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

Stem definitionDrug idCAS RN
uracil type antineoplastics 4893 183204-74-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tipiracil
  • tipiracil hydrochloride
  • tipiracil HCl
tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase
  • Molecular weight: 242.66
  • Formula: C9H11ClN4O2
  • CLOGP: -0.30
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 3
  • TPSA: 85.29
  • ALOGS: -2.52
  • ROTB: 2
  • Status: OFP
    • 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 -1.013 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.426 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 2.183 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 2.773 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 80.290 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 55.050 % High 1
herg hERG pIC50 4.704 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.730 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.319 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 63.530 % High 1
kinase-safety-class ACVR2A,ACVR2B,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,CHEK1,CSF1R,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GRK3,GSK3B,ITK,JAK1,JAK2,KIT,MAP3K21,MAP3K7,MAP4K1,MAPK10,MAPK12,MAPK7,MAPK9,MARK4,MTOR,NTRK1,NTRK2,PDK1,PDK2,PDPK1,PIK3CB,PIK3CD,PIM2,PLK1,PLK2,PLK3,PLK4,PRKCD,PRKDC,PTK2,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1,ULK2 58
kinase-selectivity-class ACVR2B,AXL,BRAF,CDK9,GRK2,MAPK7,SIK2,STK33,TEK 9
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.455 High 1
mh-clint Mouse hepatocyte intrinsic clearance 4.009 High 1
mppb Mouse plasma protein binding (% unbound) 79.020 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 4.571 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 86.480 % High 1
rh-clint Rat hepatocyte intrinsic clearance 1.570 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 92.980 % High 1
rppb Rat plasma protein binding (% unbound) 70.530 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 966.051 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 22, 2015 FDA TAIHO ONCOLOGY INC
March 24, 2014 PMDA Taiho Pharmaceutical Co., Ltd.

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
Therapy partial responder 73.30 62.76 17 243 37044 110551995

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
FDA MoA N0000191869 Thymidine Phosphorylase Inhibitors
FDA EPC N0000191870 Thymidine Phosphorylase Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:90878 EC 2.4.2.4 (thymidine phosphorylase) inhibitor

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

DiseaseRelationSNOMED_IDDOID
Malignant tumor of stomach indication 363349007 DOID:10534
Malignant tumor of colon indication 363406005 DOID:219




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.78 acidic
pKa2 9.98 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL RE46284 Sept. 22, 2029 TREATMENT OF ADULTS WITH METASTATIC GASTRIC OR GJA PREVIOUSLY TREATED WITH AT LEAST TWO PRIOR LINES OF CHEMOTHERAPY THAT INCLUDED A FLUOROPYRIMIDINE, A PLATINUM, EITHER A TAXANE OR IRINOTECAN, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL RE46284 Sept. 22, 2029 TREATMENT OF METASTATIC COLORECTAL CANCER ALONE OR WITH BEVACIZUMAB IN PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN-BASED CHEMOTHERAPY, AN ANTI-VEGF BIOLOGICAL THERAPY, AND IF RAS WILD-TYPE, AN ANTI-EGFR THERAPY
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL RE46284 Sept. 22, 2029 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN-BASED CHEMOTHERAPY, AN ANTI-VEGF BIOLOGICAL THERAPY, AND IF RAS WILD-TYPE, AN ANTI-EGFR THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL RE46284 Sept. 22, 2029 TREATMENT OF ADULTS WITH METASTATIC GASTRIC OR GJA PREVIOUSLY TREATED WITH AT LEAST TWO PRIOR LINES OF CHEMOTHERAPY THAT INCLUDED A FLUOROPYRIMIDINE, A PLATINUM, EITHER A TAXANE OR IRINOTECAN, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL RE46284 Sept. 22, 2029 TREATMENT OF METASTATIC COLORECTAL CANCER ALONE OR WITH BEVACIZUMAB IN PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN-BASED CHEMOTHERAPY, AN ANTI-VEGF BIOLOGICAL THERAPY, AND IF RAS WILD-TYPE, AN ANTI-EGFR THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL RE46284 Sept. 22, 2029 TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER WHO HAVE BEEN PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN-BASED CHEMOTHERAPY, AN ANTI-VEGF BIOLOGICAL THERAPY, AND IF RAS WILD-TYPE, AN ANTI-EGFR THERAPY
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 9943537 Sept. 5, 2034 TREATMENT OF METASTATIC COLORECTAL CANCER WITH BEVACIZUMAB IN PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN-BASED CHEMOTHERAPY, AN ANTI-VEGF BIOLOGICAL THERAPY, AND IF RAS WILD-TYPE, AN ANTI-EGFR THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 9943537 Sept. 5, 2034 TREATMENT OF METASTATIC COLORECTAL CANCER WITH BEVACIZUMAB IN PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN-BASED CHEMOTHERAPY, AN ANTI-VEGF BIOLOGICAL THERAPY, AND IF RAS WILD-TYPE, AN ANTI-EGFR THERAPY
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10456399 Feb. 3, 2037 TREATMENT OF METASTATIC COLORECTAL CANCER ALONE OR WITH BEVACIZUMAB IN SEVERELY RENALLY IMPAIRED PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN THERAPY, AN ANTI-VEGF BIOLOGIC, AND IF RAS WILD-TYPE, ANTI-EGFR THERAPY
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10456399 Feb. 3, 2037 TREATMENT OF METASTATIC GASTRIC OR GJA IN SEVERELY RENALLY IMPAIRED PATIENTS TREATED WITH AT LEAST TWO LINES OF CHEMOTHERAPY THAT INCLUDED A FLUOROPYRIMIDINE, A PLATINUM, A TAXANE OR IRINOTECAN, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10960004 Feb. 3, 2037 TREATMENT OF METASTATIC COLORECTAL CANCER ALONE OR WITH BEVACIZUMAB IN SEVERELY RENALLY IMPAIRED PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN THERAPY, AN ANTI-VEGF BIOLOGIC, AND IF RAS WILD-TYPE, ANTI-EGFR THERAPY
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10960004 Feb. 3, 2037 TREATMENT OF METASTATIC GASTRIC OR GJA IN SEVERELY RENALLY IMPAIRED PATIENTS TREATED WITH AT LEAST TWO LINES OF CHEMOTHERAPY THAT INCLUDED A FLUOROPYRIMIDINE, A PLATINUM, A TAXANE OR IRINOTECAN, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10456399 Feb. 3, 2037 TREATMENT OF METASTATIC COLORECTAL CANCER ALONE OR WITH BEVACIZUMAB IN SEVERELY RENALLY IMPAIRED PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN THERAPY, AN ANTI-VEGF BIOLOGIC, AND IF RAS WILD-TYPE, ANTI-EGFR THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10456399 Feb. 3, 2037 TREATMENT OF METASTATIC GASTRIC OR GJA IN SEVERELY RENALLY IMPAIRED PATIENTS TREATED WITH AT LEAST TWO LINES OF CHEMOTHERAPY THAT INCLUDED A FLUOROPYRIMIDINE, A PLATINUM, A TAXANE OR IRINOTECAN, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10960004 Feb. 3, 2037 TREATMENT OF METASTATIC COLORECTAL CANCER ALONE OR WITH BEVACIZUMAB IN SEVERELY RENALLY IMPAIRED PATIENTS PREVIOUSLY TREATED WITH FLUOROPYRIMIDINE-, OXALIPLATIN- AND IRINOTECAN THERAPY, AN ANTI-VEGF BIOLOGIC, AND IF RAS WILD-TYPE, ANTI-EGFR THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL 10960004 Feb. 3, 2037 TREATMENT OF METASTATIC GASTRIC OR GJA IN SEVERELY RENALLY IMPAIRED PATIENTS TREATED WITH AT LEAST TWO LINES OF CHEMOTHERAPY THAT INCLUDED A FLUOROPYRIMIDINE, A PLATINUM, A TAXANE OR IRINOTECAN, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 6.14MG BASE;15MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL Feb. 22, 2026 TREATMENT OF ADULT PATIENTS WITH METASTATIC GASTRIC OR GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA PREVIOUSLY TREATED WITH AT LEAST TWO PRIOR LINES OF CHEMOTHERAPY, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY
EQ 8.19MG BASE;20MG LONSURF TAIHO ONCOLOGY N207981 Sept. 22, 2015 RX TABLET ORAL Feb. 22, 2026 TREATMENT OF ADULT PATIENTS WITH METASTATIC GASTRIC OR GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA PREVIOUSLY TREATED WITH AT LEAST TWO PRIOR LINES OF CHEMOTHERAPY, AND IF APPROPRIATE, HER2/NEU-TARGETED THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Thymidine phosphorylase Enzyme INHIBITOR IC50 7.70 SCIENTIFIC LITERATURE DRUG LABEL
Thymidine phosphorylase Enzyme IC50 7.70 CHEMBL

External reference:

IDSource
NGO10K751P UNII
D10467 KEGG_DRUG
183204-72-0 SECONDARY_CAS_RN
4034880 VANDF
C4056441 UMLSCUI
CHEBI:90879 CHEBI
CHEMBL235668 ChEMBL_ID
6323266 PUBCHEM_CID
DB09343 DRUGBANK_ID
CHEMBL65375 ChEMBL_ID
9500 INN_ID
C000613754 MESH_SUPPLEMENTAL_RECORD_UI
8696 IUPHAR_LIGAND_ID
1670303 RXNORM
31200 MMSL
d08381 MMSL
016454 NDDF
016455 NDDF
724029008 SNOMEDCT_US
724030003 SNOMEDCT_US
CMU PDB_CHEM_ID
NGO10K751P INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
LONSURF HUMAN PRESCRIPTION DRUG LABEL 2 64842-1020 TABLET, FILM COATED 8.19 mg ORAL NDA 27 sections
LONSURF HUMAN PRESCRIPTION DRUG LABEL 2 64842-1025 TABLET, FILM COATED 6.14 mg ORAL NDA 27 sections