| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
PLK4 (Ki = 0.59 nM); PLK4 (G95L) (Ki = 497.53 nM); Aurora A (Ki = 1239 nM); Aurora B (Ki = 5597.14 nM)
PLK4 (polo-like kinase 4). Centrinone-B inhibits PLK4 with a Ki of 0.59 nM. It shows weak binding to Aurora A (Ki = 1239 nM) and Aurora B (Ki = 5597.14 nM), demonstrating >1000-fold selectivity for PLK4 over these kinases. It also inhibits the G95L mutant of PLK4 with a Ki of 497.53 nM. Centrinone-B exhibits >1000-fold selectivity for PLK4 over Aurora A/B in vitro. The high selectivity of Centrinone-B for PLK4 makes it a valuable tool for studying the specific functions of this kinase without off-target effects on Aurora A or B. |
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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].
Centrinone-B exhibits >1000-fold selectivity for PLK4 over Aurora A/B in vitro and does not affect cellular Aurora A or B substrate phosphorylation at concentrations that deplete centrosomes. It significantly decreases the cell viability of PLK4-centriole conjunction melanoma cell lines (except p53 mutant SK-MEL-28). Inhibition of PLK4 by Centrinone-B induces apoptosis in human melanoma cell lines. Centrinone-B has demonstrated activity in cellular assays and is a key tool for investigating centriole duplication and potential therapeutic strategies, such as in triple-negative breast cancer models. The compound can reduce centrosomes without affecting Aurora A/B, and it induces apoptosis in most melanoma cell lines. |
| 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].
In vivo activity data for Centrinone-B is limited. As a potent and highly selective PLK4 inhibitor, it is used to study the effects of PLK4 inhibition in animal models. Its in vivo effects are expected to be related to its mechanism of disrupting centriole assembly and inducing apoptosis in cancer cells. Centrinone-B has demonstrated activity in cellular assays and is a key tool for investigating centriole duplication and potential therapeutic strategies, such as in triple-negative breast cancer models. Animal models of cancer could be used to evaluate the antitumor efficacy of Centrinone-B. |
| Enzyme Assay |
Kinase assays are performed in white 384-well plates. Purified 6xHis-tagged human PLK4 kinase domain (aa 2-275) is used, expressed in E. coli and purified via Ni-NTA affinity chromatography. The kinase is stored in 20 mM Tris pH 7.5, 100 mM NaCl, 10% glycerol, 1 mM DTT. The assay involves mixing equal volumes of enzyme and substrate with inhibitors. The specific reaction buffer and detection method are not detailed in the provided text. The assay measures the inhibition of PLK4 enzymatic activity by Centrinone-B, allowing for the determination of IC50 and Ki values.
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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].
Cellular assays for Centrinone-B typically involve treating melanoma cell lines with the compound at concentrations ranging from 0-200 nM. Cell viability is then assessed to determine the antiproliferative effects. The compound's ability to induce apoptosis can also be evaluated in these cell lines. Centrinone-B has demonstrated activity in cellular assays and is a key tool for investigating centriole duplication and potential therapeutic strategies, such as in triple-negative breast cancer models. The compound can reduce centrosomes without affecting Aurora A/B, and it induces apoptosis in most melanoma cell lines. |
| Animal Protocol |
In vivo animal model experimental protocols for Centrinone-B are not detailed in the provided references. As a research compound, it would be administered to animal models, such as those with melanoma xenografts, to study its antitumor efficacy and pharmacodynamic effects. Centrinone-B has demonstrated activity in cellular assays and is a key tool for investigating centriole duplication and potential therapeutic strategies, such as in triple-negative breast cancer models.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Centrinone-B is not available in the provided references. As a small molecule inhibitor, its PK properties would typically be evaluated in preclinical studies involving administration to animal models to determine parameters like bioavailability, half-life, and clearance. The compound is a research tool and is not intended for clinical use.
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| Toxicity/Toxicokinetics |
Specific toxicological data for Centrinone-B is not available in the provided references. As a research compound, its safety profile would be evaluated in standard preclinical toxicology studies to determine potential adverse effects and establish a safe dose range for in vivo experiments. The compound is intended for research use only.
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| References | |
| Additional Infomation |
Centrinone-B is a research tool for studying the role of PLK4 in cancer and other diseases. It is not approved for clinical use. Its high selectivity for PLK4 makes it a valuable tool for dissecting the specific functions of this kinase. The compound is typically supplied as a light yellow to yellow solid powder. Centrinone-B has demonstrated activity in cellular assays and is a key tool for investigating centriole duplication and potential therapeutic strategies, such as in triple-negative breast cancer models.
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| Molecular Formula |
C27H27F2N7O5S2
|
|---|---|
| Molecular Weight |
631.67
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| Exact Mass |
631.148
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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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| PubChem CID |
118704753
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
904.9±75.0 °C at 760 mmHg
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| Flash Point |
501.1±37.1 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.687
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| LogP |
3.77
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
43
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| Complexity |
1030
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(=C(C=1)F)SC1=NC(=C(C(=N1)N1CCCCC1)OC)NC1C=C(C)NN=1)(CC1C=CC=C(C=1F)[N+](=O)[O-])(=O)=O
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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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