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GSK547 - 99%, high purity , CAS No.2226735-55-1, Inhibitor of receptor interacting serine/threonine kinase 1

Item Number
G414181
Grouped product items
SKUSizeAvailabilityPrice Qty
G414181-5mg
5mg
In stock
$117.90
G414181-25mg
25mg
In stock
$345.90
G414181-100mg
100mg
In stock
$741.90

RIP kinase Inhibitors

Basic Description

Specifications & PurityMoligand™, ≥99%
Biochemical and Physiological MechanismsGSK'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 TempStore at -20°C
Shipped InIce chest + Ice pads
GradeMoligand™
Action TypeINHIBITOR
Mechanism of actionInhibitor of receptor interacting serine/threonine kinase 1
Product Description

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 

Product Properties

ALogP2.776
Rotatable Bond3

Associated Targets(Human)

RIPK1 Tchem Receptor-interacting serine/threonine-protein kinase 1 (4 Activities)
Activity TypeActivity Value -log(M)Mechanism of ActionActivity ReferencePublications (PubMed IDs)

Associated Targets(non-human)

Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences
Receptor-interacting serine/threonine-protein kinase 1 inhibitorINHIBITORALA5464Receptor-interacting serine/threonine-protein kinase 1SINGLE PROTEINHomo sapiens

PubMed: [1]


Names and Identifiers

IUPAC Name 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile
INCHI 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
InChi Key SJVGFKBLUYAEOK-SFHVURJKSA-N
Canonical SMILES C1CN(CCC1C(=O)N2C(CC=N2)C3=CC(=CC(=C3)F)F)C4=NC=NC(=C4)C#N
Isomeric SMILES C1CN(CCC1C(=O)N2[C@@H](CC=N2)C3=CC(=CC(=C3)F)F)C4=NC=NC(=C4)C#N
PubChem CID 134521814
Molecular Weight 396.39

Certificates

C of A & Other Certificates

Find and download the COA for your product by matching the lot number on the packaging.

3 results found

Lot NumberCertificate TypeDateItem
K2218478Certificate of AnalysisAug 25, 2022 G414181
K2218479Certificate of AnalysisAug 25, 2022 G414181
K2218480Certificate of AnalysisAug 25, 2022 G414181

Chemical and Physical Properties

SolubilitySolubility (25°C) In vitro DMSO: 29 mg/mL (73.16 mM); Water: Insoluble; Ethanol: Insoluble;
DMSO(mg / mL) Max Solubility29
DMSO(mM) Max Solubility73.1602714498348
Water(mg / mL) Max Solubility<1

Safety and Hazards(GHS)

Pictogram(s) GHS07
Signal Warning
Hazard Statements

H315:Causes skin irritation

H319:Causes serious eye irritation

H335:May cause respiratory irritation

Precautionary Statements

P261:Avoid breathing dust/fume/gas/mist/vapors/spray.

P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do - continue rinsing.

Related Documents

References

1. Wang W, Marinis JM, Beal AM, Savadkar S, Wu Y, Khan M, Taunk PS, Wu N, Su W, Wu J et al..  (2018)  RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer..  Cancer Cell,  34  (5): (757-774.e7).  [PMID:30423296] [10.1021/op500134e]
2. Harris PA, Marinis JM, Lich JD, Berger SB, Chirala A, Cox JA, Eidam PM, Finger JN, Gough PJ, Jeong JU et al..  (2019)  Identification of a RIP1 Kinase Inhibitor Clinical Candidate (GSK3145095) for the Treatment of Pancreatic Cancer..  ACS Med Chem Lett,  10  (6): (857-862).  [PMID:31223438] [10.1021/op500134e]

Solution Calculators