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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

Molecular Formula C22H25FN4O2
Molecular Weight 396.4579
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
60.0 nM [IC50]
1.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PALLADIA

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
Toceranib inhibited phosphorylation of WT (mouse) Kit in the presence of stem cell factor at concentrations as low as 0.01 uM.
Substance Class Chemical
Record UNII
59L7Y0530C
Record Status Validated (UNII)
Record Version