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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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WEHI-345 (WEHI345) is a novel, potent and selective RIPK2 inhibitor with therapeutic potential to treat NOD-driven inflammatory diseases. With an IC50 of 0.13 M, it inhibits RIPK2, exhibits NOD signaling events, and stops the production of pro-inflammatory cytokines. By recognizing antigens, such as bacterial peptidoglycans, intracellular nucleotide binding and oligomerization domain (NOD) receptors start immune responses by inducing the production of pro-inflammatory cytokines by activating NF-B and MAP kinases. For NOD-mediated NF-κB activation and cytokine production, receptor interacting protein kinase 2 (RIPK2) is essential. Following NOD activation, WEHI-345 postpones the ubiquitylation of RIPK2 and the activation of NF-B. Even though WEHI-345 only delays NF-B activation in response to NOD stimulation, it prevents cytokine production both in vitro and in vivo and lessens experimental autoimmune encephalomyelitis in mice.
| Targets |
RIPK2 kinase (IC50 = 0.13 μM)
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|---|---|
| ln Vitro |
In cells, MDP-induced RIPK2 autophosphorylation activity can be inhibited by WEHI-345 (500 nM; Raw 267.4 cells) [1]. In bone marrow, MDP-induced transcription of the inflammatory mediators TNF and interleukin 6 (IL-6) is efficiently blocked by WEHI-345 (500 nM; 0 hours, 2 hours, 4 hours, and 8 hours; BMDM or THP-1 cells). ..derived macrophages (BMDM). WEHI-345 lowers the mRNA levels of NF-kB targets in THP-1 cells, including TNF, IL-8, IL-1b, and A20 [1].
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| ln Vivo |
WEHI-345 (20 mg/kg; i.p.; twice daily; for 6 days; male C57BL/6 mice) treatment decreased histology scores, disease scores, inflammatory infiltrates, and the recruitment of dendritic cells to inflammatory areas. It increased body weight as well as decreased levels of cytokines and chemokines, suggesting a general improvement in wild-type C57Bl/6 mice provoked with experimental autoimmune encephalomyelitis (EAE) [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Original 267.4 Cell Tested Concentrations: 500 nM Incubation Duration: Experimental Results: Inhibition of MDP-induced RIPK2 autophosphorylation activity in cells. RT-PCR[1] Cell Types: BMDM or THP-1 Cell Tested Concentrations: 500 nM Incubation Duration: 0 hrs (hours), 2 hrs (hours), 4 hrs (hours), 8 hrs (hours) Experimental Results: Blocks the transcription of MDP-induced inflammatory mediators TNF and interleukin 6 (IL-6) in BMDM. and diminished the mRNA levels of NF-kB targets in THP-1 cells. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 male mice (8 weeks old) [1]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection; twice (two times) daily; for 6 days Experimental Results: disease score, inflammatory infiltrate, histological score, and inflammation diminished dendritic cell recruitment to the site. and improved body weight and diminished cytokine and chemokine levels. |
| References |
| Molecular Formula |
C22H23N7O
|
|---|---|
| Molecular Weight |
401.464323282242
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| Exact Mass |
401.196
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| Elemental Analysis |
C, 65.82; H, 5.77; N, 24.42; O, 3.99
|
| CAS # |
1354825-58-3
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| Related CAS # |
1354825-58-3
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| PubChem CID |
56602554
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
709.0±60.0 °C at 760 mmHg
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| Flash Point |
382.6±32.9 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.687
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| LogP |
2.12
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
30
|
| Complexity |
586
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C1=CC=NC=C1)NCC(C)(N2N=C(C3=CC=C(C)C=C3)C4=C(N)N=CN=C42)C
|
| InChi Key |
LEBSTCDZKUSVOY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N7O/c1-14-4-6-15(7-5-14)18-17-19(23)26-13-27-20(17)29(28-18)22(2,3)12-25-21(30)16-8-10-24-11-9-16/h4-11,13H,12H2,1-3H3,(H,25,30)(H2,23,26,27)
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| Chemical Name |
N-[2-[4-amino-3-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-2-methylpropyl]pyridine-4-carboxamide
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| Synonyms |
WEHI 345; WEHI-345; WEHI345
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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 |
| 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) |
DMSO: ~25 mg/mL (~62.3 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4909 mL | 12.4545 mL | 24.9091 mL | |
| 5 mM | 0.4982 mL | 2.4909 mL | 4.9818 mL | |
| 10 mM | 0.2491 mL | 1.2455 mL | 2.4909 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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