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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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SKU | Size | Availability | Price | Qty |
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C413779-1mg | 1mg | In stock | $89.90 | |
C413779-5mg | 5mg | In stock | $312.90 | |
C413779-10mg | 10mg | In stock | $480.90 | |
C413779-25mg | 25mg | In stock | $1,167.90 | |
C413779-50mg | 50mg | In stock | $1,974.90 | |
C413779-100mg | 100mg | In stock | $2,963.90 |
PLK Inhibitors
Synonyms | CFI-400945 free base|CFI-400945|1338806-73-7|ocifisertib|TL1UD860AA|CFI-400945 (free base)|UNII-TL1UD860AA|1616420-30-4|(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'-cyc |
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Specifications & Purity | 97% |
Storage Temp | Store at -20°C |
Shipped In | Ice chest + Ice pads |
Grade | Moligand™ |
Action Type | INHIBITOR |
Mechanism of action | Inhibitor of polo like kinase 4 |
Product Description | Information CFI-400945 CFI-400945 is an orally active, potent and selective polo-like kinase 4(PLK4) inhibitor with Ki value of 0.26 nM. Targets PLK4 (Cell-free assay); TrkA (Cell-free assay); TrkB (Cell-free assay); Tie-2 (Cell-free assay); Aurora B (Cell-free assay) 16539,2.8 nM; 6 n In vitro CFI-400945 is a potent, orally active antitumor agent with the IC50 and Ki values of 2.8 and 0.26 nM, respectively. No significant inhibition against PLKs 1-3 is observed for CFI-400945 at a concentration of 50 μM. CFI-400945 can attenuate the growth of breast cell line, as well as other tumor cell lines significantly. CFI-400945 selectively inhibits PLK4 in cells, but also has certain activity against AURKB, TRKA, TRKB and Tie2/TEK (only 10 kinases showed more than 50% inhibition among 290 kinases). The cytokinesis failure and subsequent polyploidization by CFI-400945 treatment indicate that the cell death in cancer cell lines is at least partly achieved through inhibition of AURKB. No significant inhibition is observed for PLKs 1-3 (IC50s > 50 μM) probably due to the most divergent structure of PLK4 compared to other polo-like kinases 1-3. Cancer cells treated with CFI-400945 exhibit effects consistent with PLK4 kinase inhibition, including dysregulated centriole duplication, mitotic defects, and cell death. In vivo CFI-400945 is well tolerated in breast cancer xenograft models, in particular those deficient in the tumor suppressor PTEN. Upon intermittent oral dosing, in a mouse model of colon cancer, CFI-400945 is an effective inhibitor of HCT116 tumor growth and was well tolerated. CFI-400945 is absorbed rapidly after oral administration, reaching maximum plasma concentrations (Cmax) of 0.25-11.68 μg/mL for the doses tested (3.75-104 mg/kg). CFI-400945 can inhibit the growth of a range of tumor types and may be effective in a clinical setting even in advanced tumors. Following oral administration of efficacious doses of CFI-400945 in mice, plasma levels of CFI-400945 are sustained and remained above both the EC50 value for half-maximal inhibition of cellular PLK4 autophosphorylation and growth inhibition GI50 values for 24 hr. Moreover, CFI-400945 demonstrates dose-dependent antitumor activity. Analysis of xenograft tumors from mice treated with an efficacious dose of CFI-400945 shows a pharmacodynamic effect that is suggestive of complete rather than partial inhibition of PLK4 kinase activity. Cell Research(from reference) Cell lines:MDA-MB-468, MCF-7, HCC1954, MDA-MB-231, SKBr-3, Cal-51, and BT-20 breast cancer cells Concentrations:10 nM to 50 μM Incubation Time:5 d |
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IUPAC 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 |
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INCHI | 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 |
InChi Key | DADASRPKWOGKCU-FVTQAUBDSA-N |
Canonical SMILES | CC1CN(CC(O1)C)CC2=CC=C(C=C2)C=CC3=NNC4=C3C=CC(=C4)C5CC56C7=C(C=CC(=C7)OC)NC6=O |
Isomeric 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 |
PubChem CID | 58486178 |
Molecular Weight | 534.65 |
PubChem CID | 58486178 |
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CAS Registry No. | 1338806-73-7 |
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Lot Number | Certificate Type | Date | Item |
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K2212319 | Certificate of Analysis | Jun 20, 2022 | C413779 |
K2212324 | Certificate of Analysis | Jun 20, 2022 | C413779 |
K2212329 | Certificate of Analysis | Jun 20, 2022 | C413779 |
K2212331 | Certificate of Analysis | Jun 20, 2022 | C413779 |
K2212336 | Certificate of Analysis | Jun 20, 2022 | C413779 |
K2212358 | Certificate of Analysis | Jun 20, 2022 | C413779 |
Solubility | Solubility (25°C) In vitro DMSO: 100 mg/mL warmed with 50ºC Water: bath (187.03 mM); Ethanol: 100 mg/mL (187.03 mM); Water: Insoluble; |
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1. Sampson PB, Liu Y, Patel NK, Feher M, Forrest B, Li SW, Edwards L, Laufer R, Lang Y, Ban F et al.. (2015) The discovery of Polo-like kinase 4 inhibitors: design and optimization of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H).ones as orally bioavailable antitumor agents.. J Med Chem, 58 (1): (130-46). [PMID:24867403] |
2. Mason JM, Lin DC, Wei X, Che Y, Yao Y, Kiarash R, Cescon DW, Fletcher GC, Awrey DE, Bray MR et al.. (2014) Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent.. Cancer Cell, 26 (2): (163-76). [PMID:25043604] |