Centrinone (LCR263; LCR-263; LCR 263) is a novel and potent inhibitor of polo-like kinase 4 (PLK4) with potential antineoplastic activity. It exhibits >1000-fold selectivity for PLK4 over Aurora A and Aurora B and inhibits PLK4 with a Ki of 0.16 nM.
Physicochemical Properties
| 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) |
Biological Activity
| Targets | PLK4 (Ki = 0.16 nM); PLK4 (G95L) (Ki = 68.57 nM); Aurora A (Ki = 171 nM); Aurora B (Ki = 436.76 nM) |
| ln Vitro | Centrinone (LCR-263) inhibits Plk4 to stop centriole assembly.In human and other vertebrate cells, centrinone treatment results in centrosome depletion. |
| 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. |
| 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. |
| References |
[1]. Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science. 2015 Jun 5;348(6239):1155-60. |
Solubility Data
| 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 |