| 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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Centrinone-B (LCR323; LCR-323; LCR 323) is a novel and reversible polo-like kinase 4 (PLK4) inhibitor with potential anticancer activity. With a Ki of 0.59 nM, it exhibits >1500-fold selectivity in inhibiting PLK4 in comparison to Aurora A and Aurora B.
| Targets |
PLK4 (Ki = 0.59 nM); PLK4 (G95L) (Ki = 497.53 nM); Aurora A (Ki = 1239 nM); Aurora B (Ki = 5597.14 nM)
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| ln Vitro |
Centrinone-B (LCR-323) has a Ki of 0.59 nM and is a powerful and highly selective PLK4 inhibitor. With Kis of 1239 nM and 5597.14 nM, respectively, centrinone-B binds to Aurora A and Aurora B very weakly. In vitro, centrinone-B (LCR-323) shows >1000-fold selectivity for Plk4 over Aurora A/B, and at concentrations that deplete centrosomes, it has no effect on the phosphorylation of the Aurora A or B substrate in cells[1]. Through inhibition of PLK4, centrinone-B (LCR-323) (0-200 nM) dramatically reduces the viability of PLK4-centriole conjunction melanoma cell lines, with the exception of the p53 mutant SK-MEL-28. uman melanoma cell lines undergo apoptosis in response to Centrinone-B (LCR-323)-induced PLK4 inhibition[2].
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| ln Vivo |
In white 384-well plates, all kinase assays are conducted. Equal volumes of the following are used in Plk4 assays: (1) purified 6xHis-tagged human Plk4 kinase domain (aa 2-275), which was expressed in E. coli and purified using Ni-NTA affinity chromatography; (2) 2X reaction buffer comprising 50 mM HEPES pH 8.5, 20 mM MgCl2, 1 mM DTT, 0.2 mg/mL BSA, 16 μM ATP, and 200 μM A-A11 substrate (amino acid sequence: TPSDSLIYDDGLS). After the reaction is complete, the pH is 8.0 and the Plk4 concentration ranges from 2.5 to 10 nM. Stocks of DMSO are supplemented with inhibitors arranged according to dose response. At 25°C, reactions can last for four to sixteen hours. Using the ADP-Glo reagent, detection is accomplished. The Infinite M1000 plate reader is used to measure luminosity. Kis is determined from IC50 data and data are fitted using Prism[1].
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| Cell Assay |
The CytoTox-Glo assay is used to assess the impact of centrinone B on the viability of normal melanocytes and melanoma cell lines. In a nutshell, cells are counted, plated in a 96-well plate, and treated with centrinone B for 48 hours the following day. After that, the cells are incubated with AAF-Glo substrate (alanyl-alanylphenylalanyl-aminoluciferin) for 15 minutes, which gives rise to a luminescent signal that indicates a distinct intracellular protease activity linked to cytotoxicity (dead-cell protease). After adding digitonin to lyse the remaining viable cells, the luminescent signals of dead cells (caused by centrinone B) are subtracted from the total number of dead cells to determine the viability of the cells. Relative light units (RLU) for viable cells are used to represent data[2].
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| References |
| Molecular Formula |
C27H27F2N7O5S2
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|---|---|
| Molecular Weight |
631.67
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| Exact Mass |
631.1483
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| Elemental Analysis |
C, 51.34; H, 4.31; F, 6.02; N, 15.52; O, 12.66; S, 10.15
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| CAS # |
1798871-31-4
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| Related CAS # |
Centrinone;1798871-30-3
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| Appearance |
Solid powder
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| SMILES |
CC1=CC(=NN1)NC2=C(C(=NC(=N2)SC3=C(C=C(C=C3)S(=O)(=O)CC4=C(C(=CC=C4)[N+](=O)[O-])F)F)N5CCCCC5)OC
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| InChi Key |
UPZNTUYHCRQOIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H27F2N7O5S2/c1-16-13-22(34-33-16)30-25-24(41-2)26(35-11-4-3-5-12-35)32-27(31-25)42-21-10-9-18(14-19(21)28)43(39,40)15-17-7-6-8-20(23(17)29)36(37)38/h6-10,13-14H,3-5,11-12,15H2,1-2H3,(H2,30,31,32,33,34)
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| Chemical Name |
2-[2-fluoro-4-[(2-fluoro-3-nitrophenyl)methylsulfonyl]phenyl]sulfanyl-5-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-6-piperidin-1-ylpyrimidin-4-amine
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| Synonyms |
LCR-323; CentrinoneB; LCR 323; Centrinone B; LCR323; Centrinone-B
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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: ~25 mg/mL (~39.6 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (3.96 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 sonication.
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. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.96 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 | 1.5831 mL | 7.9155 mL | 15.8311 mL | |
| 5 mM | 0.3166 mL | 1.5831 mL | 3.1662 mL | |
| 10 mM | 0.1583 mL | 0.7916 mL | 1.5831 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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