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
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
| 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 |
DescriptionCurator'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/
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.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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
Edited
Sat Dec 16 01:47:20 GMT 2023
by
admin
on
Sat Dec 16 01:47:20 GMT 2023
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| Record UNII |
08WG8S0L8D
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| Record Status |
Validated (UNII)
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| Record Version |
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TARGET -> INHIBITOR |
Little efficacy shown in Phase II trials.
IC50
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SALT/SOLVATE -> PARENT |
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SOLVATE->ANHYDROUS |
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ACTIVE MOIETY |
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