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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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SKU | Size | Availability | Price | Qty |
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G414181-5mg | 5mg | In stock | $117.90 | |
G414181-25mg | 25mg | In stock | $345.90 | |
G414181-100mg | 100mg | In stock | $741.90 |
RIP kinase Inhibitors
Specifications & Purity | Moligand™, ≥99% |
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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 Temp | Store at -20°C |
Shipped In | Ice chest + Ice pads |
Grade | Moligand™ |
Action Type | INHIBITOR |
Mechanism of action | Inhibitor 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 |
ALogP | 2.776 |
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Rotatable Bond | 3 |
Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
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IUPAC Name | 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile |
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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 |
Solubility | Solubility (25°C) In vitro DMSO: 29 mg/mL (73.16 mM); Water: Insoluble; Ethanol: Insoluble; |
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DMSO(mg / mL) Max Solubility | 29 |
DMSO(mM) Max Solubility | 73.1602714498348 |
Water(mg / mL) Max Solubility | <1 |
Pictogram(s) | GHS07 |
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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. |
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] |