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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5343 1029044-16-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • pexidartinib
  • pexidartinib hydrochloride
  • PLX3397
  • CML-261
  • turalio
Pexidartinib is a small molecule tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium. In vitro, pexidartinib inhibited proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R. Pexidartinib also inhibited the proliferation of a CSF1R dependent cell line in vivo.
  • Molecular weight: 417.82
  • Formula: C20H15ClF3N5
  • CLOGP: 4.39
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 2
  • TPSA: 66.49
  • ALOGS: -5.12
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.50 g O

ADMET properties:

PropertyValueReference
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ
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 4.722 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.718 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 12.023 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 25.003 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.390 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.770 % High 1
herg hERG pIC50 5.543 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 7.047 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 22.182 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.280 % High 1
kinase-safety-class AAK1,ABL2,ACVR2A,ACVR2B,ACVRL1,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK2,CDK3,CDK4,CDK5,CDK6,CDK7,CDK9,CHEK1,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,DYRK2,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FGFR1,FLT3,FLT4,FYN,GAK,GRK1,GRK2,GSK3A,GSK3B,HASPIN,IKBKB,INSR,IRAK1,IRAK3,ITK,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K2,MAP3K21,MAP3K3,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK7,MAPK8,MAPK9,MARK4,MELK,MET,MINK1,MST1R,MTOR,NTRK1,NTRK2,NTRK3,NUAK1,PAK4,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PIM3,PRKAA1,PRKAA2,PRKCD,PRKDC,ROCK1,RPS6KA1,SGK1,SIK2,SIK3,SRC,STK10,STK17A,STK33,STK4,SYK,TEK,TGFBR1,TNIK,TTK,TYRO3,UHMK1,ULK1,ULK2,YES1 129
kinase-selectivity-class AAK1,ACVR2B,AURKA,AURKB,AXL,BRAF,CAMK2B,CAMK2D,CDK1,CDK2,CDK7,CDK9,DYRK1B,FGFR1,FLT3,JAK1,JAK2,KDR,LRRK2,MAP3K10,MAP3K11,MAP3K21,MAP4K1,MAP4K3,MAPK7,MARK4,MELK,MET,NTRK1,NTRK3,PDK1,SIK2,SIK3,STK33,SYK,TTK,ULK1 37
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 3.451 High 1
mh-clint Mouse hepatocyte intrinsic clearance 35.810 High 1
mppb Mouse plasma protein binding (% unbound) 0.330 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 5.260 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 1
pppb Pig plasma protein binding (% unbound) 0.760 % High 1
rh-clint Rat hepatocyte intrinsic clearance 24.266 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 2.560 % High 1
rppb Rat plasma protein binding (% unbound) 0.250 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.368 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 2, 2019 FDA DAIICHI SANKYO INC

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
Hair colour changes 407.70 39.71 68 1583 3426 90623370
Product dose omission issue 135.76 39.71 77 1574 291610 90335186
Gamma-glutamyltransferase increased 87.87 39.71 31 1620 37921 90588875
Aspartate aminotransferase increased 84.73 39.71 40 1611 102897 90523899
Blood alkaline phosphatase increased 84.32 39.71 32 1619 48047 90578749
Alanine aminotransferase increased 76.49 39.71 39 1612 118299 90508497
Periorbital swelling 57.21 39.71 14 1637 4784 90622012
Fatigue 54.61 39.71 84 1567 1153939 89472857
Therapy cessation 52.37 39.71 21 1630 36340 90590456

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
Hair colour changes 304.09 56.83 49 680 2153 42618453
Product dose omission issue 104.30 56.83 51 678 154314 42466292

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
Hair colour changes 261.15 40.90 44 986 4657 110583612
Product dose omission issue 97.68 40.90 51 979 321731 110266538
Aspartate aminotransferase increased 71.21 40.90 33 997 159903 110428366
Blood alkaline phosphatase increased 63.15 40.90 24 1006 70911 110517358
Alanine aminotransferase increased 52.30 40.90 28 1002 183745 110404524
Gamma-glutamyltransferase increased 51.88 40.90 20 1010 61289 110526980
Fatigue 44.19 40.90 55 975 1215903 109372366

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EX15 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Other protein kinase inhibitors
FDA MoA N0000020001 Tyrosine Kinase Inhibitors
FDA MoA N0000020036 Colony Stimulating Factor Receptor Type 1 (CSF-1R) Inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000182139 Cytochrome P450 2B6 Inhibitors
FDA MoA N0000190118 Cytochrome P450 3A Inducers
FDA MoA N0000191272 UGT1A1 Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35842 antirheumatic drug
CHEBI has role CHEBI:62434 EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor

Related Drugs by ATC class:

L01EX Other protein kinase inhibitors 21 drugs
avapritinibcabozantinibcapivasertibentrectinibgilteritiniblarotrectiniblenvatinibmidostaurinnintedanibpazopanibpralsetinibquizartinib show all 21 →

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

DiseaseRelationSNOMED_IDDOID
Tenosynovial giant cell tumor indication 128777004




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.65 acidic
pKa2 6.1 Basic
pKa3 2.77 Basic
pKa4 0.39 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 125MG BASE TURALIO DAIICHI SANKYO INC N211810 Oct. 14, 2022 RX CAPSULE ORAL 8461169 April 19, 2028 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
EQ 200MG BASE TURALIO DAIICHI SANKYO INC N211810 Aug. 2, 2019 DISCN CAPSULE ORAL 8461169 April 19, 2028 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
EQ 125MG BASE TURALIO DAIICHI SANKYO INC N211810 Oct. 14, 2022 RX CAPSULE ORAL 9358235 June 8, 2033 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
EQ 200MG BASE TURALIO DAIICHI SANKYO INC N211810 Aug. 2, 2019 DISCN CAPSULE ORAL 9358235 June 8, 2033 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
EQ 125MG BASE TURALIO DAIICHI SANKYO INC N211810 Oct. 14, 2022 RX CAPSULE ORAL 10189833 May 5, 2036 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
EQ 200MG BASE TURALIO DAIICHI SANKYO INC N211810 Aug. 2, 2019 DISCN CAPSULE ORAL 10189833 May 5, 2036 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
EQ 125MG BASE TURALIO DAIICHI SANKYO INC N211810 Oct. 14, 2022 RX CAPSULE ORAL 10961240 July 24, 2038 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
EQ 200MG BASE TURALIO DAIICHI SANKYO INC N211810 Aug. 2, 2019 DISCN CAPSULE ORAL 10961240 July 24, 2038 TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 125MG BASE TURALIO DAIICHI SANKYO INC N211810 Oct. 14, 2022 RX CAPSULE ORAL Aug. 2, 2026 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 200MG BASE TURALIO DAIICHI SANKYO INC N211810 Aug. 2, 2019 DISCN CAPSULE ORAL Aug. 2, 2026 INDICATED FOR THE TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Mast/stem cell growth factor receptor Kit Kinase INHIBITOR IC50 7.56 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Receptor-type tyrosine-protein kinase FLT3 Kinase INHIBITOR IC50 6.79 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Macrophage colony-stimulating factor 1 receptor Kinase INHIBITOR IC50 7.88 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 6.36 IUPHAR
Platelet-derived growth factor receptor alpha Kinase IC50 8.02 CHEMBL
AP2-associated protein kinase 1 Kinase Kd 4.86 CHEMBL
Protein kinase C theta type Kinase Kd 8.22 CHEMBL
Platelet-derived growth factor receptor beta Kinase IC50 7.44 CHEMBL
Aurora kinase B Kinase IC50 6.19 CHEMBL
Cyclin-dependent kinase 19 Kinase INHIBITOR IC50 6.85 IUPHAR
Uncharacterized protein FLJ45252 Unclassified Kd 5.84 CHEMBL
NT-3 growth factor receptor Kinase INHIBITOR IC50 6.05 IUPHAR
Tyrosine-protein kinase Lck Kinase INHIBITOR IC50 6.07 IUPHAR
Vascular endothelial growth factor receptor 1 Kinase INHIBITOR IC50 6.06 IUPHAR
Macrophage colony-stimulating factor 1 receptor Kinase IC50 7.85 CHEMBL

External reference:

IDSource
6783M2LV5X UNII
2040295-03-0 SECONDARY_CAS_RN
4038623 VANDF
C4287804 UMLSCUI
CHEBI:145373 CHEBI
P30 PDB_CHEM_ID
CHEMBL3813873 ChEMBL_ID
25151352 PUBCHEM_CID
DB12978 DRUGBANK_ID
CHEMBL3989973 ChEMBL_ID
D11270 KEGG_DRUG
10056 INN_ID
C000600259 MESH_SUPPLEMENTAL_RECORD_UI
8710 IUPHAR_LIGAND_ID
789180004 SNOMEDCT_US
789195002 SNOMEDCT_US
321181 MMSL
37252 MMSL
d09340 MMSL
018075 NDDF
018076 NDDF
2183102 RXNORM
6783M2LV5X INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Turalio HUMAN PRESCRIPTION DRUG LABEL 1 65597-407 CAPSULE 125 mg ORAL NDA 35 sections