WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 531198
CAS#: 639052-78-1
Description: LH846 is a selective inhibitor of casein kinase. IC50 values of LH846 are 290 nM, 1.3 μM and 2.5 μM for CK1δ, ε and α). LH 846 has been shown to inhibit CK1δ-dependent phosphorylation and degradation of PER1 protein and to lengthen the circadian period in U2OS cells.
MedKoo Cat#: 531198
Name: LH846
CAS#: 639052-78-1
Chemical Formula: C16H13ClN2OS
Exact Mass: 316.0437
Molecular Weight: 316.803
Elemental Analysis: C, 60.66; H, 4.14; Cl, 11.19; N, 8.84; O, 5.05; S, 10.12
Synonym: LH846; LH-846; LH 846.
IUPAC/Chemical Name: N-(5-Chloro-6-methyl-2-benzothiazolyl)benzeneacetamide
InChi Key: DYHAMRNAHTWYKY-UHFFFAOYSA-N
InChi Code: InChI=1S/C16H13ClN2OS/c1-10-7-14-13(9-12(10)17)18-16(21-14)19-15(20)8-11-5-3-2-4-6-11/h2-7,9H,8H2,1H3,(H,18,19,20)
SMILES Code: O=C(NC1=NC2=CC(Cl)=C(C)C=C2S1)CC3=CC=CC=C3
Appearance: Yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | LH846 is a selective inhibitor of CKIδ, with an IC50 of 290 nM, and less potently inhibits CKIα and CKIε, with IC50s of 2.5 μM and 1.3 μM, respectively. |
| In vitro activity: | A high-throughput cell-based screen identified a benzothiazole analogue, LH846, which induces period lengthening of the circadian rhythm. Affinity chromatography coupled with mass spectrometry and genomic analysis identified protein kinase CKIδ as the biological target of LH846. The benzothiazole derivative LH846 (8 μM) lengthened the period (10 h) with minimal effect on the amplitude of both Per2-dLuc and Bmal1-dLuc rhythms in U2OS cells (Figure 1). In vitro kinase profiling against a panel of around 50 kinases revealed that LH846 strongly inhibited CKIδ and, with less potency CKIα and ROCK2 (see Table 2S in the Supporting Information). Determination of the half maximal inhibitory concentration (IC50) based on an in vitro assay revealed that LH846 inhibited CKIδ with an IC50 of 290 nM, CKIα with an IC50 of 2.5 μM, CKIε with an IC50 of 1.3 μM and had no effect on CK2 (see Figure 1S in the Supporting Information). Taken together, these results suggest that CKIδ is the biological target of LH846. Reference: Angew Chem Int Ed Engl. 2011 Nov 4; 50(45): 10608–10611. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755734/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 38.0 | 119.95 |
The following data is based on the product molecular weight 316.803 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Lee JW, Hirota T, Peters EC, Garcia M, Gonzalez R, Cho CY, Wu X, Schultz PG, Kay SA. A small molecule modulates circadian rhythms through phosphorylation of the period protein. Angew Chem Int Ed Engl. 2011 Nov 4;50(45):10608-11. doi: 10.1002/anie.201103915. Epub 2011 Sep 26. PMID: 21954091; PMCID: PMC3755734. |
| In vitro protocol: | 1. Lee JW, Hirota T, Peters EC, Garcia M, Gonzalez R, Cho CY, Wu X, Schultz PG, Kay SA. A small molecule modulates circadian rhythms through phosphorylation of the period protein. Angew Chem Int Ed Engl. 2011 Nov 4;50(45):10608-11. doi: 10.1002/anie.201103915. Epub 2011 Sep 26. PMID: 21954091; PMCID: PMC3755734. |
| In vivo protocol: | TBD |
1: Lee JW, Hirota T, Peters EC, Garcia M, Gonzalez R, Cho CY, Wu X, Schultz PG,
Kay SA. A small molecule modulates circadian rhythms through phosphorylation of
the period protein. Angew Chem Int Ed Engl. 2011 Nov 4;50(45):10608-11. doi:
10.1002/anie.201103915. PubMed PMID: 21954091; PubMed Central PMCID: PMC3755734.
Unlike the great majority of protein kinases, which are tightly regulated enzymes, CK2 is endowed with high constitutive activity, a feature that is suspected to underlie its oncogenic potential and possible implication in viral infections. This makes CK2 an attractive target for anti-neoplastic and antiviral drugs.
