GSK2983559 free acid (compound 3) is a potent, specific and oral bioactive receptor interacting protein 2 (RIP2) kinase inhibitor, showing excellent activity in blocking many proinflammatory cytokine responses in vivo and in human inflammatory bowel disease explant samples.
Physicochemical Properties
| Molecular Formula | C21H23N4O7PS2 |
| Molecular Weight | 538.5298 |
| Exact Mass | 538.074 |
| Elemental Analysis | C, 46.84; H, 4.31; N, 10.40; O, 20.80; P, 5.75; S, 11.91 |
| CAS # | 1579965-12-0 |
| Related CAS # | GSK2983559;GSK2983559 active metabolite;1423186-80-4 |
| PubChem CID | 73386708 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 823.6±75.0 °C at 760 mmHg |
| Flash Point | 451.9±37.1 °C |
| Vapour Pressure | 0.0±3.1 mmHg at 25°C |
| Index of Refraction | 1.675 |
| LogP | 0.55 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 35 |
| Complexity | 878 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1=CC2=C(N=CN=C2C=C1OCCOP(=O)(O)O)NC1C=CC2=C(C=1)N=CS2)(C(C)(C)C)(=O)=O |
| InChi Key | MJLYDVMFNHZMLV-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H23N4O7PS2/c1-21(2,3)35(29,30)19-9-14-15(10-17(19)31-6-7-32-33(26,27)28)22-11-23-20(14)25-13-4-5-18-16(8-13)24-12-34-18/h4-5,8-12H,6-7H2,1-3H3,(H,22,23,25)(H2,26,27,28) |
| Chemical Name | 2-[4-(1,3-benzothiazol-5-ylamino)-6-tert-butylsulfonylquinazolin-7-yl]oxyethyl dihydrogen phosphate |
| Synonyms | GSK2983559; GSK-2983559; GSK 2983559; GSK2983559 free acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | RIP2 kinase |
| ln Vitro | GSK2983559 was found to be extremely selective in a screen against nonkinase targets (Eurofins, 104 receptor and ion channel binding assays, 35 enzyme and cell-based assays), inhibiting only the melatonin receptor MT3 at a concentration under 10 μM.[1]. |
| ln Vivo | GSK2983559 (oral gavage; 3 and 10 mg/kg; once) substantially suppresses MDP-induced IL-6 in mice [2]. |
| Enzyme Assay | In a murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model, administration of GSK2983559 at the 7.5 and 145 mg/kg b.i.d doses displays efficacy similar to that of prednisolone as measured by the sum of colon scores.[1]. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice (female) were injected with MDP (100 μg) [2] Doses: 3 and 10 mg/kg Route of Administration: po (oral gavage); 3 and 10 mg/kg; Experimental Results: in a dose-dependent manner Suppresses serum IL-6 levels. |
| References |
[1]. Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl Dihydrogen Phosphate, for the Treatment of Inflammat. [2]. Design, synthesis, and structure-activity relationship of novel RIPK2 inhibitors. Bioorg Med Chem Lett. 2022 Sep 2;75:128968. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~5 mg/mL (~9.3 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8569 mL | 9.2845 mL | 18.5691 mL | |
| 5 mM | 0.3714 mL | 1.8569 mL | 3.7138 mL | |
| 10 mM | 0.1857 mL | 0.9285 mL | 1.8569 mL |