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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H22FN7O3
Molecular Weight 463.4652
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMG-337

SMILES

C[C@]([H])(c1nnc2c(cc(cn12)-c3cnn(C)c3)F)n4ccc5c(cc(cn5)OCCOC)c4=O

InChI

InChIKey=DWHXUGDWKAIASB-CQSZACIVSA-N
InChI=1S/C23H22FN7O3/c1-14(30-5-4-20-18(23(30)32)9-17(11-25-20)34-7-6-33-3)21-27-28-22-19(24)8-15(13-31(21)22)16-10-26-29(2)12-16/h4-5,8-14H,6-7H2,1-3H3/t14-/m1/s1

HIDE SMILES / InChI

Molecular Formula C23H22FN7O3
Molecular Weight 463.4652
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27196749 | http://www.amgenoncology-international.com/#/our-products/our-pipeline/

AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the cell surface enzyme called c-Met, which, when dysregulated, stimulates cancer cell scattering, invasion and protection from apoptosis. AMG 337, currently in Phase 2 development for the treatment of gastric and esophageal adenocarcinoma. In addition, recently was shown, that AMG 337 a promising and novel therapeutic strategy for targeting hepatocellular carcinomas with a dependence on HGF/MET signaling.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed

Sample Use Guides

150 mg, 200 mg and 300 mg orally daily. Additional 150 mg and 200 mg orally twice daily.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: It was determined the effects of AMG 337 on the proliferation of a limited panel of cell lines with varying MET copy numbers, and was revealed that high-level focal MET amplification (>12 copies) was required to confer MET oncogene addiction and AMG 337 sensitivity. One MET-amplified cell line, H1573 (>12 copies), was AMG 337 insensitive, possibly because of a downstream G12A KRAS mutation. Mechanism-of-action studies in sensitive MET-amplified cell lines demonstrated that AMG 337 inhibited MET and adaptor protein Gab-1 phosphorylation, subsequently blocking the downstream PI3K and MAPK pathways.
Unknown
Substance Class Chemical
Created
by admin
on Sat Jun 26 13:53:10 UTC 2021
Edited
by admin
on Sat Jun 26 13:53:10 UTC 2021
Record UNII
08WG8S0L8D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMG-337
Common Name English
1,6-NAPHTHYRIDIN-5(6H)-ONE, 6-((1R)-1-(8-FLUORO-6-(1-METHYL-1H-PYRAZOL-4-YL)-1,2,4-TRIAZOLO(4,3-A)PYRIDIN-3-YL)ETHYL)-3-(2-METHOXYETHOXY)-
Systematic Name English
AMG 337 [WHO-DD]
Code English
Code System Code Type Description
ChEMBL
CHEMBL3545212
Created by admin on Sat Jun 26 13:53:10 UTC 2021 , Edited by admin on Sat Jun 26 13:53:10 UTC 2021
PRIMARY
CAS
1173699-31-4
Created by admin on Sat Jun 26 13:53:10 UTC 2021 , Edited by admin on Sat Jun 26 13:53:10 UTC 2021
PRIMARY
PUBCHEM
44181686
Created by admin on Sat Jun 26 13:53:10 UTC 2021 , Edited by admin on Sat Jun 26 13:53:10 UTC 2021
PRIMARY
DRUG BANK
DB15639
Created by admin on Sat Jun 26 13:53:10 UTC 2021 , Edited by admin on Sat Jun 26 13:53:10 UTC 2021
PRIMARY
FDA UNII
08WG8S0L8D
Created by admin on Sat Jun 26 13:53:10 UTC 2021 , Edited by admin on Sat Jun 26 13:53:10 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY