Maraviroc

別名：UK-427857

製品コード：S2003 純度：99.99%

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM in cell-free assays, respectively. Maraviroc is used in the treatment of HIV infection.

CAS No. 376348-65-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 55500	国内在庫あり
100mg	JPY 115500	国内在庫あり
1g	JPY 295500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

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シグナル伝達経路

CCRシグナル伝達経路

CCR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
TZM-bl	Function assay	48 hrs	Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 YU2-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.00043 μM.	24563723
TZM-bl	Function assay	48 hrs	Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 MGC26-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.00037 μM.	24563723
TZM-bl	Function assay	3 days	Inhibition of CCR5 in human TZM-bl cells infected with HIV1 Bal R5 assessed as antiviral activity by measuring reduction in viral infection pre-incubated with cells followed by viral infection measured after 3 days by luciferase reporter gene assay, IC50 = 0.0002 μM.	28082070
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

CCR5 ^[3] (Cell-free assay)	MIP-1α ^[1] (Cell-free assay)	RANTES ^[1] (Cell-free assay)	MIP-1β ^[1] (Cell-free assay)
	3.3 nM	5.2 nM	7.2 nM

In Vitro
In vitro	Maraviroc inhibits MIP-1β-stimulated γ-S-GTP binding to HEK-293 cell membranes, indicating its ability to inhibit chemokine-dependent stimulation of GDP-GTP exchange at the CCR5/G protein complex. Maraviroc also inhibits the downstream event of chemokine-induced intracellular calcium redistribution, with IC50s ranging from 7 to 30 nM obtained against MIP-1β, MIP-1α and RANTES. In the same experiments, Maraviroc does not trigger release of intracellular calcium at concentrations up to 10 μM, indicating that it is devoid of CCR5 agonist activity. Consistent with this, Maraviroc fails to induce CCR5 internalization. Maraviroc is active at low nanomolar concentrations against HIV-1 Ba-L. Maraviroc inhibits all 200 pseudotyped viruses with a geometric mean IC90 of 13.7 nM. ^[1] At concentrations >1000 times the 50% inhibitory concentration, maraviroc did not inhibit other chemokine receptors (CCR1, 2, 3, 4, 7, and 8; CXCR1 and 2) to a clinically relevant degree^[3].
Kinase Assay	Inhibition of chemokine binding to CCR5
Kinase Assay	Binding of ¹²⁵I-labeled MIP-1α, MIP-1β, and RANTES to CCR5 is measured using intact HEK-293 cells stably expressing the receptor or membrane preparations thereof. Briefly, cells are resuspended in binding buffer (50 mM HEPES containing 1 mM CaCl₂, 5 mM MgCl₂, and 0.5% bovine serum albumin [BSA] and adjusted to pH 7.4) to a density of 2 × 10⁶ cells/ml. For membrane preparations, phosphate-buffered saline (PBS)-washed cells are resuspended in lysis buffer (20 mM HEPES, 1 mM CaCl₂, 1 tablet COMPLETE per 50 mL, pH 7.4) prior to homogenization in a Polytron hand-held homogenizer, ultracentrifugation (40,000× g for 30 min), and resuspension in binding buffer to a protein concentration of 0.25 mg/mL (12.5 μg of membrane protein is used in each well of a 96-well plate). ¹²⁵I-radiolabeled MIP-1α, MIP-1β, and RANTES are prepared and diluted in binding buffer to a final concentration of 400 pM in the assay. Maraviroc dilutions are added to each well to a final volume of 100 μL, the assay plates incubate for 1 hour, and the contents filter through preblocked and washed Unifilter plates which are counted following overnight drying.
細胞実験	細胞株	PHA-stimulated PBMC or PM-1 cells
	濃度	0-1 μM
	反応時間	5 days or 7 days
	実験の流れ	Drug susceptibility assays are performed in 24-well tissue culture plates. Duplicate eight-point dilution series of Maraviroc are prepared in DMSO and medium to yield a final DMSO concentration of 0.1% (vol/vol) in the assay. PHA-stimulated PBMC or PM-1 cells are infected with virus for 1 hour at 37 °C. Cells are subsequently washed once, and 3.6 × 10⁵ PBMC or 2.0 × 10⁵ PM-1 cells are added to each well of assay plates containing diluted Maraviroc. Plates are incubated for 5 days (lab-adapted strains) or 7 days (primary isolates) at 37 °C in a humidified 5% CO₂ (vol/vol) atmosphere.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	cleaved caspase-3 / cleaved caspase-9 / cleaved PARP / XIAP / Survivin / c-IAP1 / c-IAP2 / Bax / Bad / Bcl2 / Bcl-xl		28469959

In Vivo
In Vivo	The half-life values of Maraviroc are 0.9 hour in the rat and 2.3 hours in the dog. Following oral administration (2 mg/kg) to the dog, the Cmax (256 ng/ml) occurred 1.5 hours post-dose, and the bioavailability is 40%. For the rat, approximately 30% of the administered dose is absorbed from the intestinal tract. ^[1] Female RAG-hu mice are challenged vaginally with HIV-1 an hour after intravaginal application of the Maraviroc gel. Maraviroc gel treated mice are fully protected against vaginal HIV-1 challenge in contrast to placebo gel treated mice which all became infected. Vaginal administration of Maraviroc fully protects mice against HIV-1 vaginal challenge. While there is a clear pattern of CD4 T cell decline in placebo-gel treated and viral challenged mice, their levels are stable in mice receiving Maraviroc gel. ^[2]
動物実験	動物モデル	Humanized BALB/c-Rag2−/−γc−/− and BALB/c-Rag1−/−γc−/− (RAG-hu) mice
	投与量	~64 μg
	投与経路	A 25 μL volume of the gel formulation is carefully applied in to the vaginal vault of mice.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT04966429	Recruiting	Post Stroke Cognitive Impairment	Tel-Aviv Sourasky Medical Center\|Hadassah Medical Organization\|Soroka University Medical Center	May 1 2021	Phase 2
NCT04710199	Completed	Virus Diseases	Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	February 23 2021	Phase 2
NCT02881762	Completed	Hepatitis C\|Human Immunodeficiency Virus	University of Maryland Baltimore\|ViiV Healthcare	June 1 2017	Phase 4
NCT02778204	Completed	HIV Infections	National Institute of Allergy and Infectious Diseases (NIAID)\|Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)\|ViiV Healthcare\|GlaxoSmithKline	June 5 2017	Phase 1
NCT02741323	Completed	HIV Infections\|Kidney Diseases	National Institute of Allergy and Infectious Diseases (NIAID)	January 1 2017	Phase 2

参考
[1] Dorr P, et al. Antimicrob Agents Chemother. 2005, 49(11), 4721-4732. [2] Neff CP, et al. PLoS One. 2011, 6(6), e20209. [3] Lieberman-Blum SS, et al. Clin Ther. 2008, 30(7):1228-50.

参考

化学情報

分子量	513.67	化学式	C₂₉H₄₁F₂N₅O
CAS No.	376348-65-1	SDF	Download Maraviroc SDFをダウンロードする
Smiles	CC1=NN=C(N1C2CC3CCC(C2)N3CCC(C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C
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 ( (194.67 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
	Clear solution	5%DMSO 1 Corn oil	1.2mg/ml (2.34mM)	Taking the 1 mL working solution as an example, add 50 μL of 24 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.	投与溶液組成計算機
Clear solution	10% DMSO 1 40% PEG300 Click to order 2 5%Tween 80 Click to order 3 45% water	12.5mg/ml (24.33mM)	Taking the 1 mL working solution as an example, add 100 μL of 125mg/ml clear 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 clarify it; then continue adding Dilute 450 μL ddH2O to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 50%ddH2O	5.0mg/ml (9.73mM)	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.
Clear solution	5%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 50%ddH2O	7.5mg/ml (14.60mM)	Taking the 1 mL working solution as an example, add 50 μL of 150 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 clarify; 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.

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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よくある質問（FAQ）

質問1:
What’s the vehicle do you recommend to dissolve the compound for in vivo experiments?

回答
S2003 Maraviroc can be dissolved in 5% DMSO/castor oil at 62 mg/ml as suspension for oral administration. As to a clear solution for injection, following three vehicles at 10mg/ml will help: 1. 2% DMSO/castor oil; 2. 2%DMSO/sunflower oil; 3. 2%DMSO/30%PEG 300/ddH2O.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):