MK-8033 hydrochloride - ≥99% , CAS No.1283000-43-0

CAS: 1283000-43-0 Cat. No.: M650978 Peso molecular: 508 PubChem CID: 51030992

GRADE & PURITY ≥99%

Storage

Store at 2-8°C,Desiccated

Shipped In

Wet ice

Descripción general

MK-8033 hydrochloride is an orally active ATP competitive c-Met/Ron dual inhibitor ( IC 50 s: 1 nM (c-Met),7 nM (Ron)), with preferential binding to the activated kinase conformation. MK-8033 hydrochloride can be used in the research of cancers, such as breast and bladder cancers, non-small cell lung cancers (NSCLCs)

In Vitro

MK-8033 hydrochloride (Compound 11r, 10 μM) displayed 31% inhibition of CYP3A4 (cytochrome P450 3A4). MK-8033 hydrochloride (1 μM, 2 h) inhibits phosphorylation of Y1349 of c-Met (IC 50 : 0.03 μM) in the c-Met dependent gastric cancer cell line GTL-16. MK-8033 hydrochloride (1-10 μM, 72 h) inhibits GTL-16 cell proliferation (IC 50 : 0.58 μM). MK-8033 hydrochloride binds more tightly to phosphorylated c-Met (K d : 3.2 nM) than to its unphosphorylated counterpart (K d : 10.4 nM), and inhibits oncogenic c-Met activation loop mutants with IC 50 s ranging from 0.6 to 1 nM. MK-8033 hydrochloride (0.1-10 μM, 2 h) reduces the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells. MK-8033 hydrochloride (1 μM, 1 h) sensitizes EBC-1 and H1993 cells (high c-Met-expressing) to radiation. MK-8033 hydrochloride (10 μM, 6 h) enhances γ-H2Ax levels in A549 cells compared to double irradiation and decreases in DNA repair. MK-8033 hydrochloride (2 μM, 72 h) results in reduced cell proliferation, but modest induction of apoptosis in G-alpha protein mutant UM (uveal melanoma) cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: EBC-1, H1993 cells, A549 and H460 cells Concentration: 0.1, 1, 10 μM Incubation Time: 2 h Result: Reduced the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells in a dose-dependent manner.

In Vivo

MK-8033 hydrochloride (Compound 11r, oral administration, 3-100 mg/kg, twice daily for 21 days) inhibits tumor growth in GTL-16 c-Met amplified gastric tumor xenografts . MK-8033 hydrochloride exhibits moderate clearance (t 1/2 : 0.8 h for rats, 3.1 h for dog) and favorable bioavailability (35% for rats, 33% for dog) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Human GTL-16 c-Met amplified gastric tumor xenografts Dosage: 3, 10, 30, and 100 mg/kg Administration: Oral administration, twice daily for 21 days Result: Resulted in 22, 18, 57, and 86% tumor growth inhibition at 3, 10, 30, and 100 mg/kg, respectively. Inhibited c-Met (Y1349) phosphorylation.

Form:Solid

IC50& Target:IC50: 7 nM (Ron)

Specifications

Especificaciones y pureza

≥99%

Mecanismos bioquímicos y fisiológicos

MK-8033 hydrochloride is an orally active ATP competitive c-Met/Ron dual inhibitor ( IC 50 s: 1 nM (c-Met), 7 nM (Ron)), with preferential binding to the activated kinase conformation. MK-8033 hydrochloride can be used in the research of cancers, such as b

Condiciones de almacenamiento de almacenamiento

Store at 2-8°C, Desiccated

Enviado en

Wet ice

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

Tipo de acción

INHIBITOR

Pureza

≥99%

Nombres e identificadores

• Sonrisas canónicas: CN1C=C(C=N1)C2=CC3=C(C=CC4=C(C3=O)C=C(C=C4)CS(=O)(=O)NCC5=CC=CC=N5)N=C2.Cl
• IUPAC Name: 1-[5-(1-methylpyrazol-4-yl)-2-oxo-7-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-14-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide;hydrochloride
• InChIKey: BKIQDRGTLKPYCL-UHFFFAOYSA-N
• INCHI: 1S/C25H21N5O3S.ClH/c1-30-15-20(13-28-30)19-11-23-24(27-12-19)8-7-18-6-5-17(10-22(18)25(23)31)16-34(32,33)29-14-21-4-2-3-9-26-21;/h2-13,15,29H,14,16H2,1H3;1H
• Isómeros SMILES: CN1C=C(C=N1)C2=CC3=C(C=CC4=C(C3=O)C=C(C=C4)CS(=O)(=O)NCC5=CC=CC=N5)N=C2.Cl
• PubChem CID: 51030992
• Peso molecular: 508

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: Tropones Organosulfonamides Organic sulfonamides Benzenoids Pyrazoles Heteroaromatic compounds Aminosulfonyl compounds Azacyclic compounds Organooxygen compounds Organonitrogen compounds Organic oxides Hydrochlorides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: 3-pyrazolylpyridine - Tropone - Organic sulfonic acid amide - Organosulfonic acid amide - Benzenoid - Azole - Pyrazole - Organic sulfonic acid or derivatives - Organosulfonic acid or derivatives - Sulfonyl - Aminosulfonyl compound - Heteroaromatic compound - Azacycle - Organooxygen compound - Organic oxygen compound - Organonitrogen compound - Organic oxide - Organosulfur compound - Hydrocarbon derivative - Organic nitrogen compound - Hydrochloride - 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

Propiedades químicas y físicas

• Solubilidad: H2O : 7.14 mg/mL (14.06 mM; Need ultrasonic) DMSO : 5.88 mg/mL (11.58 mM; Need ultrasonic)
• Peso molecular: 508.000 g/mol
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 507.113 Da
• Monoisotopic Mass: 507.113 Da
• Topological Polar Surface Area: 115.000 Ų
• Heavy Atom Count: 35
• Formal Charge: 0
• Complexity: 859.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• 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: 2

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