Name: CFI-400945
Brand: Selleck Chemicals
SKU: S7552
Availability: InStock
Rating: 5 (11 reviews)

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Quality Control

Batch: Purity: 99.56%

99.56

Related Targets	CDK HSP K-Ras PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras Aurora Kinase
Other PLK Products	Volasertib (BI6727) BI 2536 Rigosertib (ON-01910) GSK461364 Onvansertib (NMS-1286937, NMS-P937) SBE 13 HCl Ro3280 HMN-214 MLN0905 Poloxin

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (187.03 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.35mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	534.65	Formula	C₃₃H₃₄N₄O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1338806-73-7	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1CN(CC(O1)C)CC2=CC=C(C=C2)C=CC3=NNC4=C3C=CC(=C4)C5CC56C7=C(C=CC(=C7)OC)NC6=O

Mechanism of Action

Targets/IC₅₀/Ki	PLK4 (Cell-free assay) 2.8 nM TrkA (Cell-free assay) 6 nM TrkB (Cell-free assay) 9 nM Tie-2 (Cell-free assay) 22 nM Aurora B (Cell-free assay) 98 nM Aurora A (Cell-free assay) 140 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 this compound at a concentration of 50 μM. It can attenuate the growth of breast cell line, as well as other tumor cell lines significantly. This compound 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 this chemical 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 this agent 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, this compound is an effective inhibitor of HCT116 tumor growth and was well tolerated. It 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). This chemical 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 this compound in mice, plasma levels of it 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, it demonstrates dose-dependent antitumor activity. Analysis of xenograft tumors from mice treated with an efficacious dose of this chemical shows a pharmacodynamic effect that is suggestive of complete rather than partial inhibition of PLK4 kinase activity.
References	[1] https://pubmed.ncbi.nlm.nih.gov/25723005/ [2] https://pubmed.ncbi.nlm.nih.gov/25791677/ [3] https://pubmed.ncbi.nlm.nih.gov/25043604/

Applications

Methods	Biomarkers	Images	PMID
Growth inhibition assay	Cell viability		29434041

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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Handling Instructions

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CFI-400945 PLK inhibitor

Chemical Structure

Molecular Weight: 534.65