
ADMET properties:
None
Predicted pharmacokinetic/toxicological properties (PK-AZ):
| Property | Description | Value | Unit | Confidence | Similarity |
|---|---|---|---|---|---|
| azlogd74 | LogD at pH 7.4 | 1.217 | High | 1 | |
| caco2-efflux | Caco-2 efflux ratio (BA/AB) | 19.011 | High | 1 | |
| caco2-intrinsic-papp | Caco-2 intrinsic apparent permeability | 15.596 | 10^-6 cm/s | High | 1 |
| dh-clint | Dog hepatocyte intrinsic clearance | 1.321 | uL/min/10^6 cells | High | 1 |
| dppb | Dog plasma protein binding (% unbound) | 52.130 | % | High | 1 |
| fcs-ppb | Fetal calf serum protein binding (% unbound) | 70.240 | % | High | 1 |
| herg | hERG pIC50 | 4.298 | pIC50 | High | 1 |
| hh-clint | Human hepatocyte intrinsic clearance | 1.629 | uL/min/10^6 cells | High | 1 |
| hlm-clint | Human liver microsomal intrinsic clearance | 4.395 | uL/min/mg protein | High | 1 |
| hppb | Human plasma protein binding (% unbound) | 47.580 | % | High | 1 |
| kinase-safety-class | ACVR2A,ACVR2B,ACVRL1,ALK,AXL,BRAF,CAMK2B,CAMK2D,CDK1,CDK9,CSF1R,DDR1,DYRK1B,EGFR,EIF2AK3,ERBB2,FLT3,GRK2,IRAK1,IRAK3,ITK,JAK1,KDR,KIT,MAP3K1,MAP3K10,MAP3K21,MAP4K1,MAP4K3,MAPK7,MARK4,NTRK1,PDK2,PDK4,PIK3CA,PIK3CD,PRKDC,SIK2,SIK3,TGFBR1,ULK1 | 41 | |||
| kinase-selectivity-class | ACVR2B,AURKA,AXL,CAMK2D,CDK1,CDK7,CDK9,DDR1,DYRK1B,EGFR,ERBB2,FLT3,IRAK1,IRAK3,KDR,MAP3K1,MAP3K10,MAP3K21,MAP4K1,MAP4K3,MAPK7,MET,NTRK1,PDK1,PIK3CD,SIK2,SIK3,TYRO3,ULK1 | 29 | |||
| mdck-mdr1-bcrp-efflux | MDCK-MDR1-BCRP efflux ratio | 27.861 | High | 1 | |
| mdck-mdr1-efflux | MDCK-MDR1 efflux ratio | 13.428 | High | 1 | |
| mh-clint | Mouse hepatocyte intrinsic clearance | 9.311 | High | 1 | |
| mppb | Mouse plasma protein binding (% unbound) | 39.890 | High | 1 | |
| nih-mdck-mdr1-efflux | NIH MDCK-MDR1 efflux ratio | 30.549 | High | 1 | |
| pfas-class | PFAS structural alert (1 = True, 0 = False) | 0 | |||
| pppb | Pig plasma protein binding (% unbound) | 61.910 | % | High | 1 |
| rat-kpuu-brain | Rat brain Kpuu | 0.008 | % | High | 1 |
| rh-clint | Rat hepatocyte intrinsic clearance | 3.573 | uL/min/10^6 cells | High | 1 |
| rh-fuinc | Rat hepatocyte fraction unbound in incubation | 87.290 | % | High | 1 |
| rppb | Rat plasma protein binding (% unbound) | 36.420 | % | High | 1 |
| solubility-dd | Solubility at pH 7.4 in DMSO | 23.605 | uM | High | 1 |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Sept. 24, 2020 | EMA | Gilead Sciences Ireland UC | |
| Sept. 25, 2020 | PMDA | Gilead Sciences |
FDA Adverse Event Reporting System (Female)
| 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 |
|---|---|---|---|---|---|---|
| Rhesus antigen positive | 71.14 | 49.06 | 9 | 822 | 125 | 90627491 |
| Blood albumin increased | 51.53 | 49.06 | 9 | 822 | 1176 | 90626440 |
| Blood immunoglobulin M decreased | 50.18 | 49.06 | 9 | 822 | 1368 | 90626248 |
FDA Adverse Event Reporting System (Male)
| 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 |
|---|---|---|---|---|---|---|
| Angiolymphoid hyperplasia with eosinophilia | 79.84 | 62.22 | 10 | 377 | 130 | 42620818 |
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 |
|---|---|---|---|---|---|---|
| Angiolymphoid hyperplasia with eosinophilia | 81.15 | 47.69 | 10 | 858 | 131 | 110588300 |
| Rhesus antigen positive | 72.54 | 47.69 | 9 | 859 | 125 | 110588306 |
| Diarrhoea haemorrhagic | 67.11 | 47.69 | 17 | 851 | 15622 | 110572809 |
| Enteropathic spondylitis | 52.74 | 47.69 | 6 | 862 | 37 | 110588394 |
| Blood albumin increased | 48.54 | 47.69 | 9 | 859 | 1922 | 110586509 |
| Blood immunoglobulin M decreased | 48.04 | 47.69 | 9 | 859 | 2032 | 110586399 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | L04AF04 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Janus-associated kinase (JAK) inhibitors |
| CHEBI has role | CHEBI:35842 | antirheumatic drug |
| CHEBI has role | CHEBI:66981 | ophthalmology drug |
| CHEBI has role | CHEBI:67079 | anti-inflammatory agent |
| CHEBI has role | CHEBI:231911 | renoprotective agent |
Related Drugs by ATC class:
L04AF Janus-associated kinase (JAK) inhibitors 7 drugs
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Ulcerative colitis | indication | 64766004 | DOID:8577 |
| Rheumatoid arthritis | indication | 69896004 | DOID:7148 |
| Active tuberculosis | contraindication | 427099000 |
🐶 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)
None
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Tyrosine-protein kinase JAK1 | Kinase | INHIBITOR | IC50 | 8 | SCIENTIFIC LITERATURE | DRUG LABEL | |||
| Tyrosine-protein kinase ABL1 | Kinase | IC50 | 5.64 | CHEMBL | |||||
| Receptor-type tyrosine-protein kinase FLT3 | Kinase | IC50 | 6.47 | CHEMBL | |||||
| Vascular endothelial growth factor receptor 1 | Kinase | IC50 | 5.88 | CHEMBL | |||||
| Vascular endothelial growth factor receptor 3 | Kinase | IC50 | 6.56 | CHEMBL | |||||
| Macrophage colony-stimulating factor 1 receptor | Kinase | IC50 | 6.31 | CHEMBL | |||||
| Mitogen-activated protein kinase 10 | Kinase | Kd | 5.67 | CHEMBL | |||||
| AP2-associated protein kinase 1 | Kinase | Kd | 5.30 | CHEMBL | |||||
| Serine/threonine-protein kinase 10 | Kinase | Kd | 5.72 | CHEMBL | |||||
| BMP-2-inducible protein kinase | Kinase | Kd | 5.18 | CHEMBL | |||||
| STE20-like serine/threonine-protein kinase | Kinase | Kd | 5.03 | CHEMBL | |||||
| Potassium voltage-gated channel subfamily H member 2 | Ion channel | IC50 | 4.07 | CHEMBL | |||||
| Tyrosine-protein kinase Mer | Kinase | IC50 | 5.89 | CHEMBL | |||||
| Serine/threonine-protein kinase TBK1 | Kinase | IC50 | 5.75 | CHEMBL | |||||
| Interleukin-1 receptor-associated kinase 1 | Kinase | Kd | 5.33 | CHEMBL | |||||
| Signal transducer and activator of transcription 1-alpha/beta | Transcription factor | IC50 | 6.20 | CHEMBL | |||||
| Uncharacterized protein FLJ45252 | Unclassified | Kd | 5.36 | CHEMBL | |||||
| Uncharacterized aarF domain-containing protein kinase 1 | Kinase | Kd | 5.69 | CHEMBL | |||||
| Tyrosine-protein kinase JAK3 | Kinase | INHIBITOR | IC50 | 6.09 | SCIENTIFIC LITERATURE | ||||
| Tyrosine-protein kinase JAK2 | Kinase | INHIBITOR | IC50 | 7.55 | SCIENTIFIC LITERATURE | ||||
| Non-receptor tyrosine-protein kinase TYK2 | Kinase | INHIBITOR | IC50 | 6.94 | SCIENTIFIC LITERATURE | ||||
| Calcium/calmodulin-dependent protein kinase kinase 2 | Kinase | Kd | 5.44 | CHEMBL | |||||
| Jak1 protein | Kinase | IC50 | 7.54 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| D11106 | KEGG_DRUG |
| 3XVL385Q0M | UNII |
| 1802998-75-9 | SECONDARY_CAS_RN |
| 1540859-07-1 | SECONDARY_CAS_RN |
| C4310256 | UMLSCUI |
| CHEBI:755290 | CHEBI |
| 2HB | PDB_CHEM_ID |
| CHEMBL3301607 | ChEMBL_ID |
| 49831257 | PUBCHEM_CID |
| DB14845 | DRUGBANK_ID |
| CHEMBL4298167 | ChEMBL_ID |
| CHEMBL3301602 | ChEMBL_ID |
| 9720 | INN_ID |
| C584571 | MESH_SUPPLEMENTAL_RECORD_UI |
| 7913 | IUPHAR_LIGAND_ID |
| 1287402009 | SNOMEDCT_US |
| 1287403004 | SNOMEDCT_US |
| 1287488005 | SNOMEDCT_US |
| 018759 | NDDF |
| 018760 | NDDF |
| 3XVL385Q0M | INXIGHT DRUGS |
Pharmaceutical products:
None