Maraviroc (UK-427857)

For research use only.

Catalog No.S2003

32 publications

Maraviroc (UK-427857) Chemical Structure

CAS No. 376348-65-1

Maraviroc (UK-427857) 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.

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Selleck's Maraviroc (UK-427857) has been cited by 32 publications

Purity & Quality Control

Choose Selective CCR Inhibitors

Biological Activity

Description Maraviroc (UK-427857) 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.
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

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].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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PM1 MXHBcpRqfmm{YXygZZN{[Xl? Mn\oOUBl[Xm| MUDBcpRqfmm{YXygZYN1cX[rdImgZYdicW6|dDDDR3I2NWSncHXu[IVvfCCKSW[xJGJiNUxiaX7m[YN1\WRiaX6gbJVu[W5iUF2xJINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiC4aYL1d{Bqdm[nY4Tpc44hdWWjc4Xy[YQh[W[2ZYKgOUBl[Xm|IHL5JIx2[2moZYLhd4UhemWyb4L0[ZIh\2WwZTDhd5NigSxiSVO1NEA:KDBwMECxJO69VS5? NXvtNVdtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CyN|Q{ODBpPkOwNlM1OzByPD;hQi=>
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HOS NV74ZYV4SW62aY\pdoFtKGG|c3H5 NFznTHg2KGSjeYO= MnzERY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgR2NTPS2mZYDlcoRmdnRiSFnWNUBD[S2OIHnu[oVkfGWmIHnuJIh2dWGwIFjPV{Bk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5idnnyeZMhcW6oZXP0bY9vKG2nYYP1doVlKGGodHXyJFUh\GG7czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFnDOVAhRSByLkCwNVkh|ryPLh?= M2L2dFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkO0N|AxLz5|MEKzOFMxODxxYU6=
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JC53-BL NV\WWoVISW62aY\pdoFtKGG|c3H5 Mn7JN{Bl[Xm| MWDBcpRqfmm{YXygZYN1cX[rdImgZYdicW6|dDDDR3I2NXS{b4DpZ{Bz\WOxbXLpcoFvfCCKSW[xJG5NSmGuII\pdpV{KGmwZnXjeIVlKGmwIFrDOVMuSkxiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kB3cXKjbDDy[ZBtcWOjdHnvckBi\nSncjCzJIRigXNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCLQ{WwJF0hOC5yMEK4JO69VS5? MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODF|N{mzO{c,OjBzM{e5N|c9N2F-
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CHO MlP1SpVv[3Srb36gZZN{[Xl? NGP2UIUyOCCvaX7z MnqwRY51[WexbnnzeEBi[3Srdnn0fUBi\2GrboP0JGNEWjViKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gR2hQKGOnbHzzJINwNWW6cILld5NqdmdiR3HsdIhiOTZiaX7jeYJifGWmIH\vdkAyOCCvaX7zJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gVmFPXEWVLXnu[JVk\WRiY3HsZ4l2dSCvb3LpcIl7[XSrb36sJGlEPTBiPTCwMlAyOzFizszNMi=> NH\PVYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[zPFQ6QCd-MkW2N|g1QTh:L3G+
CHO M1\FbmZ2dmO2aX;uJIF{e2G7 NGHNPVMyOCCvaX7z MVTJcohq[mm2aX;uJI9nKEOFUkWgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO|ZXSgbY4hS0iRIHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhWkGQVFXTMYlv\HWlZXSgbY51emGlZXzseYxieiCFYUKrJI1w[mmuaYrheIlwdiCjZoTldkAyOCCvaX7zJIJ6KE[udX:tOEBCVSC|dHHpcolv\y2kYYPl[EBndHWxcnXzZ4Vv[2ViYYPzZZktKEmFNUCgQUAxNjB{NUSzJO69VS5? NVjUe5NWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzNVY3PjlpPkK0N|E3PjZ7PD;hQi=>
HEK293 NV3TRYZ4TnWwY4Tpc44h[XO|YYm= M{fDflEvPSCvaX7z Ml3CTY5pcWKrdHnvckBw\iCqdX3hckBOSVSHMT3t[YRq[XSnZDDBV3AsKHWydHHr[UBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzJIFnfGW{IEGuOUBucW6|IHL5JIZtfW:{ZYPj[Y5k\SCjc4PhfUwhUUN3MDC9JFE4NjNizszNMi=> MnX5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{NEGwNlkoRjJ|MkSxNFI6RC:jPh?=
A673 M2XNSJFJXFNiYYPzZZk> Mmi5dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN? M13YSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB1643 M1fjdpFJXFNiYYPzZZk> NWnYbG1{eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=> MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
NB-EBc1 MWfxTHRUKGG|c3H5 MXfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDORk1GSmNzIHPlcIx{ MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh30 MoPrdWhVWyCjc4PhfS=> M2f6WJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpOzBiY3XscJM> NVTQNGQ1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
RD NXLTTnFIeUiWUzDhd5NigQ>? MnLQdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVmQh[2WubIO= NYLGbllQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC NVHISZFKeUiWUzDhd5NigQ>? MnTvdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tUWMh[2WubIO= NVX3UZhFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643 MnHadWhVWyCjc4PhfS=> NHPJfZNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBPSjF4NEOgZ4VtdHN? M1zWU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC M{ixTJFJXFNiYYPzZZk> NGi5TYZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLV3DJINmdGy| MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SJ-GBM2 MVXxTHRUKGG|c3H5 Mn;SdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2ouT0KPMjDj[Yxtew>? M2[4ZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh18 M4rJTZFJXFNiYYPzZZk> Mn7pdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgVogyQCClZXzsdy=> NWr5TWJQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
cleaved caspase-3 / cleaved caspase-9 / cleaved PARP / XIAP / Survivin / c-IAP1 / c-IAP2 / Bax / Bad / Bcl2 / Bcl-xl; 

PubMed: 28469959     


The cells were treated with specified dose of maraviroc and western blotting was performed. Dose-dependent increased in protein expression of cleaved caspase 3/9 and PARP cleavage was observed in SUP-B15 cells after maraviroc treatment. GAPDH was used as loading control. 

28469959
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]

Protocol

Kinase Assay:

[1]

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Inhibition of chemokine binding to CCR5:

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.
Cell Research:

[1]

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  • Cell lines: PHA-stimulated PBMC or PM-1 cells
  • Concentrations: 0-1 μM
  • Incubation Time: 5 days or 7 days
  • Method:

    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.


    (Only for Reference)
Animal Research:

[2]

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  • Animal Models: Humanized BALB/c-Rag2−/−γc−/− and BALB/c-Rag1−/−γc−/− (RAG-hu) mice
  • Dosages: ~64 μg
  • Administration: A 25 μL volume of the gel formulation is carefully applied in to the vaginal vault of mice.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (194.67 mM)
Water Insoluble
Ethanol '''100 mg/mL
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+corn oil
For best results, use promptly after mixing.
10mg/mL

* 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.

Chemical Information

Molecular Weight 513.67
Formula

C29H41F2N5O

CAS No. 376348-65-1
Storage powder
in solvent
Synonyms N/A
Smiles CC1=NN=C(N1C2CC3CCC(C2)N3CCC(C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C

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 ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04710199 Recruiting Drug: Maraviroc experimental group|Other: Standard treatment Virus Diseases Fundación Pública Andaluza para la gestión de la Investigación en Sevilla February 8 2021 Phase 2
NCT02881762 Completed Drug: Maraviroc Hepatitis C|Human Immunodeficiency Virus University of Maryland Baltimore|ViiV Healthcare June 1 2017 Phase 4
NCT02778204 Completed Drug: Maraviroc 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
NCT02626923 Completed -- Drug-induced Hypotension Nicholaos C Bellos MD|GlaxoSmithKline|Southwest Infectious Disease Clinical Research Inc. July 2012 --

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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Frequently Asked Questions

  • Question 1:

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

  • Answer:

    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.

CCR Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID