| Name | Longdaysin |
| Description | Longdaysin is an inhibitor of CK1α and CK1δ (IC50s: 5.6/8.8 μM). It also can inhibit ERK2 (IC50: 52 μM). |
| Cell Research | 2×10^5 cells were suspended in 100 μL serum-free medium containing the indicated concentrations of longdaysin, and then seeded in 24-transwell chambers with 8 μm pore membrane. The lower chamber contained medium with 20% FBS. After incubation at 37°C for 6 hours, the unmigrated cells on the upper side of membrane were removed by a cotton swab, and the migrated cells were stained with crystal violet and stained cells were photomicrographed. For invasion assays, the transwell chambers with 8 μm pore membranes were coated with Matrigel [2]. |
| Kinase Assay | The CKIδ, CKIα, CDK7, and ERK2 kinase assays were performed on 384-well plates (10 μl volume). The reaction mixture was as follows: for CKIδ, 2 ng/μl CKIδ, 50 μM peptide substrate RKKKAEpSVASLTSQCSYSS corresponding to human PER2 Lys659-Ser674, and CKI buffer (40 mM Tris, 10 mM MgCl2, 0.5 mM DTT, 0.1 mg/ml BSA, pH 7.5); for CKIα, 1 ng/μl CKIα, 50 μM CKI peptide substrate, and CKI buffer; for CDK7, 5 ng/μl CDK7, 100 μM Cdk7/9 peptide substrate, and CKI buffer; for ERK2, 1.5 ng/μl ERK2, 0.8 μg/μl MBP, and ERK buffer (50 mM Tris, 10 mM MgCl2, 0.5 mM DTT, 1 mM EGTA, pH 7.5). Five hundred nl of compound was added to the mixture (final 5% DMSO), and the reaction was started by adding ATP (final 5 μM). After incubation at 30°C for 3h, 10 μl of Kinase-Glo Luminescent Kinase Assay reagent was added, and the luminescence was detected to determine the remaining ATP amount. All of the tested compounds did not inhibit luciferase activity directly [1]. |
| Animal Research | MDA-MB-231 cells were injected s.c. into the right flank of nude mice (1×10^7 cells per mouse), and tumor growth was closely observed and measured every 3 days. When the tumors reached approximately 50 mm3, the mice were randomly divided into two groups (eight mice per group) and i.p. injected with the vehicle (0.8% DMSO/12% Cremophor/8% ethanol in normal saline) or 5 mg/kg longdaysin in vehicle every 3 days. This longdaysin dosage was selected based on results from preliminary experiments, and was well tolerated in the mouse model. Subsequently, tumor volumes were measured with a caliper and calculated as follows: 0.523×(length)×(width)2. After treatment for 3 weeks, the mice were sacrificed and the tumor tissues were collected and weighed before being fixed in buffered formalin [2]. |
| In vitro | Longdaysin inhibited CKIδ, CKIα, ERK2, and CDK7 activities (IC50?=?8.8, 5.6, 52, and 29 μM, respectively), while it had much less effect on p38α. The period of CKIδ deficient cells was 1.1 h longer than that of wild type cells. Longdaysin lengthened the period in a dose-dependent manner in CKIδ deficient cells as well as in wild type cells [1]. In breast cancer Hs578T and MDA-MB-231 cells, micromolar concentrations of longdaysin attenuated the phosphorylation of LRP6 and DVL2 and reduced the expression of active β-catenin and total β-catenin, leading to the downregulation of Wnt target genes Axin2, DKK1, LEF1, and Survivin [2]. |
| In vivo | In MDA-MB-231 breast cancer xenografts, treatment with longdaysin suppressed tumor growth in association with inhibition of Wnt/β-catenin signaling [2]. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 100 mg/mL (298.21 mM), Sonication is recommended.
H2O : Insoluble
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| Keywords | Longdaysin | Inhibitor | inhibit | Extracellular signal regulated kinases | ERK2 | ERK | Cyclin dependent kinase | CKIδ | CKIα | CDK7 | CDK | CaseinKinase | Casein Kinase |
| Inhibitors Related | TBHQ | Ribociclib | Notoginsenoside R1 | Lidocaine | Astragaloside IV | Abemaciclib | Lidocaine hydrochloride | Honokiol | Tauroursodeoxycholate | CASIN | Nisin Z | Dinaciclib |
| Related Compound Libraries | Anti-Pancreatic Cancer Compound Library | Pain-Related Compound Library | Bioactive Compound Library | Membrane Protein-targeted Compound Library | HIF-1 Signaling Pathway Compound Library | Kinase Inhibitor Library | Inhibitor Library | Immunology/Inflammation Compound Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Liver Cancer Compound Library | Anti-Cancer Active Compound Library |
United States