Riviciclib hydrochloride (P276-00)

製品コード：S8058 純度：99.26%

Riviciclib hydrochloride (P276-00) is a novel CDK1, CDK4 and CDK9 inhibitor with IC50 of 79 nM, 63 nM and 20 nM, respectively. Riviciclib hydrochloride (P276-00) induces apoptosis. Phase 2/3.

CAS No. 920113-03-7

サイズ	価格(税別)	在庫状況
5mg	JPY 40500	国内在庫あり

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（6）

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製品安全説明書

現在のバッチを見る： S805801 DMSO] 88 mg/mL] false] Water] 88 mg/mL] false] Ethanol] 7 mg/mL] false 純度： 99.26%

99.26

Riviciclib hydrochloride (P276-00)関連製品

関連ターゲット	CDK1 CDK2 CDK3 CDK4 CDK5 CDK6 CDK7 CDK9 CLK Cdc CDK8 CDK12 CDK13 CDK19 CDK11 CDK/cyclin complexes	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

CDKシグナル伝達経路

CDK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	活性情報	PMID
KB-3-1	qHTS assay	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen.	31515284
KB-8-5-11	qHTS assay	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen, Potency = 5.1735 μM.	31515284
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

Targets

CDK9/CyclinT1 ^[1]	CDK4/CyclinD1 ^[1]	CDK1/CyclinB ^[1]	CDK2/CyclinA ^[1]	CDK6/CyclinD3 ^[1]	もっとクリックする
20 nM	63 nM	79 nM	224 nM	396 nM	もっとクリックする

In Vitro
In vitro	P276-00 shows 40-fold selectivity toward Cdk4-D1, compared with Cdk2-E^[1]. It shows potent antiproliferative effects against various human cancer cell lines, including HCT-116, U2OS, H-460, HL-60, HT-29, SiHa, MCF-7, Colo-205, SW-480, PC-3, Caco2, T-24 with an IC50 ranging from 300 to 800 nmol/L, and is found to be highly selective for cancer cells as compared with normal fibroblast cells^[1]. P276-00 can down-regulate cyclin D1 and Cdk4 in an ATP- competitive manner and decrease Cdk4-specific pRb Ser780 phosphorylation. P276-00 also induces apoptosis by actving cellular caspase-3 activity and DNA ladder formation^[1].
Kinase Assay	Cdk4-D1/Cdk2-E enzyme assay
Kinase Assay	The Cdk4-D1/Cdk2-E enzyme assay is run in 96-well format using Millipore Multiscreen filtration plates. All assay steps are done in a single filter plate. The filtration wells are prewetted with 100 μL of kinase buffer [50 mmol/L HEPES (pH, 7.5), 10 mmol/L MgCl₂, 1 mmol/L EGTA], and then the solution is removed by vacuum. With filter plate on vacuum manifold, 50 μL GST-Rb bound to GSH-Sepharose beads in kinase buffer (0.5 μg GST-Rb/50 μL) is added to each well, and vacuum is applied to the filter plate. About 25 μL of a reaction mix containing ATP (cold + hot) and 4× phosphatase inhibitor mix (40 μmol/L unlabeled ATP, 10 μCi/mL γ³²P-ATP, 40 mmol/L h-glycerophosphate, 4 mmol/L DTT, 0.4 mmol/L NaF, 0.4 mmol/L sodium orthovanadate) diluted in kinase buffer is added to each well. The test compound (4×final concentration in kinase buffer) or kinase buffer alone (control) is then added in an additional 25 μL volume. To each well, 50 μL (100 ng) of human Cdk4-D1/Cdk2-E enzyme in kinase buffer is added to initiate the reaction, which is allowed to continue for 30 min at 30°C. When the reaction is completed, vacuum is applied again, and the plate is washed with the TNEN buffer [20 mmol/L Tris (pH, 8.0), 100 mmol/L NaCl, 1 mmol/L EDTA, 0.5% nonidet-P40] thrice; the filter plate is air-dried and is placed in a Multiscreen adapter plate. Packard Microscint-O cocktail (30 μL) is added, and the plate is covered with a Top-Seal A film. Quantitation of ³²P-GST-Rb in 96-well filter plates is carried out by Top Count scintillation counter. All compounds are tested initially at 1 μmol/L concentration. Compounds showing more than or equal to 50% inhibition are further profiled for IC50 determination.
細胞実験	細胞株	HCT-116, U2OS, H-460, HL-60, HT-29, SiHa, MCF-7, Colo-205, SW-480, PC-3, Caco2, T-24
	濃度	~5.0 μM
	反応時間	48 h
	実験の流れ	The cells are seeded at a density of 3,000-5,000 cells per well, depending on cell type in 180 μL of culture medium in 96-well plate and incubated overnight to allow the cells to adhere. Varying concentrations of compounds are added to the wells and incubated for 48 h at 37°C. ³H-thymidine (0.25 μCi) is added to each well, and incorporation of the radiolabel is allowed to proceed for 5 to 7 h. Following this incubation, cells are harvested onto GF/B unifilter plates using a Packard Filtermate Universal harvester, and the plates are counted in a Packard Top Count 96-well liquid scintillation counter.

In Vivo
In Vivo	P276-00, administered i.p. at 50 mg/kg daily for 20 treatments can significantly induce growth inhibition of murine colon cancer (CA-51). However, in murine lung carcinoma model (Lewis lung), an increased dose of 60 mg/kg (30 mg/kg twice daily) administered every alternate day i.p. for 7 treatments shows significant inhibition in the growth^[2]. And it also inhibit the growth of human colon carcinoma HCT-116 xenograft and human non-small cell lung carcinoma H-460 xenograft^[2]. Efficacy Studies show its maximum tolerated dose is 78 mg/kg/d^[2].
動物実験	動物モデル	H-460 xenograft
	投与量	50 mg/kg once daily or 30 mg/kg twice daily
	投与経路	i.p.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00899054	Completed	Squamous Cell Carcinoma of Head and Neck	Piramal Enterprises Limited	August 2009	Phase 1\|Phase 2
NCT00898287	Completed	Pancreatic Cancer	Piramal Enterprises Limited	May 2009	Phase 1\|Phase 2
NCT00547404	Withdrawn	Multiple Myeloma	Piramal Enterprises Limited	December 2008	Phase 1
NCT00882063	Completed	Relapsed and/or Refractory Multiple Myeloma	Piramal Enterprises Limited	January 2008	Phase 1\|Phase 2
NCT00407498	Completed	Neoplasm	Piramal Enterprises Limited	May 2005	Phase 1

参考
[1] Joshi KS, et al. Mol Cancer Ther, 2007, 6(3), 918-925. [2] Joshi KS, et al. Mol Cancer Ther, 2007, 6(3), 926-934.

参考

化学情報

分子量	438.3	化学式	C₂₁H₂₀ClNO₅.HCl
CAS No.	920113-03-7	SDF	Download Riviciclib hydrochloride (P276-00) SDFをダウンロードする
Smiles	CN1CCC(C1CO)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O.Cl
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 : 88 mg/mL ( (200.77 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。)

Water : 88 mg/mL

Ethanol : 7 mg/mL

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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