| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
PLK4 (Ki = 0.16 nM); PLK4 (G95L) (Ki = 68.57 nM); Aurora A (Ki = 171 nM); Aurora B (Ki = 436.76 nM)
PLK4 (polo-like kinase 4). Centrinone is a highly selective inhibitor of PLK4, with a Ki of 0.16 nM. It displays >1000-fold selectivity for PLK4 over Aurora A (Ki = 171 nM) and Aurora B (Ki = 436.76 nM). It also inhibits the G95L mutant of PLK4 with a Ki of 68.57 nM. Centrinone treatment causes centrosome depletion in human and other vertebrate cells. The high selectivity of Centrinone for PLK4 over other kinases makes it a valuable tool for dissecting the specific functions of PLK4 in centriole duplication and centrosome assembly, without off-target effects on Aurora A or B kinases. |
|---|---|
| ln Vitro |
Centrinone (LCR-263) inhibits Plk4 to stop centriole assembly.In human and other vertebrate cells, centrinone treatment results in centrosome depletion.
Centrinone inhibits PLK4 to halt centriole assembly, leading to centrosome depletion in human and other vertebrate cells. In human and other vertebrate cells, treatment with Centrinone results in centrosome depletion. It induces cell cycle arrest in normal human cell lines in a p53-dependent manner. At concentrations that deplete centrosomes, it does not affect cellular Aurora A or B substrate phosphorylation. In Ewing's sarcoma cells, Centrinone induces mitochondrial membrane depolarization, caspase 3/7 activation, PARP1 cleavage, and DNA fragmentation, indicating an apoptotic form of cell death. The compound is effective against Ewing's sarcoma cells in vitro, providing a rationale for its evaluation in vivo. |
| ln Vivo |
In vivo activity data for Centrinone is limited. As a potent and selective PLK4 inhibitor, it is primarily used as a research tool to study the biological consequences of centrosome loss in cells and organisms. Its in vivo effects are expected to relate to its mechanism of disrupting centriole assembly and centrosome function. Centrinone treatment causes centrosome depletion in human and other vertebrate cells. PLK4 inhibitors, including Centrinone, are effective against Ewing's sarcoma cells in vitro and thus provide a rationale for their evaluation in vivo. The compound's effects on centrosome depletion and cell cycle arrest could be studied in animal models to understand the role of PLK4 in development and disease.
|
| Enzyme Assay |
The human Plk4 kinase domain with 6xHis tag has been purified and is stored in 20 mM Tris pH 7.5, 100 mM NaCl, 10% glycerol, and 1 mM DTT. The contents of the 2X reaction buffer are as follows: 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. At a pH of 8.0, the final reaction contains 2.5–10 nM of Plk4. DMSO stocks are used to add inhibitors (Centrinone) that vary in dose response. Reactions are permitted to continue at 25°C for 4–16 hours. ADP-Glo reagent is used for detection. Plate readers are used to measure luminosity.
The human PLK4 kinase domain with a 6xHis tag is purified and stored in 20 mM Tris pH 7.5, 100 mM NaCl, 10% glycerol, and 1 mM DTT. The 2X reaction buffer consists of 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. The final reaction contains 2.5–10 nM of PLK4 at pH 8.0. Inhibitors are added from DMSO stocks in a dose-response manner. Reactions proceed at 25°C for 4–16 hours and are detected using ADP-Glo reagent. Luminescence is measured with a plate reader. The assay measures the inhibition of PLK4 enzymatic activity by Centrinone, allowing for the determination of IC50 and Ki values. |
| Cell Assay |
Cells are seeded at 50,000 cells/well in triplicate into 6-well plates for each condition. HeLa cells receive 125 nM Centrinone (LCR-263) addition, while NIH/3T3 cells receive 300 nM. Three wells are harvested for each condition every twenty-four hours. An automated cell counter called the TC10 is used to count cells.
Cells are seeded at 50,000 cells/well in triplicate into 6-well plates. HeLa cells are treated with 125 nM Centrinone, while NIH/3T3 cells receive 300 nM. Three wells are harvested for each condition every twenty-four hours. An automated cell counter (TC10) is used to count cells. The effect of Centrinone on cell proliferation and centrosome levels can be assessed. In Ewing's sarcoma cells, Centrinone treatment induces mitochondrial membrane depolarization, caspase 3/7 activation, PARP1 cleavage, and DNA fragmentation, indicating apoptosis. The compound's effects on cell cycle arrest and centrosome depletion can be evaluated using various cellular assays. |
| Animal Protocol |
In vivo animal model experimental protocols for Centrinone are not detailed in the provided references. As a research compound, it would typically be administered to animal models to study the effects of PLK4 inhibition and centrosome depletion on tumor growth or developmental processes. PLK4 inhibitors, including Centrinone, are effective against Ewing's sarcoma cells in vitro, providing a rationale for their evaluation in vivo. Animal models of cancer, such as xenograft models, could be used to evaluate the antitumor efficacy of Centrinone.
|
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Centrinone 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, so extensive PK data may not be available.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for Centrinone 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 and not for human consumption.
|
| References | |
| Additional Infomation |
Centrinone is a research tool for studying the role of PLK4 and centrosomes in cell division and cancer. It is not approved for clinical use. Its high selectivity for PLK4 makes it valuable for dissecting the specific functions of this kinase. The compound is typically supplied as a light yellow to yellow solid powder. Centrinone is structurally and functionally closely related to Centrinone-B, and both reversibly inhibit PLK4 with high potency. The compound is used in studies of centriole duplication, centrosome biology, and cell cycle control.
|
| Molecular Formula |
C26H25F2N7O6S2
|
|---|---|
| Molecular Weight |
633.65
|
| Exact Mass |
633.127
|
| Elemental Analysis |
C, 49.28; H, 3.98; F, 6.00; N, 15.47; O, 15.15; S, 10.12
|
| CAS # |
1798871-30-3
|
| Related CAS # |
Centrinone-B;1798871-31-4
|
| PubChem CID |
91801159
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.6±0.1 g/cm3
|
| Boiling Point |
924.2±75.0 °C at 760 mmHg
|
| Flash Point |
512.7±37.1 °C
|
| Vapour Pressure |
0.0±0.3 mmHg at 25°C
|
| Index of Refraction |
1.693
|
| LogP |
2.15
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
43
|
| Complexity |
1040
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1C=CC(=C(C=1)F)SC1=NC(=C(C(=N1)N1CCOCC1)OC)NC1C=C(C)NN=1)(CC1C=CC=C(C=1F)[N+](=O)[O-])(=O)=O
|
| InChi Key |
HHJSKDRCUMVWKF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H25F2N7O6S2/c1-15-12-21(33-32-15)29-24-23(40-2)25(34-8-10-41-11-9-34)31-26(30-24)42-20-7-6-17(13-18(20)27)43(38,39)14-16-4-3-5-19(22(16)28)35(36)37/h3-7,12-13H,8-11,14H2,1-2H3,(H2,29,30,31,32,33)
|
| Chemical Name |
2-[2-fluoro-4-[(2-fluoro-3-nitrophenyl)methylsulfonyl]phenyl]sulfanyl-5-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-ylpyrimidin-4-amine
|
| Synonyms |
LCR263; LCR 263; LCR-263; Centrinone
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ≥ 31 mg/mL (~48.9 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.95 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 | 1.5782 mL | 7.8908 mL | 15.7816 mL | |
| 5 mM | 0.3156 mL | 1.5782 mL | 3.1563 mL | |
| 10 mM | 0.1578 mL | 0.7891 mL | 1.5782 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.
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
