| Size | Price | Stock | Qty |
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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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| 250mg |
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| Targets |
LH846 selectively targets Casein Kinase 1δ (CK1δ). CK1δ is a serine/threonine protein kinase that plays a critical role in the regulation of circadian rhythms by phosphorylating key clock proteins like PER1 and PER2. By inhibiting CK1δ, LH846 prevents the phosphorylation and subsequent degradation of PER1. This leads to an accumulation of PER1 protein, which lengthens the circadian period. The compound also inhibits CK1ε and CK1α, but with lower potency.
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| ln Vitro |
LH846 is a strong inhibitor of CKIδ, with an IC50 of 290 nM. It has no effect on CK2 and a modest inhibitory effect on CKIα and CKIε, with IC50 values of 2.5 μM and 1.3 μM, respectively. In HEK293T cells, LH846 (3 or 10 μM) suppresses the phosphorylation of PER1 in a CKIδ-dependent manner [1].
In vitro, LH846 demonstrates potent and selective inhibition of CK1δ with an IC50 of 290 nM. It inhibits CK1ε and CK1α at much higher concentrations, with IC50 values of 1.3 μM and 2.5 μM, respectively. It displays no inhibitory activity at CK2. In cellular assays, LH846 inhibits CK1δ-mediated phosphorylation and degradation of the PER1 protein in U2OS cells. This results in a lengthening of the circadian period, with minimal effect on amplitude. |
| ln Vivo |
In vivo, LH846's activity has been demonstrated in cellular models that express circadian rhythms. By lengthening the circadian period in U2OS cells, it provides a direct measure of its functional activity. Its ability to modulate circadian rhythms suggests potential for in vivo applications, such as in the treatment of circadian rhythm disorders, though detailed in vivo studies are not provided in the search results.
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| Enzyme Assay |
Non-cell-based enzyme assays for LH846 typically involve the use of purified CK1δ enzyme. The enzyme is incubated with a peptide substrate and ATP in a buffer system. LH846 is added at various concentrations, and the kinase activity is measured by quantifying the phosphorylation of the substrate. This can be done using radiometric methods (e.g., [γ-33P]-ATP incorporation) or by using fluorescence-based or luminescence-based assays. An IC50 value is determined from a dose-response curve.
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| Cell Assay |
Cellular assays for LH846 are performed using U2OS cells that have been engineered to express a circadian reporter, such as a luciferase gene driven by a circadian promoter. The cells are treated with LH846, and the bioluminescence is recorded over several days to monitor the circadian rhythm. The period length and amplitude of the rhythm are analyzed. This assay provides a direct measure of the compound's functional effect on the cellular circadian clock.
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| Animal Protocol |
In vivo animal models for LH846 would likely involve studies in mice to assess its effect on circadian behavior. The compound could be administered, and the animals' activity rhythms would be monitored using running wheels or other activity monitors. The effect of the compound on the period length of the activity rhythm would be measured. These studies are important for understanding the compound's potential therapeutic applications in circadian rhythm disorders. Detailed protocols are not provided in the search results.
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| ADME/Pharmacokinetics |
LH846 has a molecular weight of 316.81 g/mol and a molecular formula of C16H13ClN2OS. It is a cell-permeable compound. It is soluble in DMSO. Detailed PK parameters such as half-life and bioavailability are not extensively detailed in the provided search results. It is typically stored as a powder at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for LH846 are not provided in the search results. As a kinase inhibitor, its safety profile would be a key consideration. Off-target effects on other kinases could lead to toxicity. The compound is intended for research use only and is not for human consumption.
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| References | |
| Additional Infomation |
LH846 is a selective inhibitor of casein kinase 1δ (CK1δ). It has IC50 values of 290 nM, 1.3 μM, and 2.5 μM for CK1δ, CK1ε, and CK1α, respectively, and displays no activity at CK2. It inhibits CK1δ-mediated phosphorylation and degradation of PER1, lengthening the circadian period in U2OS cells. It is a benzothiazole analog with the CAS number 639052-78-1 and is supplied for research purposes.
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| Molecular Formula |
C16H13CLN2OS
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| Molecular Weight |
316.803
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| Exact Mass |
316.043
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| CAS # |
639052-78-1
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| PubChem CID |
851474
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| Appearance |
Pale purple to purple solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.709
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| LogP |
4.67
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
375
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| Defined Atom Stereocenter Count |
0
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| Synonyms |
LH 846 LH-846 LH846
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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 : ≥ 45 mg/mL (~142.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.89 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 | 3.1566 mL | 15.7828 mL | 31.5657 mL | |
| 5 mM | 0.6313 mL | 3.1566 mL | 6.3131 mL | |
| 10 mM | 0.3157 mL | 1.5783 mL | 3.1566 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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