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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H22FN7O3
Molecular Weight 463.4643
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMG-337

SMILES

COCCOC1=CC2=C(C=CN([C@H](C)C3=NN=C4N3C=C(C=C4F)C5=CN(C)N=C5)C2=O)N=C1

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 463.4643
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
Tracking the 2015 Gastrointestinal Cancers Symposium: bridging cancer biology to clinical gastrointestinal oncology.
2015
In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models.
2016 Jul
Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity.
2016 Mar 24

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 Dec 16 01:47:20 UTC 2023
Edited
by admin
on Sat Dec 16 01:47:20 UTC 2023
Record UNII
08WG8S0L8D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMG-337
Common Name English
AMG 337 [WHO-DD]
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
Code System Code Type Description
ChEMBL
CHEMBL3545212
Created by admin on Sat Dec 16 01:47:20 UTC 2023 , Edited by admin on Sat Dec 16 01:47:20 UTC 2023
PRIMARY
CAS
1173699-31-4
Created by admin on Sat Dec 16 01:47:20 UTC 2023 , Edited by admin on Sat Dec 16 01:47:20 UTC 2023
PRIMARY
PUBCHEM
44181686
Created by admin on Sat Dec 16 01:47:20 UTC 2023 , Edited by admin on Sat Dec 16 01:47:20 UTC 2023
PRIMARY
NCI_THESAURUS
C95203
Created by admin on Sat Dec 16 01:47:20 UTC 2023 , Edited by admin on Sat Dec 16 01:47:20 UTC 2023
PRIMARY
DRUG BANK
DB15639
Created by admin on Sat Dec 16 01:47:20 UTC 2023 , Edited by admin on Sat Dec 16 01:47:20 UTC 2023
PRIMARY
SMS_ID
100000175796
Created by admin on Sat Dec 16 01:47:20 UTC 2023 , Edited by admin on Sat Dec 16 01:47:20 UTC 2023
PRIMARY
FDA UNII
08WG8S0L8D
Created by admin on Sat Dec 16 01:47:20 UTC 2023 , Edited by admin on Sat Dec 16 01:47:20 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Little efficacy shown in Phase II trials.
IC50
SALT/SOLVATE -> PARENT
SOLVATE->ANHYDROUS
Related Record Type Details
ACTIVE MOIETY