 Chemical Structure.png)
CFI400945 is a potent, selective, and orally bioavailable PLK4 (polo-like kinase 4) inhibitor with IC50 value of 2.8 ±1.4 nM and potential antineoplastic activity. CFI-400945 selectively inhibits PLK4, causing apoptosis to be induced and mitosis to be disrupted. Inhibition of PLK4 also stops PLK4-overexpressing tumor cells from proliferating and dividing. Breast cell line and other tumor cell line growth can be markedly inhibited by CFI-400945. PLK4 is specifically inhibited in cells by CFI-400945, but it also exhibits some activity against AURKB, TRKA, TRKB, and Tie2/TEK (of 290 kinases, only 10 demonstrated more than 50% inhibition).
Physicochemical Properties
| Molecular Formula | C33H34N4O3 | |
| Molecular Weight | 534.65 | |
| Exact Mass | 534.263 | |
| CAS # | 1338806-73-7 | |
| Related CAS # |
|
|
| PubChem CID | 58486178 | |
| Appearance | White to yellow solid powder | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 751.5±60.0 °C at 760 mmHg | |
| Flash Point | 408.3±32.9 °C | |
| Vapour Pressure | 0.0±2.5 mmHg at 25°C | |
| Index of Refraction | 1.698 | |
| LogP | 5.4 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 5 | |
| Rotatable Bond Count | 6 | |
| Heavy Atom Count | 40 | |
| Complexity | 942 | |
| Defined Atom Stereocenter Count | 4 | |
| SMILES | C[C@@H]1CN(C[C@@H](O1)C)CC2=CC=C(C=C2)/C=C/C3=NNC4=C3C=CC(=C4)[C@@H]5C[C@]56C7=C(C=CC(=C7)OC)NC6=O |
|
| InChi Key | DADASRPKWOGKCU-FVTQAUBDSA-N | |
| InChi Code | InChI=1S/C33H34N4O3/c1-20-17-37(18-21(2)40-20)19-23-6-4-22(5-7-23)8-12-29-26-11-9-24(14-31(26)36-35-29)28-16-33(28)27-15-25(39-3)10-13-30(27)34-32(33)38/h4-15,20-21,28H,16-19H2,1-3H3,(H,34,38)(H,35,36)/b12-8+/t20-,21+,28-,33-/m0/s1 | |
| Chemical Name | (2'S,3R)-2'-[3-[(E)-2-[4-[[(2R,6S)-2,6-dimethylmorpholin-4-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1'-cyclopropane]-2-one | |
| Synonyms |
|
|
| 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 (IC50 = 0.45 nM) | |
| ln Vitro | UF010 primarily inhibits the G1/S transition with an increased G1 cell population and a decreased cell population in the S phase in a dose-dependent manner in cell-cycle analysis using MDA-MB-231 cells. In cell culture medium containing 10% fetal bovine serum, UF010 has a half-life of 15.8 hours[1]. | |
| ln Vivo |
|
|
| Enzyme Assay | Using an indirect ELISA detection system, active PLK4 is purified and used to measure PLK4 activity. FRET-based homogeneous assay kits from Invitrogen are used to measure the compound inhibition of PLK1, PLK2, PLK3, AURKA, and AUKB/INCENP. ATP concentrations of 25, 60, and 80 μM are used for PLK1, PLK2, and PLK3, and 20 and 128 μM are used for AURKA and AURKB/INCENP, respectively, in the assays. | |
| Cell Assay | For six hours, HCT116 and A549 cells are exposed to either DMSO or etoposide (10 μM). One hour prior to cell lysis, TSA (0.2 μM), MS-275, and UF010 (2 μM) are added. Western blotting is performed on the whole cell lysates using antibodies to the specified proteins. It is found that PCNA is a loading control. | |
| Animal Protocol |
Adult female athymic CD1 nude mice 10 mg/kg via oral gavage |
|
| References |
[1]. The discovery of Polo-like kinase 4 inhibitors: identification of (1R,2S).2-(3-((E).4-(((cis).2,6-dimethylmorpholino)methyl)styryl). 1H.indazol-6-yl)-5?'-methoxyspiro[cyclopropane-1,3?'-indolin]-2?'-one (CFI-400945) as a potent, orally active antitumor agent. J Med Chem. 2015 Jan 8;58(1):147-69. [2]. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell. 2014 Aug 11;26(2):163-76. |
|
| Additional Infomation | Ocifisertib is a polo-like kinase 4 (PLK4) inhibitor with potential antineoplastic activity. Upon administration, ocifisertib selectively inhibits PLK4, which results in the disruption of mitosis and the induction of apoptosis. PLK4 inhibition also prevents cell division and inhibits proliferation of PLK4-overexpressing tumor cells. PLK4, a member of the polo family of serine/threonine kinases overexpressed in a variety of cancer cell types, plays a crucial role in the regulation of centriole duplication during the cell cycle. |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8704 mL | 9.3519 mL | 18.7038 mL | |
| 5 mM | 0.3741 mL | 1.8704 mL | 3.7408 mL | |
| 10 mM | 0.1870 mL | 0.9352 mL | 1.8704 mL |