Maraviroc

製品コードS2003 バッチS200308

印刷

化学情報

Synonyms

UK-427857

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₉H₄₁F₂N₅O

分子量

513.67

CAS No.

376348-65-1

Solubility (25°C)*

体外

DMSO

100 mg/mL (194.67 mM)

Ethanol

100 mg/mL (194.67 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

10% DMSO 1 40% PEG 300 2 5%Tween80 3 45% water

12.5mg/ml

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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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].
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]

プロトコル(参考用のみ)

キナーゼアッセイ	Inhibition of chemokine binding to CCR5
キナーゼアッセイ	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.
細胞アッセイ	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.
動物実験	動物モデル	Humanized BALB/c-Rag2−/−γc−/− and BALB/c-Rag1−/−γc−/− (RAG-hu) mice
	投薬量	~64 μg
	投与方法	A 25 μL volume of the gel formulation is carefully applied in to the vaginal vault of mice.

参考

カスタマーフィードバック

: Data from [Cancer Res, 2012, 72(15), 3839-50]

: , 2010, Dr. Johanna Weiss of University Hospital Heidelberg

: Data from [Data independently produced by , , Clin Cancer Res, 2018, 78(7):1657-1671]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration [ Neuron, 2023, S0896-6273(23)00268-4]	PubMed: 37105172
CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice [ J Transl Med, 2023, 21(1):196]	PubMed: 36918921
Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes [ Neural Regen Res, 2023, 18(1):141-149]	PubMed: 35799534
Acute antagonism in three-drug combinations for vaginal HIV prevention in humanized mice [ Sci Rep, 2023, 13(1):4594]	PubMed: 36944714
Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods [ Cell Rep Methods, 2023, 3(6):100485]	PubMed: 37426753
Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer [ Theranostics, 2022, 12(17):7351-7370]	PubMed: 36438499
Tumor bud-derived CCL5 recruits fibroblasts and promotes colorectal cancer progression via CCR5-SLC25A24 signaling [ J Exp Clin Cancer Res, 2022, 41(1):81]	PubMed: 35241150
The analgesic properties of Yu-Xue-Bi tablets in the inflammatory pain mice: By the inhibition of CCL3-mediated macrophage transmigration into the spinal cord [ J Ethnopharmacol, 2022, 289:115051]	PubMed: 35101573
Imatinib Mesylate Exerted Antitumor Effect by Promoting Infiltration of Effector T Cells in Tumor [ Biol Pharm Bull, 2022, 45(1):34-41]	PubMed: 34980779
Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling [ Cell Res, 2021, 10.1038/s41422-021-00528-3]	PubMed: 34239070

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。