Cenicriviroc Mesylate

Alias: TBR-652 mesylate; TBR 652 mesylate; TAK-652 mesylate; TAK652 mesylate; TAK 652; TBR652; Cenicrivirocmesylate

Cat No.:V3747 Purity: ≥98%

COA Product Data Instructions for use SDS

Cenicriviroc Mesylate Chemical Structure CAS No.: 497223-28-6
Product category: CCR

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Cenicriviroc Mesylate:

Cenicriviroc

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Cenicriviroc Mesylate (formerly known as TAK-652 Mesylate or TBR-652 Mesylate) is a novel, orally bioactive, and dual antagonist of CCR2/CCR5, it also inhibits both HIV-1 and HIV-2, and has the potential for the treatment of HIV infection. TAK-652 inhibited the binding of MIP-1beta, macrophage inflammatory protein 1alpha (MIP-1alpha), and RANTES (regulated on activation, normal T-cell expressed and secreted) to CCR5-expressing cells at nanomolar concentrations. Additionally, TAK-652 may prevent monocyte chemotactic protein 1 (MCP-1) from attaching itself to cells that express CCR2b. Its ability to prevent ligand binding to other chemokine receptors was, nevertheless, somewhat restricted. TAK-652 exhibited activity against HIV-1 that used CCR5 (R5), but it was completely inert against HIV-1 that used CXCR4 (X4).

Biological Activity I Assay Protocols (From Reference)

Targets

CCR5 ( IC50 = 0.29 nM ); CCR2 ( IC50 = 5.9 nM ); R5 HIV-1 ( IC50 = 0.024-0.08 nM ); R5 HIV-2 ( IC50 = 0.03-0.98 nM )

ln Vitro

In vitro activity: After being pre-treated with 1 μM of cenicriviroc mesylate (CVC), mouse monocyte migration in response to carbon tetrachloride (CCL2) is decreased. The average fold change in migrating cells (±SD) for CCL2-stimulated cells treated with Cenicriviroc Mesylate is 0.8±0.2 (p>0.05) and 0.7±0.4 (p>0.05) for unstimulated cells treated with Cenicriviroc Mesylate, respectively, in comparison to untreated and unstimulated cells[1]. The four R5-tropic HIV-2 isolates have a median EC50 for Cenicriviroc Mesylate of 0.39 nM (0.03, 0.33, 0.45, and 0.98 nM) according to phenotypic susceptibility testing. The HIV-2 strains classified as dual-tropic and X4-tropic exhibit resistance to cenicriviroc mesylate, with an EC50 of more than 1000 nM and maximum percentages of inhibition (MPI) of 33% and 4%, in that order[2].

ln Vivo

Cenicriviroc Mesylate (CVC) treatment results in a dose-dependent reduction in the recruitment of monocytes and macrophages, reaching statistical significance at doses greater than 20 mg/kg/day (p<0.05). The peritoneal lavage monocyte/macrophage counts for Cenicriviroc Mesylate 5 twice daily (BID), Cenicriviroc Mesylate 20 twice daily (BID), Cenicriviroc Mesylate 100 BID, and Cenicriviroc Mesylate 20 once-daily (QD) show decreases of 5.7%, 45.2%, 76.5%, and 26.0%, respectively, in comparison to the vehicle-control group. Cenicriviroc Mesylate exposure is dose-dependent and associated with a reduction in monocyte/macrophage recruitment. It seems to work better when administered as part of a BID dose rather than a QD dose, which is consistent with the higher plasma concentrations obtained with BID dosing and the medication's known short half-life in mice (2 hours)[1].

Enzyme Assay

Cenicriviroc blocks HIV-1 from entering cells at an effective concentration of 50% EC50 of 0.03, 0.33, 0.45, and 0.98 nM for the four R5 HIV-2 clinical isolates that were tested. Cenicriviroc resistance in the dual-tropic and X4-tropic HIV-2 strains is >1000 nM for EC50 and 33% and 4% for MPI, respectively.

Cell Assay

Three separate assessments are made ex vivo of mouse monocyte migration in response to Cenicriviroc Mesylate (CVC) treatment. In male C57BL/6 mice (n = 3; 8–10 weeks old), thioglycollate (TG) is injected intraperitoneally. 48 hours later, activated macrophages are extracted through peritoneal lavage. A 1 μM solution of cenicriviroc mesylate is added to the cells and incubated for two hours. Flow cytometry is used to count the number of F4/80⁺CD11b⁺ macrophages by analyzing cells extracted from the lower compartment. With FlowJo software, results are analyzed[1].

Animal Protocol

Male C57BL/6 mice (n = 44; 8–10 weeks old) are divided into 5 groups and given oral gavage (PO) treatments on Days 1–5. These groups include non-disease control, vehicle control twice daily (BID), Cenicriviroc Mesylate 5 mg/kg/day (CVC5) BID, Cenicriviroc Mesylate 20 mg/kg/day (CVC20) BID, Cenicriviroc Mesylate 100 mg/kg/day (CVC100) BID, and Cenicriviroc Mesylate 20 mg/kg once-daily (10 QD). With the exception of the non-disease controls, all groups undergo IP injections of thioglycollate (TG) 3.85% (1 mL/animal) two hours post-dose to induce peritonitis on Day 4[1].

References

[1]. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. PLoS One. 2016 Jun 27;11(6):e0158156.

[2]. Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates. PLoS One. 2015 Aug 6;10(8):e0134904.

[3]. Safety, efficacy, and pharmacokinetics of TBR-652, a CCR5/CCR2 antagonist, in HIV-1-infected, treatment-experienced, CCR5 antagonist-naive subjects. J Acquir Immune Defic Syndr. 2011 Jun 1;57(2):118-25.

[4]. TAK-652 inhibits CCR5-mediated human immunodeficiency virus type 1 infection in vitro and has favorable pharmacokinetics in humans. Antimicrob Agents Chemother. 2005 Nov;49(11):4584-91.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C42H56N4O7S2

Molecular Weight

793.05

Exact Mass

792.36

Elemental Analysis

C, 63.61; H, 7.12; N, 7.06; O, 14.12; S, 8.09

CAS #

497223-28-6

Related CAS #

Cenicriviroc; 497223-25-3

Appearance

Solid powder

SMILES

CCCCOCCOC1=CC=C(C=C1)C2=CC/3=C(C=C2)N(CCC/C(=C3)/C(=O)NC4=CC=C(C=C4)[S@@](=O)CC5=CN=CN5CCC)CC(C)C.CS(=O)(=O)O

InChi Key

IXPBPUPDRDCRSY-YLZLUMLXSA-N

InChi Code

InChI=1S/C41H52N4O4S.CH4O3S/c1-5-7-22-48-23-24-49-38-15-10-32(11-16-38)33-12-19-40-35(25-33)26-34(9-8-21-44(40)28-31(3)4)41(46)43-36-13-17-39(18-14-36)50(47)29-37-27-42-30-45(37)20-6-2;1-5(2,3)4/h10-19,25-27,30-31H,5-9,20-24,28-29H2,1-4H3,(H,43,46);1H3,(H,2,3,4)/b34-26+;/t50-;/m0./s1

Chemical Name

(5E)-8-[4-(2-butoxyethoxy)phenyl]-1-(2-methylpropyl)-N-[4-[(S)-(3-propylimidazol-4-yl)methylsulfinyl]phenyl]-3,4-dihydro-2H-1-benzazocine-5-carboxamide;methanesulfonic acid

Synonyms

TBR-652 mesylate; TBR 652 mesylate; TAK-652 mesylate; TAK652 mesylate; TAK 652; TBR652; Cenicrivirocmesylate

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~126.1 mM）

Water: N/A

Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (3.15 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.08 mg/mL (2.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (2.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.2610 mL	6.3048 mL	12.6095 mL
	5 mM	0.2522 mL	1.2610 mL	2.5219 mL
	10 mM	0.1261 mL	0.6305 mL	1.2610 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

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

Molecular mass (or 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.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05630885	Active Recruiting	Drug: CVC 150 mg Drug: CVC 300 mg	HIV-1-infection	National Institute of Allergy and Infectious Diseases (NIAID)	May 30, 2023	Phase 2
NCT02684799	Completed	Drug: Cenicriviroc Drug: Omeprazole Drug: Famotidine	Healthy	Tobira Therapeutics, Inc.	January 31, 2016	Phase 1
NCT02342067	Completed	Drug: Cenicriviroc Drug: Pioglitazone	Healthy	Tobira Therapeutics, Inc.	December 2014	Phase 1
NCT02685462	Completed	Drug: Rosuvastatin Drug: Atorvastatin Drug: Simvastatin Drug: Digoxin Drug: Caffeine	Healthy	Tobira Therapeutics, Inc.	January 31, 2016	Phase 1
NCT04500418	Terminated	Drug: Cenicriviroc (CVC) Drug: Placebo	Covid19	Charite University, Berlin, Germany	August 25, 2020	Phase 2

Biological Data

Inhibitory effect of TAK-652 on binding of RANTES (A), MIP-1α (B), and MIP-1β (C) to CCR5.Antimicrob Agents Chemother.2005 Nov;49(11):4584-91.

Inhibitory effect of TAK-652 on ligand binding to various chemokine receptors.CHO cells expressing CCR1 (open circles), CCR2b (open squares), CCR3 (filled triangles), CCR4 (open triangles), or CCR7 (filled circles) were incubated with various concentrations of TAK-652 in binding buffer containing125I-labeled RANTES, MCP-1, eotaxin, TARC, or MIP-3β, respectively. Binding reactions were performed at room temperature and terminated by washing out the cell-free ligand with PBS. The cell-associated radioactivity was measured with a scintillation counter. Data represent means ± standard deviations for triplicate wells.Antimicrob Agents Chemother.2005 Nov;49(11):4584-91.

Antiviral activity of TAK-652 against R5X4 HIV-1 in U87.CD4.CCR5 and U87.CD4.CXCR4 cells. The cells were infected with R5X4 HIV-1 (HE) and incubated in the presence of test compounds (100 nM). After incubation for 6 h, the cells were washed to remove unadsorbed viral particles and further incubated in the presence of the same concentration of the test compounds for 3 days.

Cenicriviroc Mesylate Plasma concentration-time profiles after single oral administration of TAK-652 to humans.Antimicrob Agents Chemother.2005 Nov;49(11):4584-91.