AMG 337 - Moligand™, ≥98% , Inhibitor of CYP3A4;Inhibitor of MET proto-oncogene; receptor tyrosine kinase, CAS No.1173699-31-4, Inhibitor of CYP3A4;Inhibitor of MET proto-oncogene; receptor tyrosine kinase

CAS: 1173699-31-4 Cat. No.: A413926 Peso molecular: 463.46

GRADE & PURITY Moligand™, ≥98%

Synonyms

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)- | AC-33036 | HY-18696 | SCHEMBL4304600 | UNII-08WG8S0L8D | NSC789223 | NSC-789223 | BDBM50157612 | GTPL8913 | AMG-33

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Descripción general

Information

AMG 337 AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the Met (c-Met) receptor with an IC50 of 1 nM.

Targets

MET receptor (Cell-free assay); MET(H1094R) (Cell-free assay); MET(M1250T) (Cell-free assay); MET(V1092I) (Cell-free assay) 1 nM; 1 nM ;4.7 nM; 21.5 nM

In vitro

AMG 337 potently inhibits the enzymatic activity of WT MET and a subset of MET mutants found in papillary renal cell carcinoma. The inability of AMG 337 to inhibit the Y1230 and D1228 mutants is likely the result of a disruption of the inactive confirmation of the activation loop in the MET kinase domain. AMG 337 also inhibits cell based HGF-induced MET phosphorylation in PC3 cells with IC50 of 5nM.AMG 337 inhibits proliferation in MET-dependent cancer cell lines. AMG 337 inhibits signaling through the PI3K and MAPK pathways in MET-amplified gastric cancer cell lines resulting in profound effects on cell proliferation and survival.

In vivo

AMG 337 exhibits impressive potency with >90% inhibition of Gab-1 phosphorylation at a dose of 0.75 mg/kg (32 nmol/L free-drug concentration). AMG 337 is well tolerated at continuously administered doses that corresponded with complete MET inhibition for 24 hours, suggesting that AMG 337 has the preclinical attributes required to test the role of MET in human cancer.

Cell Research(from reference)

Cell lines：Human cancer cell lines 

Concentrations：serial dilution(a top concentration of 3 mmol/L.) 

Incubation Time：72 h 

Specifications

Sinónimos

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)- | AC-33036 | HY-18696 | SCHEMBL4304600 | UNII-08WG8S0L8D | NSC789223 | NSC-789223 | BDBM50157612 | GTPL8913 | AMG-33

Especificaciones y pureza

Moligand™, ≥98%

Mecanismos bioquímicos y fisiológicos

AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the Met (c-Met) receptor with an IC50 of 1 nM.

Condiciones de almacenamiento de almacenamiento

Store at -20°C

Enviado en

Ice chest + Ice pads

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

Inhibitor of CYP3A4;Inhibitor of MET proto-oncogene; receptor tyrosine kinase

Pureza

≥98%

Nombres e identificadores

• Pubchem Sid: 504770296
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504770296
• Sonrisas canónicas: CC(C1=NN=C2N1C=C(C=C2F)C3=CN(N=C3)C)N4C=CC5=C(C4=O)C=C(C=N5)OCCOC
• IUPAC Name: 6-[(1R)-1-[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl]-3-(2-methoxyethoxy)-1,6-naphthyridin-5-one
• 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
• Isómeros SMILES: C[C@H](C1=NN=C2N1C=C(C=C2F)C3=CN(N=C3)C)N4C=CC5=C(C4=O)C=C(C=N5)OCCOC
• Peso molecular: 463.46
• Reaxy-Rn: 29325693
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=29325693&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Clase Pyridines and derivatives
      • Subclass Pyrazolylpyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Clase: Pyridines and derivatives
• Subclass: Pyrazolylpyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyrazolylpyridines
• Alternative Parents: Naphthyridines Triazolopyridines Pyridinones Alkyl aryl ethers Aryl fluorides Triazoles Pyrazoles Heteroaromatic compounds Lactams Dialkyl ethers Azacyclic compounds Organonitrogen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: 3-pyrazolylpyridine - Naphthyridine - Triazolopyridine - Alkyl aryl ether - Pyridinone - Aryl fluoride - Aryl halide - Azole - Heteroaromatic compound - 1,2,4-triazole - Triazole - Pyrazole - Lactam - Dialkyl ether - Ether - Azacycle - Organooxygen compound - Organic oxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organohalogen compound - Organofluoride - Organonitrogen compound - Aromatic heteropolycyclic compound
• Descripción: This compound belongs to the class of organic compounds known as pyrazolylpyridines. These are compounds containing a pyrazolylpyridine skeleton, which consists of a pyrazole linked (not fused) to a pyridine by a bond.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Objetivos asociados (humanos)

CYP3A4 Tclin Cytochrome P450 3A4 (1 Activities)

Discover Target: CYP3A4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MET Tclin Hepatocyte growth factor receptor (3 Activities)

Discover Target: MET

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MET Tclin Hepatocyte growth factor receptor (10718 Activities)

Discover Target: MET

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Objetivos asociados (no humanos)

Hdac6 Histone deacetylase 6 (222 Activities)

Discover Target: Hdac6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Canis familiaris (36305 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mus musculus (284745 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Rattus norvegicus (775804 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Plasma (328 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Liver microsome (341 Activities)

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Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mecanismos de acción

Propiedades químicas y físicas

• Solubilidad: Solubility (25°C) In vitro DMSO: 95 mg/mL (204.97 mM); Ethanol: 95 mg/mL (204.97 mM); Water: Insoluble
• Peso molecular: 463.500 g/mol
• XLogP3: 1.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 7
• Exact Mass: 463.177 Da
• Monoisotopic Mass: 463.177 Da
• Topological Polar Surface Area: 99.700 Ų
• Heavy Atom Count: 34
• Formal Charge: 0
• Complexity: 760.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 1
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1