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Details

Stereochemistry ACHIRAL
Molecular Formula C22H25FN4O2.H3O4P
Molecular Weight 494.4531
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TOCERANIB PHOSPHATE

SMILES

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

InChI

InChIKey=AOORBROPMMRREB-HBPAQXCTSA-N
InChI=1S/C22H25FN4O2.H3O4P/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;1-5(2,3)4/h5-6,11-12,25H,3-4,7-10H2,1-2H3,(H,24,29)(H,26,28);(H3,1,2,3,4)/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
A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies.
2013 Oct
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 PHOSPHATE
MI   USAN  
USAN  
Official Name English
TOCERANIB PHOSPHATE [GREEN BOOK]
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 PHOSPHATE
Systematic 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)-, PHOSPHATE (1:1)
Systematic 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 phosphate (1:1)
Systematic Name English
PHA-291639E
Code English
TOCERANIB PHOSPHATE [USAN]
Common Name English
TOCERANIB PHOSPHATE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
Code System Code Type Description
FDA UNII
24F9PF7J3R
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
ChEMBL
CHEMBL13608
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
PUBCHEM
16034840
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
NCI_THESAURUS
C80871
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
USAN
TT-48
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
SMS_ID
300000023778
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
MESH
C464577
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
CAS
874819-74-6
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
MERCK INDEX
m10920
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY Merck Index
DAILYMED
24F9PF7J3R
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY
RXCUI
1145944
Created by admin on Fri Dec 15 16:10:39 GMT 2023 , Edited by admin on Fri Dec 15 16:10:39 GMT 2023
PRIMARY RxNorm