| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
SIK1 2.0 nM (IC50) SIK2 0.7 nM (IC50) SIK3 0.6 nM (IC50)
GLPG3312 targets the salt-inducible kinases (SIK1, SIK2, and SIK3), which are members of the AMPK-related kinase family. These kinases play important roles in regulating inflammatory responses and immune cell function. By inhibiting SIKs, GLPG3312 modulates the production of cytokines such as TNFα and IL-10. |
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| ln Vitro |
In vitro, GLPG3312 potently inhibits TNFα release in LPS-stimulated human primary CD14+ monocytes and monocyte-derived macrophages (MdMs) with IC50 values of 17 nM and 34 nM, respectively. Conversely, at 20 μM, it increases IL-10 secretion by 14.8-fold in monocytes and 2.8-fold in MdMs. The compound shows excellent selectivity for SIKs over other kinases.
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| ln Vivo |
In vivo, oral administration of GLPG3312 in Balb/c mice at doses of 0.3, 1, or 3 mg/kg, followed by LPS challenge, results in dose-dependent inhibition of TNFα (27.0%, 57.2%, 77.5% inhibition, respectively) and increases in IL-10 levels (1.3, 2.4, and 3.1-fold, respectively). These results confirm its potent anti-inflammatory and immunomodulatory activity in vivo.
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| Enzyme Assay |
In vitro enzyme assays for GLPG3312 typically involve measuring its inhibitory activity against recombinant SIK1, SIK2, and SIK3 enzymes. These are cell-free kinase activity assays using appropriate peptide substrates and ATP, with IC50 values determined from dose-response curves. Selectivity profiling against a panel of other kinases is also performed to confirm its specificity for the SIK family.
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| Cell Assay |
In vitro cell-based studies use human primary CD14+ monocytes and monocyte-derived macrophages (MdMs) stimulated with LPS (100 ng/mL). Cells are pre-incubated with GLPG3312 for 1 hour before LPS stimulation. Cytokine levels (TNFα and IL-10) in the supernatant are measured by ELISA at specific time points (4 hours for monocytes, and 2 and 20 hours for MdMs for IL-10 and TNFα, respectively).
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| Animal Protocol |
In vivo studies are conducted in Balb/c mice. GLPG3312 is administered orally (p.o.) at doses of 0.3, 1, or 3 mg/kg. Fifteen minutes later, LPS (100 μg) is injected intraperitoneally (i.p.). Plasma cytokines are measured 1.5 hours after LPS treatment. This model is used to evaluate the compound's anti-inflammatory efficacy in vivo.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in animals show that GLPG3312 has good oral bioavailability: 60% in mice, 41.4% in rats (at 5 mg/kg), and 30% in dogs (at 30 mg/kg). These favorable PK properties support its use in oral dosing regimens for in vivo efficacy studies. Detailed PK parameters such as half-life and clearance are available from the manufacturer.
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| Toxicity/Toxicokinetics |
The toxicological profile of GLPG3312 has been evaluated in preclinical studies. It is considered to have a good safety margin based on its selectivity for SIKs. Specific toxicity data, such as NOAEL (No Observed Adverse Effect Level), are available from the supplier and can be provided upon request for research purposes.
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| References | |
| Additional Infomation |
Additional information: GLPG3312 (CAS 2340388-72-7) has a molecular formula of C23H21F2N5O3 and a molecular weight of 453.44. It is a research compound with a purity of 95% or higher, available from various chemical suppliers. It is not approved for clinical use and is intended for research purposes only, particularly in the study of inflammatory and immune diseases.
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| CAS # |
2340388-72-7
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|---|---|
| Appearance |
White to off-white solid powder
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| Density |
1.46±0.1 g/cm3(Predicted)
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| LogP |
0
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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 :~100 mg/mL (~220.54 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.51 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication.
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 and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.51 mM) 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; with ultrasonication. 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 and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. 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. View More
Solubility in Formulation 3: 2.5 mg/mL (5.51 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. |
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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