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GSK583 RIP kinase inhibitor

Name: GSK583
Brand: Selleck Chemicals
SKU: S8261
Rating: 5 (3 reviews)

Cat.No.S8261

GSK583 is a highly potent and selective inhibitor of RIP2 kinase with IC50 of 5 nM. This compound also inhibits both TNF-α and IL-6 production with IC50 of ~200 nM in explant cultures.

Chemical Structure

Molecular Weight: 398.45

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Quality Control

Batch: S826101 DMSO]79 mg/mL]false]Ethanol]28 mg/mL]false]Water]Insoluble]false Purity: 99.75%

Cited in Nature Medicine for its top-tier quality
COA
SDS
Datasheet

99.75

Related Targets	Bcl-2 Caspase PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras
Other RIP kinase Inhibitors	Necrostatin-1 (Nec-1) Necrostatin 2 racemate (Nec-1s) GSK872 Mito-TEMPO GSK'963 RIPA-56 GSK2982772 Resibufogenin HS-1371 GSK2983559 (compound 3)

Chemical Information, Storage & Stability

Molecular Weight	398.45	Formula	C₂₀H₁₉FN₄O₂S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1346547-00-9	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC(C)(C)S(=O)(=O)C1=CC2=C(C=CN=C2C=C1)NC3=NNC4=C3C=C(C=C4)F

Solubility

In vitro
Batch:

DMSO : 79 mg/mL (198.26 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 28 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	RIP2 (Cell-free assay) 5 nM RIP3 (Cell-free assay) 16 nM
In vitro	GSK583 possesses comparable binding affinity for RIP3 kinase as demonstrated by an in-house FP binding assay configured similarly to the RIP2 FP assay (RIP2 FP IC50 = 5 nM; RIP3 FP IC50 = 16 nM). Despite this potent biochemical activity against RIP3 kinase, this compound shows little or no inhibition of RIP3-dependent necroptotic cell death in a cellular assay up to 10 μM concentration. It potently and dose dependently inhibits MDP-stimulated tumor necrosis factor-alpha (TNFα) production with an IC50 = 8 nM in primary human monocytes. Following treatment with this chemical at 1 μM, little inhibition of pro-inflammatory signaling is observed upon activation of Toll-like receptors (TLR2, TLR4, TLR7) or cytokine receptors (IL-1R, TNFR) but complete inhibition is observed upon activation of both NOD1 and NOD2 receptors, which signal in a RIP2-dependent manner. Although it has excellent kinase selectivity, this compound does inhibit both the hERG channel and Cyp3A4, which precludes it from further progression as a drug candidate.
In vivo	GSK583 has low clearance, moderate volumes of distribution, and moderate oral bioavailability in both rat and mouse. Eventhough this compound would not produce a human phamacodynamic response within an acceptable dose range which precludes this molecule from further development as a drug candidate, the oral PK in rat and mouse provides sufficient systemic exposure for use as a preclinical in vivo tool molecule in an acute inflammation challenge model.
References	[1] https://pubmed.ncbi.nlm.nih.gov/27109867/

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