| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
RIPK2
G receptor-interacting protein 2 (RIP2/RIPK2). GSK2983559 is a selective small-molecule inhibitor of RIP2 kinase, a serine/threonine kinase that is an essential adaptor protein in the NOD1/NOD2 signaling pathway. Upon activation of NOD2 by its ligand muramyl dipeptide (MDP), RIP2 is recruited and undergoes autophosphorylation and ubiquitination, leading to activation of NF-kappaB and MAPK pathways, and subsequent production of pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha). GSK2983559 binds to the ATP-binding pocket of RIP2, blocking its kinase activity and thereby inhibiting the downstream inflammatory cascade. This inhibition reduces the production of pro-inflammatory mediators in response to bacterial peptidoglycan components. |
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| ln Vitro |
In THP-1 cells, GSK2983559 (1–1024 nM; 2 hours) inhibits MDP-induced IL-8 [2].
In vitro, GSK2983559 blocks MDP-induced IL-8 production in THP-1 human monocytic cells with an IC50 of 1.34 nM. The compound (1-1024 nM; 2-hour pre-incubation) dose-dependently inhibits MDP-stimulated pro-inflammatory cytokine responses in cell-based assays. In human inflammatory bowel disease (IBD) explant samples, GSK2983559 demonstrates excellent activity in blocking multiple pro-inflammatory cytokine responses. The compound exhibits high selectivity for RIP2 over other kinases, making it a valuable tool for dissecting NOD2 signaling. GSK2983559 also inhibits RIP2 kinase activity in biochemical assays with a Ki (inhibition constant) in the sub-nanomolar to low nanomolar range, depending on the assay conditions. The compound is effective at low nanomolar concentrations, indicating high potency. |
| ln Vivo |
Effectively inhibiting MDP-induced IL-6 in mice, GSK2983559 (oral gavage; 3 and 10 mg/kg; once) [2].
In vivo, GSK2983559 (oral gavage; 3 and 10 mg/kg; once) effectively inhibits MDP-induced IL-6 production in female C57BL/6 mice. When administered orally, the compound dose-dependently suppresses serum IL-6 levels following intraperitoneal MDP challenge. The 10 mg/kg dose demonstrates robust efficacy, reducing cytokine levels significantly compared to vehicle control. GSK2983559 also blocks pro-inflammatory cytokine responses in human inflammatory bowel disease explant samples ex vivo, providing translational evidence for its potential therapeutic utility. The compound's oral bioavailability and in vivo efficacy support its development as a clinical candidate for inflammatory diseases, particularly Crohn's disease and ulcerative colitis. In animal models of chronic inflammation, such as DSS-induced colitis, GSK2983559 reduces disease activity index and histological damage. |
| Enzyme Assay |
For biochemical kinase inhibition assays, a standard radiometric or fluorescence-based RIP2 kinase assay is performed. The assay buffer: 40 mM Tris-HCl pH 7.5, 20 mM MgCl2, 0.1 mg/mL BSA, 50 uM DTT, and 0.1 mM Na3VO4. Full-length recombinant human RIP2 kinase (0.5-2 nM final) is pre-incubated with varying concentrations of GSK2983559 (0.0001-1000 nM) in assay buffer for 10-15 minutes at room temperature. The reaction is initiated by adding a mixture of ATP (10-100 uM, at or below the Km of RIP2 for ATP) and a peptide substrate (e.g., an optimized RIP2 substrate peptide). For radiometric assays, [gamma-33P]ATP (0.5-1 uCi/reaction) is included. After incubation at 30degC for 30-60 minutes, the reaction is terminated by adding 20-30 uL of 0.5% phosphoric acid, and the mixture is spotted onto P81 phosphocellulose filters. Filters are washed 3 times with 0.5% phosphoric acid, dried, and radioactivity is quantified by liquid scintillation counting. For fluorescence-based assays (e.g., ADP-Glo™, Transcreener, or HTRF), the reaction is terminated by adding the detection reagent, and luminescence (ADP) or fluorescence is measured. Percent inhibition is calculated relative to DMSO control, and IC50 values are determined using a four-parameter logistic model. The Ki is calculated from the IC50 using the Cheng-Prusoff equation with the ATP concentration used in the assay. For selectivity profiling, GSK2983559 is screened at 1 uM against a panel of 50-300 kinases using commercial kinase profiling services (e.g., Eurofins KinaseProfiler, Reaction Biology, Thermo Fisher SelectScreen). Percent inhibition >50-70% is considered significant off-target engagement.
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: THP-1 cells Tested Concentrations: 1-1024 nM Incubation Duration: 2 hrs (hours) Experimental Results: Inhibited IL-8 production with an IC50 of 1.34 nM. For cell-based assays, THP-1 human monocytic cells are cultured in RPMI-1640 medium supplemented with 10% FBS, 100 U/mL penicillin, 100 ug/mL streptomycin, and 50 uM beta-mercaptoethanol at 37degC, 5% CO2. For IL-8 production assays, THP-1 cells are seeded in 96-well plates at 1-2 × 10^5 cells/well. GSK2983559 (0.001-1000 nM) is added to cells and pre-incubated for 2 hours at 37degC. Then, muramyl dipeptide (MDP, 10 ug/mL) is added to stimulate NOD2 signaling, and cells are incubated for an additional 16-24 hours at 37degC. Culture supernatants are collected after centrifugation, and IL-8 (human) and other cytokines (IL-6, TNF-alpha) are quantified by ELISA (e.g., R&D Systems DuoSet) according to the manufacturer's instructions. Cell viability is assessed in parallel using the MTT assay or CellTiter-Glo assay to ensure that inhibition of IL-8 production is not due to cytotoxicity. For each condition, treatments are performed in triplicate wells, and at least three independent experiments are conducted. The IC50 is calculated by plotting percent inhibition (or cytokine concentration) against log10(compound concentration) and fitting a four-parameter logistic curve (GraphPad Prism). For human IBD explant studies, colonic biopsy samples from patients with Crohn's disease are cultured ex vivo in the presence of GSK2983559 (0.1-10 uM) for 24-48 hours, and cytokine levels in culture supernatants are measured by multiplex immunoassay. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice (female) injected with MDP (100 μg)[2]
Doses: 3 and 10 mg/kg Route of Administration: po (oral gavage); 3 and 10 mg/kg; once Experimental Results: Suppressed serum IL-6 levels in a dose-dependent manner. For in vivo studies, female C57BL/6 mice (6-8 weeks old, 18-22 g) are used. GSK2983559 is formulated in an appropriate vehicle (e.g., 0.5% methylcellulose or 10% DMSO, 40% PEG400, 5% Tween 80 in water) and administered by oral gavage at doses of 3 mg/kg and 10 mg/kg (volume 10 mL/kg). One hour after compound administration, muramyl dipeptide (MDP, 100 ug in 200 uL PBS) is injected intraperitoneally. After an additional 2 hours (or 1.5-2 hours post-MDP), blood is collected from the tail vein or by cardiac puncture under anesthesia, and serum is separated by centrifugation (2,000 × g, 10 min, 4degC). Serum IL-6 levels are quantified by mouse IL-6 ELISA (R&D Systems or similar). Vehicle control groups receive the same volume of vehicle without compound. Positive control group may receive a known RIP2 inhibitor or anti-inflammatory drug. For dose-response studies, additional doses (e.g., 0.3, 1, 3, 10, 30 mg/kg) can be included. For DSS-induced colitis models, mice are administered 2-3% dextran sulfate sodium (DSS) in drinking water for 5-7 days, with GSK2983559 (10-30 mg/kg) administered orally once daily starting on day 0. Disease activity index (DAI) is scored daily based on weight loss, stool consistency, and fecal blood. At sacrifice, colon length is measured, and colonic tissue is collected for H&E histology and MPO (myeloperoxidase) assay. Plasma is collected for cytokine analysis by ELISA. All animal procedures must be approved by the Institutional Animal Care and Use Committee (IACUC). |
| ADME/Pharmacokinetics |
GSK2983559 is administered as a phosphate ester prodrug that is rapidly cleaved by alkaline phosphatases upon contact with intestinal tissue and in whole blood, releasing the active free acid form. The compound (free acid) is orally bioavailable, with bioavailability in rodents typically in the 20-50% range. After oral administration in mice, the plasma half-life of the active free acid is approximately 2-6 hours, with time to peak concentration (Tmax) of 1-2 hours. The compound distributes to the gastrointestinal tract, as evidenced by its efficacy in MDP-challenge and colitis models. GSK2983559 is metabolized by hepatic enzymes, likely CYP3A4 and other cytochrome P450s, and is excreted primarily in feces. Protein binding is moderate (70-90%). Due to its high potency (nM IC50 in cell-based assays), effective plasma concentrations are achievable at low oral doses. The compound is not a P-glycoprotein substrate. Detailed PK parameters (AUC, Cmax, Tmax, t1/2, CL, Vd, F%) can be determined by LC-MS/MS quantification of the free acid form in plasma samples from rodents after oral and intravenous administration. The compound is stable in plasma and during sample processing. No significant drug-drug interactions have been reported.
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| Toxicity/Toxicokinetics |
In preclinical toxicity studies, GSK2983559 is generally well-tolerated at therapeutic doses (up to 30 mg/kg/day in rodents). No significant acute toxicity or mortality has been reported at these doses. The most common adverse effects associated with RIP2 inhibition, based on the target's role in innate immunity, may include increased susceptibility to bacterial infections (e.g., from gut microbiota), but this has not been extensively characterized for GSK2983559. In chronic toxicity studies (e.g., 28-day repeat-dose in rodents), no significant organ toxicity or changes in hematological/biochemical parameters (liver enzymes, creatinine, BUN) have been reported at doses up to 30 mg/kg/day. No genotoxicity or carcinogenicity data are publicly available. The compound is not intended for human use without regulatory approval; it is a research compound. As of 2026, GSK2983559 has not been approved by the FDA or any regulatory agency. The TFA salt form is not used for in vivo studies; the free acid or phosphate ester prodrug is typically studied. Standard laboratory safety precautions (gloves, lab coat, eye protection) should be used.
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| References |
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| Additional Infomation |
RIP2 (RIPK2, receptor-interacting serine/threonine-protein kinase 2) is a key mediator of the innate immune response downstream of nucleotide-binding oligomerization domain-containing proteins NOD1 and NOD2, which recognize bacterial peptidoglycan fragments. NOD2 mutations are associated with Crohn's disease and Blau syndrome, making RIP2 an attractive therapeutic target for inflammatory bowel disease (IBD). GSK2983559 (originally developed by GlaxoSmithKline) is a first-in-class RIP2 inhibitor that was advanced as a clinical candidate for IBD. The compound is a phosphate ester prodrug (GSK2983559) that releases the active free acid moiety. The chemical name of the active form is 2-((4-(benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl dihydrogen phosphate. GSK2983559 has demonstrated efficacy in pre-clinical models of colitis and shows excellent activity in human IBD explants. As of 2026, the clinical development status of GSK2983559 is not publicly confirmed; however, no RIP2 inhibitor has received regulatory approval to date. The compound remains a valuable research tool for studying NOD2-RIP2 signaling in innate immunity, inflammation, and autoimmunity. It is for research use only and is not approved for human therapy.
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| Molecular Formula |
C21H28CAN4O10PS2+
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| Molecular Weight |
611.61
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| Related CAS # |
GSK2983559 free acid;1579965-12-0;GSK2983559 active metabolite;1423186-80-4
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| Appearance |
Yellow to brown solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :~2 mg/mL (~3.27 mM)
DMSO :< 1 mg/mL DMF :< 1 mg/mL Ethanol :< 1 mg/mL |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6350 mL | 8.1751 mL | 16.3503 mL | |
| 5 mM | 0.3270 mL | 1.6350 mL | 3.2701 mL | |
| 10 mM | 0.1635 mL | 0.8175 mL | 1.6350 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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