GSK3179106 - ≥98% , CAS No.1627856-64-7

CAS: 1627856-64-7 Cat. No.: G414201 Molecular Weight: 467.41

GRADE & PURITY ≥98%

Synonyms

Benzeneacetamide, 4-(4-ethoxy-1,6-dihydro-6-oxo-3-pyridinyl)-2-fluoro-N-(5-(2,2,2-trifluoro-1,1-dimethylethyl)-3-isoxazolyl)- | DY8BBK4G3C | 1627856-64-7 | HY-100459 | RET Kinase inhibitor 1? | A930132 | 4-(4-Ethoxy-1,6-dihydro-6-oxo-3-pyridinyl)-2-fluoro

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

GSK3179106 GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small molecule RET (c-RET) kinase inhibitor with a RET IC50 of 0.3 nM and is efficacious in vivo.

Targets

RET (Cell-free assay) 0.3 nM

In vitro

GSK3179106 has a clean genotoxic profile with no embedded genotoxicity liabilities and possesses good kinase selectivity: only 26 out of a set of >300 recombinant kinases are found to be inhibited at a 1 μM test concentration.

In vivo

Single dose IV (bolus, 0.06 mg/kg) PK in male Sprague-Dawley rats of compound GSK3179106 formulated as 0.04 mg/mL in DMSO/6% HP-beta-CD = 5:95 with a pH of 7 as a clear solution shows low exposure with an AUC of 102 ng·h/mL. Oral PK is evaluated with the same dosing regimen as the in vivo colonic hypersensitivity model, seven doses of 10 mg/kg given over 3.5 days. Full gut PK measurements are also taken to help understand the PK/PD relationship--It reveals high concentrations of GSK3179106 in the colon contents, jejunum, duodenum, and ileum, over that in plasma.

Specifications

Synonyms

Benzeneacetamide, 4-(4-ethoxy-1, 6-dihydro-6-oxo-3-pyridinyl)-2-fluoro-N-(5-(2, 2, 2-trifluoro-1, 1-dimethylethyl)-3-isoxazolyl)- | DY8BBK4G3C | 1627856-64-7 | HY-100459 | RET Kinase inhibitor 1? | A930132 | 4-(4-Ethoxy-1, 6-dihydro-6-oxo-3-pyridinyl)-2-fluoro

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

GSK3179106 is a potent, selective, and gut-restricted pyridone hinge binder small molecule RET (c-RET) kinase inhibitor with a RET IC50 of 0.3 nM and is efficacious in vivo.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥98%

Product Properties

• ALogP: 3.357
• hba_count: 5
• HBD Count: 2
• Rotatable Bond: 8

Names and Identifiers

• Pubchem Sid: 504772441
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504772441
• Canonical Smiles: CCOC1=CC(=O)NC=C1C2=CC(=C(C=C2)CC(=O)NC3=NOC(=C3)C(C)(C)C(F)(F)F)F
• IUPAC Name: 2-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]acetamide
• InChIKey: IDXKJSSOUXWLDB-UHFFFAOYSA-N
• INCHI: 1S/C22H21F4N3O4/c1-4-32-16-9-19(30)27-11-14(16)12-5-6-13(15(23)7-12)8-20(31)28-18-10-17(33-29-18)21(2,3)22(24,25)26/h5-7,9-11H,4,8H2,1-3H3,(H,27,30)(H,28,29,31)
• Isomeric SMILES: CCOC1=CC(=O)NC=C1C2=CC(=C(C=C2)CC(=O)NC3=NOC(=C3)C(C)(C)C(F)(F)F)F
• Molecular Weight: 467.41
• Reaxy-Rn: 27483735
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=27483735&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Pyridines and derivatives
      • Subclass Phenylpyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Pyridines and derivatives
• Subclass: Phenylpyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpyridines
• Alternative Parents: Phenylacetamides N-arylamides Alkyl aryl ethers Pyridinones Dihydropyridines Fluorobenzenes Aryl fluorides Imidolactams Vinylogous esters Heteroaromatic compounds Isoxazoles Secondary carboxylic acid amides Lactams Oxacyclic compounds Azacyclic compounds Hydrocarbon derivatives Alkyl fluorides Organofluorides Carbonyl compounds Organic oxides
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 3-phenylpyridine - Phenylacetamide - N-arylamide - Alkyl aryl ether - Halobenzene - Pyridinone - Fluorobenzene - Dihydropyridine - Hydropyridine - Aryl fluoride - Aryl halide - Monocyclic benzene moiety - Imidolactam - Benzenoid - Isoxazole - Vinylogous ester - Azole - Heteroaromatic compound - Carboxamide group - Secondary carboxylic acid amide - Lactam - Ether - Azacycle - Carboxylic acid derivative - Oxacycle - Organonitrogen compound - Organooxygen compound - Alkyl fluoride - Organic nitrogen compound - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organofluoride - Alkyl halide - Organohalogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as phenylpyridines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyridine ring through a CC or CN 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

Associated Targets(Human)

RET Tclin Proto-oncogene tyrosine-protein kinase receptor Ret (2 Activities)

Discover Target: RET

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

KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)

Discover Target: KDR

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

RET Tclin Tyrosine-protein kinase receptor RET (6732 Activities)

Discover Target: RET

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

DDR1 Tchem Epithelial discoidin domain-containing receptor 1 (1050 Activities)

Discover Target: DDR1

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

Associated Targets(non-human)

Salmonella typhimurium (15756 Activities)

Explore this target

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

Rattus norvegicus (775804 Activities)

Explore this target

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

Mechanisms of Action

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 93 mg/mL (198.96 mM); Ethanol: 6 mg/mL (12.83 mM); Water: Insoluble
• DMSO(mg / mL) Max Solubility: 93
• DMSO(mM) Max Solubility: 198.968785434629
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 467.400 g/mol
• XLogP3: 3.400
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 7
• Exact Mass: 467.147 Da
• Monoisotopic Mass: 467.147 Da
• Topological Polar Surface Area: 93.500 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 812.000
• 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: 1