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Compound Detail

CHEMBL2001019

PF-04217903
Phase I
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Phase I
OCCn1cc(-c2cnc3nnn(Cc4ccc5ncccc5c4)c3n2)cn1

Basic Information

ChEMBL ID CHEMBL2001019
Name PF-04217903
Phase Phase I
Structure Type MOL
InChI Key PDMUGYOXRHVNMO-UHFFFAOYSA-N

Known Names

MET TYROSINE KINASE INHIBITOR PF-04217903 Pf-04217903 PF-4217903
14
Targets
68
Activities
4
Assay Types
7
PK Parameters
20
Publications
3
Known Names
1
Indications
1
Mechanisms

Molecular Properties

372.4
MW (Da)
1.67
ALogP
9
HBA
1
HBD
107.4
PSA (Ų)
0.50
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Flags

Natural Product

Extended Properties

Molecular Formula C19H16N8O
MW 372.39
Aromatic Rings 5
Heavy Atoms 28
NP-Likeness -2.00

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Hepatocyte growth factor receptor inhibitor INHIBITOR Hepatocyte growth factor receptor

Indications

Neoplasms

Activity Summary

IC50 49 meas. best 8.51
Ki 15 meas. best 9.2
Kd 3 meas. best 8.7
EC50 1 meas. best 9.52

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Hepatocyte growth factor receptor
CHEMBL3717
EC50 9.52 9.52 0.3 1
Hepatocyte growth factor receptor
CHEMBL3717
Ki 9.2 7.2085 0.6 13
Hepatocyte growth factor receptor
CHEMBL3717
Kd 8.7 8.4667 2.0 3
Hepatocyte growth factor receptor
CHEMBL3717
IC50 8.51 8.0476 3.1 25
Unchecked
CHEMBL612545
IC50 8.19 8.0533 6.4 6
Hepatocyte growth factor receptor
CHEMBL5585
IC50 8.16 8.16 6.9 1
HT-29
CHEMBL384
IC50 8.15 8.15 7.0 1
HUVEC
CHEMBL613979
IC50 8.14 7.8733 7.3 3
Hepatocyte growth factor receptor
CHEMBL2046265
IC50 8.02 8.02 9.5 1
NCI-H441
CHEMBL1075542
IC50 7.96 7.93 11.0 2
GTL 16 cell line
CHEMBL612708
IC50 7.92 7.715 12.0 2
Unchecked
CHEMBL612545
Ki 7.89 7.65 13.0 2
NCI-H1993
CHEMBL1075527
IC50 7.52 7.495 30.0 2
Phosphodiesterase 3
CHEMBL2094125
IC50 5.89 5.525 1300.0 2
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
CHEMBL4409
IC50 5.57 5.57 2700.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.3 5.3 5000.0 1
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B
CHEMBL290
IC50 5.27 5.27 5360.0 1
cGMP-specific 3',5'-cyclic phosphodiesterase
CHEMBL2304402
IC50 5.09 5.09 8060.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 8.2 mL.min-1.kg-1 Rattus norvegicus
CL 1.48 mL.min-1.g-1 Homo sapiens
F 71.0 % Rattus norvegicus
Fu 0.16 - Homo sapiens
T1/2 3.7 hr Rattus norvegicus
T1/2 2.7 hr Homo sapiens
T1/2 0.05 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Hepatocyte growth factor receptor EC50 = 0.3 nM 9.52 Inhibition of c-Met kinase (unknown origin) assessed as decrease in phosphorylat... 27448775
Hepatocyte growth factor receptor Ki = 0.631 nM 9.2 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -
Hepatocyte growth factor receptor Kd = 2.0 nM 8.7 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878
Hepatocyte growth factor receptor Ki = 3.0 nM 8.52 Inhibition of His6-tagged human c-Met H1094R mutant expressed in Sf9 cells pre-i... 19459657
Hepatocyte growth factor receptor IC50 = 3.1 nM 8.51 Inhibition of human c-Met H1094R mutant expressed in mouse 3T3 cells assessed as... 19459657
Hepatocyte growth factor receptor IC50 = 3.1 nM 8.51 Inhibition of human c-Met H1094R mutant expressed in mouse NIH3T3 cells assessed... 22389468
Hepatocyte growth factor receptor IC50 = 4.0 nM 8.4 Inhibition of C-Met (unknown origin) using polu (Glu,Tyr)4:1 substrate after 30 ... 26005523
Hepatocyte growth factor receptor IC50 = 4.0 nM 8.4 LanthaScreen Assay: The kinase assay is based on the LanthaScreen technology. La... -
Hepatocyte growth factor receptor IC50 = 4.0 nM 8.4 Antagonist activity at c-MET receptor in human A549 cells assessed as inhibition... 22924734
Hepatocyte growth factor receptor Kd = 4.5 nM 8.35 Binding affinity to human c-Met catalytic domain (1051-1348 residues) expressed ... 19459657
Hepatocyte growth factor receptor Kd = 4.5 nM 8.35 Selectivity interaction (SPR measurement) EUB0000619a MET -
Hepatocyte growth factor receptor IC50 = 4.6 nM 8.34 Inhibition of c-Met phosphorylation in HGF-stimulated HUVEC cells incubated for ... 22389468
Hepatocyte growth factor receptor IC50 = 4.8 nM 8.32 Inhibition of c-Met (unknown origin) 26717201
Hepatocyte growth factor receptor Ki = 4.8 nM 8.32 Inhibition of recombinant human c-Met in presence of NADH by spectrophotometric ... 22389468
Hepatocyte growth factor receptor Ki = 4.8 nM 8.32 Affinity Biochemical interaction (Continuous-coupled spectrophotometric assay (d... -
Hepatocyte growth factor receptor IC50 = 4.8 nM 8.32 Inhibition of wild type endogenous c-Met in human A549 cells assessed as reducti... 19459657
Hepatocyte growth factor receptor IC50 = 5.0 nM 8.3 Inhibition of c-Met phosphorylation in HGF-stimulated human HT-29 cells incubate... 22389468
Hepatocyte growth factor receptor IC50 = 5.0 nM 8.3 Affinity On-target Cellular interaction (ELISA (c-Met phosphorylation in HT29 ce... -
Hepatocyte growth factor receptor Ki = 5.0 nM 8.3 Competitive inhibition of N-terminal His6-tagged recombinant human c-MET (974 to... 22924734
Hepatocyte growth factor receptor IC50 = 5.8 nM 8.24 Inhibition of wild type human c-Met expressed in human T47D cells assessed as re... 19459657

Literature References

PubMed DOI Target Context # Activities
22389468 10.1158/1535-7163.mct-11-0839 Unchecked 87
19459657 10.1021/bi900438w Hepatocyte growth factor receptor 28
19459657 10.1021/bi900438w Unchecked 23
22389468 10.1158/1535-7163.mct-11-0839 Hepatocyte growth factor receptor 23
22389468 10.1158/1535-7163.mct-11-0839 GTL 16 cell line 18
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
22389468 10.1158/1535-7163.mct-11-0839 U-87 MG 11
- 10.6019/CHEMBL4689842 Fibroblast 9
- 10.6019/CHEMBL4689842 U2OS 9
- 10.6019/CHEMBL4689842 HEK-293T 8
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
22389468 10.1158/1535-7163.mct-11-0839 HT-29 5
22389468 10.1158/1535-7163.mct-11-0839 SW-620 4
29191878 10.1126/science.aan4368 Unchecked 4
19459657 10.1021/bi900438w ALK tyrosine kinase receptor 4
22924734 10.1021/jm300967g Hepatocyte growth factor receptor 4
22924734 10.1021/jm300967g Rattus norvegicus 4
19459657 10.1021/bi900438w MAP kinase-activated protein kinase 5 3
19459657 10.1021/bi900438w Dual specificity tyrosine-phosphorylation-regulated kinase 2 3

Data from ChEMBL 36 via Core Engine