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Details

Stereochemistry ACHIRAL
Molecular Formula C22H25FN4O2
Molecular Weight 396.4579
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TOCERANIB

SMILES

CC1=C(C(=O)NCCN2CCCC2)C(C)=C(N1)\C=C3/C(=O)NC4=CC=C(F)C=C34

InChI

InChIKey=SRSGVKWWVXWSJT-ATVHPVEESA-N
InChI=1S/C22H25FN4O2/c1-13-19(12-17-16-11-15(23)5-6-18(16)26-21(17)28)25-14(2)20(13)22(29)24-7-10-27-8-3-4-9-27/h5-6,11-12,25H,3-4,7-10H2,1-2H3,(H,24,29)(H,26,28)/b17-12-

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23331696

Toceranib (toceranib phosphate) is an orally bioavailable small molecule inhibitor that blocks a variety of RTKs, including VEGFR2, PDGFRa and KIT. In non-clinical pharmacology studies, toceranib selectively inhibited the tyrosine kinase activity of several members of the split kinase receptor tyrosine kinase (RTK) family, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Toceranib inhibited the activity of Flk-1/KDR tyrosine kinase (vascular endothelial growth factor receptor, VEGFR2), platelet-derived growth factor receptor (PDGFR), and stem cell factor receptor (Kit) in both biochemical and cellular assays. Toceranib has been shown to exert an antiproliferative effect on endothelial cells in vitro. Toceranib treatment can induce cell cycle arrest and subsequent apoptosis in tumor cell lines expressing activating mutations in the split kinase RTK, ckit. Canine mast cell tumor growth is frequently driven by activating mutations in c-kit. Toceranib is a dog-specific anti-cancer drug approved by the U.S. Food and Drug Administration. It is marketed as Palladia as its phosphate salt, toceranib phosphate by Pfizer. PALLADIA (Toceranib) tablets are indicated for the treatment of Patnaik grade II or III, recurrent, cutaneous mast cell tumors with or without regional lymph node involvement in dogs.

Originator

Curator's Comment: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PALLADIA

Approved Use

PALLADIA tablets are indicated for the treatment of Patnaik grade II or III, recurrent, cutaneous mast cell tumors with or without regional lymph node involvement in dogs.

Launch Date

2009
PubMed

PubMed

TitleDatePubMed
Kinase dysfunction and kinase inhibitors.
2013 Feb
Patents

Patents

Sample Use Guides

Administer an initial dosage of 3.25 mg/kg (1.48 mg/lb) body weight, orally every other day. Dose reductions of 0.5 mg/kg (to a minimum dose of 2.2 mg/kg (1.0 mg/lb) every other day) and dose interruptions (cessation of PALLADIA for up to two weeks) may be utilized, if needed, to manage adverse reactions.
Route of Administration: Oral
Toceranib inhibited phosphorylation of WT (mouse) Kit in the presence of stem cell factor at concentrations as low as 0.01 uM.
Name Type Language
TOCERANIB
INN   MI   USAN  
INN   USAN  
Official Name English
5-[(Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide
Systematic Name English
toceranib [INN]
Common Name English
(Z)-5-((5-FLUORO-2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-N-(2-PYRROLIDIN-1-YLETHYL)-1H-PYRROLE-3-CARBOXAMIDE
Systematic Name English
PHA-291639
Code English
TOCERANIB [USAN]
Common Name English
TOCERANIB [MI]
Common Name English
PALLADIA
Brand Name English
1H-PYRROLE-3-CARBOXAMIDE, 5-((Z)-(5-FLUORO-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE)METHYL)-2,4-DIMETHYL-N-(2-(1-PYRROLIDINYL)ETHYL)-
Systematic Name English
TOCERANIB [EMA EPAR VETERINARY]
Common Name English
Classification Tree Code System Code
CFR 21 CFR 520.2475
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
NCI_THESAURUS C1967
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
EMA VETERINARY ASSESSMENT REPORTS PALLADIA [AUTHORIZED]
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
WHO-VATC QL01XE91
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL13608
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
SMS_ID
300000023713
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
USAN
TT-49
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
DAILYMED
59L7Y0530C
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
CAS
356068-94-5
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
INN
9069
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PRIMARY
FDA UNII
59L7Y0530C
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
PUBCHEM
5329106
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
MERCK INDEX
m10920
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY Merck Index
RXCUI
1145945
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY RxNorm
NCI_THESAURUS
C80870
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY
EPA CompTox
DTXSID50189076
Created by admin on Fri Dec 15 17:13:35 GMT 2023 , Edited by admin on Fri Dec 15 17:13:35 GMT 2023
PRIMARY