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Purity: ≥98%
YKL-05-099 (YKL05099) is a novel, potent and selective inhibitor of salt-inducible kinase (SIK) with the potential to be used for treatment of inflammatory disorders. YKL-05-099 acts by binding to SIK1 and SIK3 with IC50s of ~10 and ~30 nM, respectively. YKL-05-099 has slightly less potent SIK2-inhibitory (IC50=40 nM). SIKs are promising therapeutic targets for modulating cytokine responses during innate immune activation.
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| ln Vitro |
The SIK2 inhibitory activity (IC50=40 nM) and IL-10 boosting activity (EC50=460 nM) of YKL-05-099 are marginally lower. YKL-05-099 bound to SIK1 and SIK3 with IC50s of 10 and 30 nM, respectively, in competitive binding tests. When bone marrow-derived macrophages were preincubated with YKL-05-099, the amount of HDAC5 phosphorylation at the SIK-specific phosphorylation site Ser259 was decreased in response to LPS stimulation. When BMDCs are stimulated with yeast cell wall extract Zymosan A, YKL-05-099 only slightly increases the release of IL-1β and suppresses the production of the inflammatory cytokines TNFα, IL-6, and IL-12p40 [1].
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| ln Vivo |
Under 10 μM, YKL-05-099 exhibits no toxicity and maintains its stability in mouse liver microsomes for more than two hours. YKL-05-099 exhibits strong solubility (PBS solubility = 428 μM) and can be found in mouse plasma at significant amounts in an unbound state. HDAC5 phosphorylation at the SIK regulatory site Ser259 is dose-dependently decreased by YKL-05-099; at the lowest dosage (5 mg/Kg), reduced phosphorylation was found, and at the start of the 20 mg/Kg dose detection limit, it was lower than Western blotting. At 5 mg/kg, YKL-05-099 dose-dependently lowers the amount of TNFα in serum; at 20 mg/kg, it more than doubles IL-10 levels [1].
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| References |
[1]. Sundberg TB, et al. Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo. ACS Chem Biol. 2016 Aug 19;11(8):2105-11
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| Molecular Formula |
C32H34CLN7O3
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| Molecular Weight |
600.1105
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| CAS # |
1936529-65-5
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| SMILES |
O=C1N(C2=NC=C(OC)C=C2)C3=NC(NC4=CC=C(C5CCN(C)CC5)C=C4OC)=NC=C3CN1C6=C(C)C=CC=C6Cl
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| InChi Key |
VQINULODWGEVBB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H34ClN7O3/c1-20-6-5-7-25(33)29(20)39-19-23-17-35-31(37-30(23)40(32(39)41)28-11-9-24(42-3)18-34-28)36-26-10-8-22(16-27(26)43-4)21-12-14-38(2)15-13-21/h5-11,16-18,21H,12-15,19H2,1-4H3,(H,35,36,37)
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| Chemical Name |
3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one
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| Synonyms |
YKL05099;YKL-05-099; YKL 05 099;
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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 : ≥ 75 mg/mL (~124.98 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume 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 (4.17 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension 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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6664 mL | 8.3318 mL | 16.6636 mL | |
| 5 mM | 0.3333 mL | 1.6664 mL | 3.3327 mL | |
| 10 mM | 0.1666 mL | 0.8332 mL | 1.6664 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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