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Details

Stereochemistry ACHIRAL
Molecular Formula C19H16N8O.ClH
Molecular Weight 408.844
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PF-04217903 HYDROCHLORIDE

SMILES

Cl.OCCN1C=C(C=N1)C2=NC3=C(N=NN3CC4=CC=C5N=CC=CC5=C4)N=C2

InChI

InChIKey=HGQFZZOIHJTGJW-UHFFFAOYSA-N
InChI=1S/C19H16N8O.ClH/c28-7-6-26-12-15(9-22-26)17-10-21-18-19(23-17)27(25-24-18)11-13-3-4-16-14(8-13)2-1-5-20-16;/h1-5,8-10,12,28H,6-7,11H2;1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C19H16N8O
Molecular Weight 372.3833
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

PF-04217903 is a triazolopyrazine inhibitor of c-MET that displays anticancer chemotherapeutic and anti-metastatic activities. PF-04217903 inhibits cell proliferation, invasion, and migration as well as tumor growth in various cancer models. In animal models of pancreatic neuroendocrine tumors, this compound prevents lymph node metastasis. PF-04217903 had been in phase I clinical trials by Pfizer for the treatment of solid tumors. In 2011, the company discontinued the development of the compound.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
4.8 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
397 ng/mL
100 mg 2 times / day multiple, oral
PF-04217903 plasma
Homo sapiens
0.24 μg/mL
30 mg single, oral
PF-04217903 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1595 ng × h/mL
100 mg 2 times / day multiple, oral
PF-04217903 plasma
Homo sapiens
0.81 μg × h/mL
30 mg single, oral
PF-04217903 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
6.6 h
30 mg single, oral
PF-04217903 plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
16%
unknown
PF-04217903 plasma
Homo sapiens
16.4%
30 mg single, oral
PF-04217903 plasma
Homo sapiens

Doses

PubMed

Sample Use Guides

In Vivo Use Guide
Escalating doses of PF-04217903 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg BID to 1000 mg BID. A cycle is considered to be 21 days
Route of Administration: Oral
In Vitro Use Guide
Treatment with 100 nM of PF-04217903 for 4 hours resulted in decreased p-MET, pERK, p-AKT and p-PLCγ1 in mouse melanocytes expressing TRIM4-MET or ZKSCAN1-MET
Substance Class Chemical
Record UNII
EA0E6NGB9V
Record Status Validated (UNII)
Record Version