CFI-400945

Catalog No.S7552

For research use only.

CFI-400945 is an orally active, potent and selective polo-like kinase 4(PLK4) inhibitor with Ki value of 0.26 nM.

CFI-400945 Chemical Structure

CAS No. 1338806-73-7

Selleck's CFI-400945 has been cited by 4 Publications

Purity & Quality Control

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Biological Activity

Description CFI-400945 is an orally active, potent and selective polo-like kinase 4(PLK4) inhibitor with Ki value of 0.26 nM.
Targets
PLK4 [1]
(Cell-free assay)
TrkA [1]
(Cell-free assay)
TrkB [1]
(Cell-free assay)
Tie-2 [1]
(Cell-free assay)
Aurora B [1]
(Cell-free assay)
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2.8 nM 6 nM 9 nM 22 nM 98 nM
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[2]. Cancer cells treated with CFI-400945 exhibit effects consistent with PLK4 kinase inhibition, including dysregulated centriole duplication, mitotic defects, and cell death[3].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 MXjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MlrNOUBl[Xm| M1\RUWdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGhEXDFzNjDj[YxteyCjZoTldkA2KGSjeYOgZpkhW1KEIHHzd4F6NCCJSUWwJF0hOC5yMESg{txONg>? MmTZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5MkOwNFUoRjJ3N{KzNFA2RC:jPh?=
HCC1954 NHvPdGVIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M2fOelUh\GG7cx?= MWnHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDIR2MyQTV2IHPlcIx{KGGodHXyJFUh\GG7czDifUBUWkJiYYPzZZktKEeLNUCgQUAxNjByNTFOwG0v NGrURpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyN|AxPSd-MkW3NlMxODV:L3G+
A549 NFH3cYJIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NG\OWHE2KGSjeYO= NXviN2xsT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hSTV2OTDj[YxteyCjZoTldkA2KGSjeYOgZpkhW1KEIHHzd4F6NCCJSUWwJF0hOC5yMEWg{txONg>? NGC3WHc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyN|AxPSd-MkW3NlMxODV:L3G+
MDA-MB-468 NU\vfVVVT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M4LTbFUh\GG7cx?= NUHyc3IxT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVUSDLV3CMVQ3QCClZXzsd{Bi\nSncjC1JIRigXNiYomgV3JDKGG|c3H5MEBIUTVyIE2gNE4xODZizszNMi=> NFnxVYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyN|AxPSd-MkW3NlMxODV:L3G+
MCF7 NWGxUph5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NVjQc3R[PSCmYYnz MmjWS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gUWNHPyClZXzsd{Bi\nSncjC1JIRigXNiYomgV3JDKGG|c3H5MEBIUTVyIE2gNE4xODhizszNMi=> NHvYRWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyN|AxPSd-MkW3NlMxODV:L3G+
COLO205 M1PCZmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NVHQOJJqPSCmYYnz M4HjdWdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGNQVE9{MEWgZ4VtdHNiYX\0[ZIhPSCmYYnzJIJ6KFOUQjDhd5NigSxiR1m1NEA:KDBwMEG3JO69VS5? MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{M{CwOUc,OjV5MkOwNFU9N2F-
OVCAR3 M3viWWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MVK1JIRigXN? MojWS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gU3ZESVJ|IHPlcIx{KGGodHXyJFUh\GG7czDifUBUWkJiYYPzZZktKEeLNUCgQUAxNjBzODFOwG0v M2\G[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{KzNFA2Lz5{NUeyN|AxPTxxYU6=
BT20 NEmwc|JIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MoTGOUBl[Xm| M2G2cWdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGJVOjBiY3XscJMh[W[2ZYKgOUBl[Xm|IHL5JHNTSiCjc4PhfUwhT0l3MDC9JFAvODV6IN88UU4> MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{M{CwOUc,OjV5MkOwNFU9N2F-
CAL51 NVTWbpB5T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NV\ScolKPSCmYYnz MYjHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDDRWw2OSClZXzsd{Bi\nSncjC1JIRigXNiYomgV3JDKGG|c3H5MEBIUTVyIE2gNE4zPiEQvF2u Mn\NQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5MkOwNFUoRjJ3N{KzNFA2RC:jPh?=
SW620 NEXmfWRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NI\ESng2KGSjeYO= MnXHS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gV3c3OjBiY3XscJMh[W[2ZYKgOUBl[Xm|IHL5JHNTSiCjc4PhfUwhT0l3MDC9JFAvOzhizszNMi=> NU[4dnhvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3NlMxODVpPkK1O|I{ODB3PD;hQi=>
SKBR3 M2fuZ2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MXG1JIRigXN? NIDJPFdIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBUU0KUMzDj[YxteyCjZoTldkA2KGSjeYOgZpkhW1KEIHHzd4F6NCCJSUWwJF0hPS5|IN88UU4> M3LRNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{KzNFA2Lz5{NUeyN|AxPTxxYU6=
MDA-MB-231 M3\Xbmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NHTGNHE2KGSjeYO= MVfHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDNSGEuVUJvMkOxJINmdGy|IHHmeIVzKDViZHH5d{BjgSCVUlKgZZN{[XluIFfJOVAhRSB6Lk[g{txONg>? NXK3RnBiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3NlMxODVpPkK1O|I{ODB3PD;hQi=>
HMEC MVHHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? MYi1JIRigXN? NYnxS|JKT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUE2HQzDj[YxteyCjZoTldkA2KGSjeYOgZpkhW1KEIHHzd4F6NCCJSUWwJF0hQSEQvF2u Mn\5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5MkOwNFUoRjJ3N{KzNFA2RC:jPh?=
Assay
Methods Test Index PMID
Growth inhibition assay Cell viability 29434041
In vivo CFI-400945 is well tolerated in breast cancer xenograft models, in particular those deficient in the tumor suppressor PTEN[2]. 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[1]. 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[3].

Protocol (from reference)

Cell Research:

[1]

  • 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
  • Method:
    MDA-MB-468, MCF-7, HCC1954, MDA-MB-231, SKBr-3, Cal-51, and BT-20 breast cancer cells are seeded into 96-well plates at 3000, 4000, 4000, 2500, 4000, 3000, and 6000 cells per 80 μL, respectively, 24 h before compound overlay and cultured at 37℃ and 5% CO2. Compounds are prepared as 10 mM stocks in 100% DMSO. Each 10 mM stock is diluted with DMEM (Dulbecco's Modified Eagle's Medium) cell growth medium containing 10% FBS such that the final concentrations ranged from 50 nM to 250 μM. Aliquots (20 μL) from each concentration are overlaid to 80 μL of preseeded cells to achieve final concentrations of 10 nM to 50 μM. After 5 d, the cells are fixed in situ by gently removing the culture media and adding 50 μL of ice-cold 10% trichloroacetic acid (TCA) per well and incubation at 4 °C for 30 min. The plates are washed with water five times and allowed to air-dry for 5 min. Then 50 μL of 0.4% (w/v) sulforhodamine B (SRB) solution in 1% (v/v) acetic acid is added to each well,
    followed by incubation for 30 min at rt. The plates are washed four times with 1% acetic acid to remove unbound SRB and air-dried for 5 min. The SRB is solubilized with 100 μL of 10 mM Tris pH 10.5 per well, and absorbance is read at 570 nm. The percentage (%) of relative inhibition of cell viability is calculated.
Animal Research:

[1]

  • Animal Models: Adult female athymic CD1 nude mice
  • Dosages: 10 mg/kg
  • Administration: via oral gavage

Solubility (25°C)

In vitro

DMSO 100 mg/mL warmed
(187.03 mM)
Ethanol 100 mg/mL
(187.03 mM)
Water Insoluble

Chemical Information

Molecular Weight 534.65
Formula

C33H34N4O3

CAS No. 1338806-73-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1CN(CC(O1)C)CC2=CC=C(C=C2)C=CC3=NNC4=C3C=CC(=C4)C5CC56C7=C(C=CC(=C7)OC)NC6=O

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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04730258 Recruiting Drug: CFI-400945|Drug: Azacitidine|Drug: Decitabine Acute Myeloid Leukemia|Myelodysplastic Syndromes|Chronic Myelomonocytic Leukemia|AML|MDS|CMML Treadwell Therapeutics Inc April 16 2021 Phase 1|Phase 2
NCT04176848 Recruiting Drug: CFI-400945|Drug: Durvalumab Breast Cancer Canadian Cancer Trials Group|AstraZeneca|University Health Network Toronto December 19 2019 Phase 2
NCT03624543 Recruiting Drug: CFI-400945 Breast Cancer Canadian Cancer Trials Group|Stand Up To Cancer Canada-Canadian Cancer Society Breast Cancer Dream Team December 21 2018 Phase 2
NCT03187288 Active not recruiting Drug: CFI-400945 Fumarate Acute Myeloid Leukemia|Myelodysplastic Syndromes|Relapsed Cancer|Refractory Cancer University Health Network Toronto May 25 2018 Phase 1
NCT01954316 Active not recruiting Drug: CFI-400945 Advanced Cancer University Health Network Toronto|Princess Margaret Cancer Foundation|California Institute for Regenerative Medicine (CIRM) March 2014 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

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