Bindarit (AF2838)

Alias: AF-2838; AF2838; Bindarit; AF 2838

Cat No.:V2026 Purity: ≥98%

COA Product Data Instructions for use SDS

Bindarit (also known as AF-2838; AF 2838) is a potent and selective inhibitor of monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7 and MCP-2/CCL8 with anti-inflammatory activity.

Bindarit (AF2838) Chemical Structure CAS No.: 130641-38-2
Product category: CCR

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

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

Cell 2020,183:1202-1218.e25.

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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.

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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

Bindarit (also known as AF-2838; AF 2838) is a potent and selective inhibitor of monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7 and MCP-2/CCL8 with anti-inflammatory activity. Bindarit treatment inhibits human monocytes' ability to produce monocyte chemotactic protein-1 (MCP-1) in response to 403 µM and 172 µM, respectively, when exposed to bacterial LPS or Candida albicans. This effect is dose-dependent. With an IC50 of 75 µM, lower levels of MCP-1 mRNA transcripts are linked to Bindarit's inhibition of LP-induced MCP-1 production. When LPS-stimulated MM6 cells are exposed to bindarit, their production of MCP-1 is inhibited (IC50 = 425 μM), but neither IL-8 nor IL-6 are released.

Biological Activity I Assay Protocols (From Reference)

Targets

MCP-1/CCL2; MCP-3/CCL7; MCP-2/CCL8

ln Vitro

In vitro activity: Bindarit treatment inhibits human monocytes' ability to produce monocyte chemotactic protein-1 (MCP-1) in response to 403 µM and 172 µM, respectively, when exposed to bacterial LPS or Candida albicans. This effect is dose-dependent. With an IC50 of 75 µM, lower levels of MCP-1 mRNA transcripts are linked to Bindarit's inhibition of LP-induced MCP-1 production. When LPS-stimulated MM6 cells are exposed to bindarit, their production of MCP-1 is inhibited (IC50 = 425 μM), but neither IL-8 nor IL-6 are released.[2]
Bindarit treatment prevents the IL-1-stimulated osteoblast cell line Saos-2 from releasing MCP-1.[3]
Bindarit, does not directly cause cytotoxicity in vitro in human IIB-MEL-J melanoma or ECs, even at the highest concentration; however, it does suppress MCP-1 expression.[4] Bindarit (10-300 μM) inhibits the proliferation, migration, and invasion of rat vascular smooth muscle cells (VSMCs).[5]
Bindarit causes the traditional NF-κB pathway to be downregulated. With no effect on other tested activated promoters, Bindarit specifically inhibits the activation of the p65 and p65/p50 induced MCP-1 promoter. This suggests that Bindarit selectively targets a subpopulation of NF-κB isoforms within the entire NF-κB inflammatory pathway.[6]
Bindarit primarily regulates TGF-β and AKT signaling negatively in order to modify the migration and proliferation of cancer cells.[7]

ln Vivo

In mice with lupus or NZB/W backgrounds, oral administration of Bindarit at a dose of 50 mg/kg significantly protects against impairment of renal function and delays the onset of proteinuria. MCP-1 up-regulation during the course of nephritis is fully inhibited by bindarit treatment.[1] In human melanoma xenografts, inhibition of MCP-1 with Bindarit yields necrotic tumor masses by reducing tumor growth and macrophage recruitment.[4] Bindarit has a direct impact on VSMC proliferation and migration, as well as neointimal macrophage content, which effectively reduces the formation of neointima in both hyperlipidemic and non-hyperlipidemic animal models of vascular injury.[5] When Balb/c mice with murine breast cancer 4T1-Luc cells are administered Bindarit, the mice's ability to develop local tumors is reduced and their prostate cancer PC-3M-Luc2 xenograft mice showed less metastatic disease. Furthermore, the administration of Bindarit considerably reduces the infiltration of myeloid-derived suppressor cells and tumor-associated macrophages in 4T1-Luc primary tumors.[7]

Cell Assay

In a dose-dependent manner, bindarit inhibited the production of MCP-1 and TNF-alpha in monocytes induced by LPS and Candida albicans, with IC50 values of 172 µM and 403 µM, respectively.With an IC50 value of 75 µM, lower levels of MCP-1 mRNA transcripts have been linked to Bindarit's inhibition of LP-induced MCP-1 production. Without influencing the release of IL-8 or IL-6, bindaritex demonstrated an IC50 of 425 μM inhibitory effect on the production of MCP-1 by LPS-stimulated MM6 cells[3]. Rat vascular smooth muscle cell (VSMC) invasion, migration, and proliferation were all decreased by bindarit (10–300 μM) administration.

Animal Protocol

Formulated in 0.5% carboxy-methylcellulose; ~50 mg/kg/day; Oral gavage

NZB/W F1 female mice with a spontaneous autoimmune disease

References

[1]. Kidney Int . 1998 Mar;53(3):726-34.

[2]. Eur Cytokine Netw . 1999 Sep;10(3):437-42.

[3]. Inflamm Res . 2002 May;51(5):252-8.

[4]. J Invest Dermatol . 2007 Aug;127(8):2031-41.

[5]. Cardiovasc Res . 2009 Dec 1;84(3):485-93.

[6]. Cell Cycle . 2012 Jan 1;11(1):159-69.

[7]. Clin Exp Metastasis . 2012 Aug;29(6):585-601.

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

Physicochemical Properties

Molecular Formula

C19H20N2O3

Molecular Weight

324.37

Exact Mass

324.15

Elemental Analysis

C, 70.35; H, 6.21; N, 8.64; O, 14.80

CAS #

130641-38-2

Related CAS #

130641-38-2

Appearance

Solid powder

SMILES

CC(C)(C(=O)O)OCC1=NN(C2=CC=CC=C21)CC3=CC=CC=C3

InChi Key

MTHORRSSURHQPZ-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H20N2O3/c1-19(2,18(22)23)24-13-16-15-10-6-7-11-17(15)21(20-16)12-14-8-4-3-5-9-14/h3-11H,12-13H2,1-2H3,(H,22,23)

Chemical Name

2-[(1-benzylindazol-3-yl)methoxy]-2-methylpropanoic acid

Synonyms

AF-2838; AF2838; Bindarit; AF 2838

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

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: ~65 mg/mL (~200.4 mM)

Water: <1 mg/mL

Ethanol: ~65 mg/mL (~200.4 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.67 mg/mL (8.23 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 26.7 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.

Solubility in Formulation 2: ≥ 2.67 mg/mL (8.23 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 26.7 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.

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Solubility in Formulation 3: 2.67 mg/mL (8.23 mM) in 10% DMSO + 90% Corn Oil (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 26.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 4: 0.5% CMC: 7 mg/mL

Solubility in Formulation 5: 5 mg/mL (15.41 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O 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	3.0829 mL	15.4145 mL	30.8290 mL
	5 mM	0.6166 mL	3.0829 mL	6.1658 mL
	10 mM	0.3083 mL	1.5414 mL	3.0829 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
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

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.

Concentration (Start)

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Concentration (End)

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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)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

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.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
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)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

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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.)

% DMSO

% Tween 80

% ddH₂O

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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
NCT01109212	Completed	Drug: Bindarit Drug: Placebo	Diabetic Nephropathy	Aziende Chimiche Riunite Angelini Francesco S.p.A	March 2007	Phase 2
NCT01269242	Completed	Drug: Bindarit Drug: Placebo	Coronary Restenosis	Aziende Chimiche Riunite Angelini Francesco S.p.A	January 2009	Phase 2

Biological Data

Bindarit transcriptional effects on LPS-induced inflammatory chemokine. Cell Cycle . 2012 Jan 1;11(1):159-69.
(A) Effect of bindarit (10–300 µM) on rat VSMC proliferation, (B) migration, and (C) invasion performed as described in Section 2. Cardiovasc Res . 2009 Dec 1;84(3):485-93.