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CFI-400945

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

CFI-400945 Chemical Structure

CAS: 1338806-73-7

Selleck's CFI-400945 has been cited by 7 publications

Purity & Quality Control

Batch: Purity: 99.56%
99.56

CFI-400945 Related Products

Signaling Pathway

PLK Signaling Pathways

PLK Signaling Pathway

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 Growth inhibition assay 5 days Growth inhibition of human HCT116 cells after 5 days by SRB assay, GI50 = 0.004 μM. 25723005
HCC1954 Growth inhibition assay 5 days Growth inhibition of human HCC1954 cells after 5 days by SRB assay, GI50 = 0.005 μM. 25723005
A549 Growth inhibition assay 5 days Growth inhibition of human A549 cells after 5 days by SRB assay, GI50 = 0.005 μM. 25723005
MDA-MB-468 Growth inhibition assay 5 days Growth inhibition of human MDA-MB-468 cells after 5 days by SRB assay, GI50 = 0.006 μM. 25723005
MCF7 Growth inhibition assay 5 days Growth inhibition of human MCF7 cells after 5 days by SRB assay, GI50 = 0.008 μM. 25723005
COLO205 Growth inhibition assay 5 days Growth inhibition of human COLO205 cells after 5 days by SRB assay, GI50 = 0.017 μM. 25723005
OVCAR3 Growth inhibition assay 5 days Growth inhibition of human OVCAR3 cells after 5 days by SRB assay, GI50 = 0.018 μM. 25723005
BT20 Growth inhibition assay 5 days Growth inhibition of human BT20 cells after 5 days by SRB assay, GI50 = 0.058 μM. 25723005
CAL51 Growth inhibition assay 5 days Growth inhibition of human CAL51 cells after 5 days by SRB assay, GI50 = 0.26 μM. 25723005
SW620 Growth inhibition assay 5 days Growth inhibition of human SW620 cells after 5 days by SRB assay, GI50 = 0.38 μM. 25723005
SKBR3 Growth inhibition assay 5 days Growth inhibition of human SKBR3 cells after 5 days by SRB assay, GI50 = 5.3 μM. 25723005
MDA-MB-231 Growth inhibition assay 5 days Growth inhibition of human MDA-MB-231 cells after 5 days by SRB assay, GI50 = 8.6 μM. 25723005
HMEC Growth inhibition assay 5 days Growth inhibition of human HMEC cells after 5 days by SRB assay, GI50 = 9 μM. 25723005
Click to View More Cell Line Experimental Data

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)		 Click to View More Targets
2.8 nM 6 nM 9 nM 22 nM 98 nM
In vitro
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 Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Growth inhibition assay Cell viability 29434041
In Vivo
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].
Animal Research Animal Models Adult female athymic CD1 nude mice
Dosages 10 mg/kg
Administration via oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04730258 Recruiting
Acute Myeloid Leukemia|Myelodysplastic Syndromes|Chronic Myelomonocytic Leukemia|AML|MDS|CMML
Treadwell Therapeutics Inc
 April 16 2021 Phase 1|Phase 2
NCT04176848 Unknown status
Breast Cancer
Canadian Cancer Trials Group|AstraZeneca|University Health Network Toronto
 December 19 2019 Phase 2
NCT03624543 Active not recruiting
Breast Cancer
Canadian Cancer Trials Group|Stand Up To Cancer Canada-Canadian Cancer Society Breast Cancer Dream Team
 February 14 2019 Phase 2
NCT03187288 Active not recruiting
Acute Myeloid Leukemia|Myelodysplastic Syndromes|Relapsed Cancer|Refractory Cancer
University Health Network Toronto
 May 25 2018 Phase 1
NCT01954316 Completed
Advanced Cancer
University Health Network Toronto|The Princess Margaret Cancer Foundation|California Institute for Regenerative Medicine (CIRM)
 March 2014 Phase 1

Chemical Information & Solubility

Molecular Weight 534.65 Formula

C33H34N4O3
CAS No. 1338806-73-7 SDF --
Smiles CC1CN(CC(O1)C)CC2=CC=C(C=C2)C=CC3=NNC4=C3C=CC(=C4)C5CC56C7=C(C=CC(=C7)OC)NC6=O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (187.03 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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