CFI-400945

製品コード：S7552 純度：99.56%

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

CAS No. 1338806-73-7

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40300	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 59500	国内在庫あり
100mg	JPY 149500	国内在庫なし(納期7~10日)
1g	JPY 595500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（7）

製品安全説明書

現在のバッチを見る：純度： 99.56%

99.56

CFI-400945関連製品

関連ターゲット	PLK1 PLK2 PLK3 PLK4	もっと見る
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関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

PLKシグナル伝達経路

PLK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
MCF7	Growth inhibition assay	5 days	Growth inhibition of human MCF7 cells after 5 days by SRB assay, GI50 = 0.008 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
A549	Growth inhibition assay	5 days	Growth inhibition of human A549 cells after 5 days by SRB assay, GI50 = 0.005 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
HCT116	Growth inhibition assay	5 days	Growth inhibition of human HCT116 cells after 5 days by SRB assay, GI50 = 0.004 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
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

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)	もっとクリックする
2.8 nM	6 nM	9 nM	22 nM	98 nM	もっとクリックする

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].
細胞実験	細胞株	MDA-MB-468, MCF-7, HCC1954, MDA-MB-231, SKBr-3, Cal-51, and BT-20 breast cancer cells
	濃度	10 nM to 50 μM
	反応時間	5 d
	実験の流れ	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.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	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].
動物実験	動物モデル	Adult female athymic CD1 nude mice
	投与量	10 mg/kg
	投与経路	via oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考
[1] Sampson PB, et al. J Med Chem. 2015, 58(1):147-69. [2] Yu B, et al. Eur J Med Chem. 2015, 95:35-40. [3] Mason JM, et al. Cancer Cell. 2014, 26(2):163-76.

参考

化学情報

分子量	534.65	化学式	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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 100 mg/mL ( (187.03 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 100 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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