GSK547 - Moligand™, ≥99% , Inhibitor of receptor interacting serine/threonine kinase 1, CAS No.2226735-55-1, Inhibitor of receptor interacting serine/threonine kinase 1

CAS: 2226735-55-1 Cat. No.: G414181 Molecular Weight: 396.39

GRADE & PURITY Moligand™, ≥99%

Synonyms

4-​Pyrimidinecarbonitri​le,6-​[4-​[[(5S)​-​5-​(3,​5-​difluorophenyl)​-​4,​5-​dihydro-​1H-​pyrazol-​1-​yl]​carbonyl]​-​1-​piperidinyl]​-

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

GSK'547 GSK'547 is a highly selective and potent inhibitor of RIP1 (RIPK1) exhibiting a 400-fold improvement in mouse pharmacokinetic oral exposure compared with GSK'963

Targets

RIP1

In vitro

GSK\'547 (RIP1i) treatment in vitro directs the programming of bone marrow-derived macrophages (BMDM) toward an immunogenic phenotype, upregulating MHC-II, TNFa, and IFNg, while concomitantly reducing CD206, IL-10, and TGFb expression. Moreover, RIP1i upregulates STAT1 signaling in BMDM, which is associated with M1 programming, but reduced STAT3, STAT5, and STAT6 signaling, which are linked to M2-like macrophage differentiation. Furthermore, RIP1i-treated macrophages display enhanced ability to capture antigen.

In vivo

Administration of GSK\'547 (RIP1i) in mouse chow achieves in vivo steady-state concentrations above the L929 IC90 over a 24-hr period. High serum concentrations of RIP1i are sustained over a 6-week treatment course. RIP1i treatment is well tolerated without evident pathology. In mice challenged with orthotopic PDA (pancreatic ductal adenocarcinoma) tumor cells derived from KPC mice, RIP1i reduces tumor burden and extends survival cpmpared with mice treated with controls or Nec-1s. RIP1i also protects against established tumors and liver metastases.

Cell Research(from reference)

Cell lines：L929 cells 

Incubation Time：30 min 

Specifications

Synonyms

4-​Pyrimidinecarbonitri​le, 6-​[4-​[[(5S)​-​5-​(3, ​5-​difluorophenyl)​-​4, ​5-​dihydro-​1H-​pyrazol-​1-​yl]​carbonyl]​-​1-​piperidinyl]​-

Specifications & Purity

Moligand™, ≥99%

Biochemical and Physiological Mechanisms

GSK'547 is a highly selective and potent inhibitor of RIP1 (RIPK1) exhibiting a 400-fold improvement in mouse pharmacokinetic oral exposure compared with GSK'963

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.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of receptor interacting serine/threonine kinase 1

Purity

≥99%

Product Properties

• ALogP: 2.776
• hba_count: 4
• Rotatable Bond: 3

Names and Identifiers

• Pubchem Sid: 504773162
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504773162
• Canonical Smiles: C1CN(CCC1C(=O)N2C(CC=N2)C3=CC(=CC(=C3)F)F)C4=NC=NC(=C4)C#N
• IUPAC Name: 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile
• InChIKey: SJVGFKBLUYAEOK-SFHVURJKSA-N
• INCHI: 1S/C20H18F2N6O/c21-15-7-14(8-16(22)9-15)18-1-4-26-28(18)20(29)13-2-5-27(6-3-13)19-10-17(11-23)24-12-25-19/h4,7-10,12-13,18H,1-3,5-6H2/t18-/m0/s1
• Isomeric SMILES: C1CN(CCC1C(=O)N2[C@@H](CC=N2)C3=CC(=CC(=C3)F)F)C4=NC=NC(=C4)C#N
• Molecular Weight: 396.39
• Reaxy-Rn: 47354649
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=47354649&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Piperidines
      • Subclass Piperidinecarboxylic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Piperidines
• Subclass: Piperidinecarboxylic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Piperidinecarboxamides
• Alternative Parents: Dialkylarylamines Fluorobenzenes Aminopyrimidines and derivatives Imidolactams Pyrazolines Heteroaromatic compounds Amino acids and derivatives Vinyl fluorides Propargyl-type 1,3-dipolar organic compounds Nitriles Fluoroalkenes Carboximidamides Azacyclic compounds Amidines Organopnictogen compounds Organooxygen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Piperidinecarboxamide - Dialkylarylamine - Tertiary aliphatic/aromatic amine - Halobenzene - Fluorobenzene - Aminopyrimidine - Imidolactam - Benzenoid - Pyrimidine - Monocyclic benzene moiety - Heteroaromatic compound - Pyrazoline - Tertiary amine - Amino acid or derivatives - Azacycle - Fluoroalkene - Haloalkene - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Carboximidamide - Vinyl halide - Vinyl fluoride - Nitrile - Carbonitrile - Carboxylic acid derivative - Amidine - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as piperidinecarboxamides. These are compounds containing a piperidine ring substituted with a carboxamide functional group.
• 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)

RIPK1 Tchem Receptor-interacting serine/threonine-protein kinase 1 (4 Activities)

Discover Target: RIPK1

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

Associated Targets(non-human)

Mus musculus (284745 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: 29 mg/mL (73.16 mM); Water: Insoluble; Ethanol: Insoluble
• DMSO(mg / mL) Max Solubility: 29
• DMSO(mM) Max Solubility: 73.1602714498348
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 396.400 g/mol
• XLogP3: 1.900
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 3
• Exact Mass: 396.151 Da
• Monoisotopic Mass: 396.151 Da
• Topological Polar Surface Area: 85.500 Ų
• Heavy Atom Count: 29
• Formal Charge: 0
• Complexity: 663.000
• 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