Bindarit | CAS#130641-38-2 | MCP-1 inhibitor

MedKoo Cat#: 319596 | Name: Bindarit

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Bindarit is a MCP-1 (Monocyte Chemotactic Protein-1) Synthesis inhibitor. Bindarit protects against bone loss induced by chikungunya virus infection. Bindarit inhibits human coronary artery smooth muscle cell proliferation, migration and phenotypic switching. Bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis. Bindarit prolongs survival and reduces renal damage in NZB/W lupus mice.

Chemical Structure

Bindarit

CAS# 130641-38-2

Theoretical Analysis

MedKoo Cat#: 319596

Name: Bindarit

CAS#: 130641-38-2

Chemical Formula: C19H20N2O3

Exact Mass: 324.1474

Molecular Weight: 324.38

Elemental Analysis: C, 70.35; H, 6.21; N, 8.64; O, 14.80

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,750.00	Ready to ship
2g	USD 6,250.00	Ready to ship

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Synonym

Bindarit; AF-2838; AF2838; AF 2838

IUPAC/Chemical Name

2-((1-benzyl-1H-indazol-3-yl)methoxy)-2-methylpropanoic acid

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)

SMILES Code

CC(C)(OCC1=NN(CC2=CC=CC=C2)C3=C1C=CC=C3)C(O)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A9T08K07

QC Data

View QC data: current batch, Lot#A9T08K07

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Bindarit (AF2838) is a selective inhibitor of the monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7, and MCP-2/CCL8.

In vitro activity:

Here, human myeloid MonoMac-6 (MM-6) cells were used to interrogate the molecular and cellular mechanisms underlying the immunomodulatory activity of bindarit on the expression of LPS-induced MCP-1 and IL-8. In unstimulated cells, bindarit alone did not change the basal expression of the two cytokines (data not shown). Stimulation of MM-6 with LPS caused a robust increase of both MCP-1 and IL-8 levels compared with unstimulated cells (Fig. 1). Unexpectedly, pretreatment with bindarit differentially impacted on the expression of the two chemokines, increasing of ∼1.5-fold the production of IL-8 (P < 0.001) while inhibiting of ∼3fold that of MCP-1 (P < 0.001; Fig. 1a,b). To ascertain the possible physical between bindarit and FABP4, competitive binding assays were performed, in which increasing concentrations of bindarit were used to displace radiolabeled fatty acids bound to FABP4. Bindarit was shown to be able to fully displace both [3H]-oleic acid and [3H]-arachidonic acid (Fig. 2a,b), with Ki values of 19 ± 3 μM and 60 ± 17 μM, respectively. In conclusion, this investigation demonstrates that the immunomodulatory effects of bindarit depend on its capacity to selectively bind FABP4, thus functionally altering its activity and localization. Sci Rep. 2019; 9: 15155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805920/

In vivo activity:

The effect of bindarit in vivo was investigated on phenotypic modulation of VSMCs in rat carotid arteries subjected to vascular injury. The oral administration of bindarit significantly (P<0.001) inhibited the neointimal growth at 14 and 28 days by 21% and 29% respectively (Supplementary data, Table S1). Similarly, bindarit reduced neointima/media ratio (see Supplementary results in Methods S11 and Table S1). Moreover bindarit significantly (P<0.001) induced an increase in lumen area at 14 and 28 days by 26% and 63%, respectively (Supplementary data, Table S1). These effects were associated with a significant reduction of MCP-1 levels in injured carotid arteries of rats treated with bindarit (Supplementary results in Methods S1 and Table S2). As shown in Figure 5A, treatment with bindarit significantly reduced the expression of SMemb at 14 and 28 days (by 31%, P<0.001 and 37%P<0.05, respectively) and increased the expression of calponin at 7 and 14 days (by 19%, P<0.05 and 47%, P<0.001). Bindarit also increased the expression of α-SMA at 14 and 28 days (by 13%, P<0.05 and 8%, P<0.01, respectively) and, as previously demonstrated, reduced the expression of PCNA at 7 days (by 44%, P<0.01) (Figure 5B). The data suggests novel underlying mechanisms by which bindarit can inhibit neointimal formation in human restenosis. PLoS One. 2012; 7(10): e47464. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471825/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.0	144.89

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 324.38 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Oddi S, Scipioni L, Totaro A, Angelucci C, Dufrusine B, Sabatucci A, Tortolani D, Coletta I, Alisi MA, Polenzani L, Assfalg M, Caltagirone C, Dainese E, Maccarrone M. The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells. Sci Rep. 2019 Oct 22;9(1):15155. doi: 10.1038/s41598-019-51691-y. PMID: 31641194; PMCID: PMC6805920. 2. Mora E, Guglielmotti A, Biondi G, Sassone-Corsi P. Bindarit: an anti-inflammatory small molecule that modulates the NFκB pathway. Cell Cycle. 2012 Jan 1;11(1):159-69. doi: 10.4161/cc.11.1.18559. Epub 2012 Jan 1. PMID: 22189654; PMCID: PMC3356824. 3. Liu S, Gao H, Gao C, Liu W, Xing D. Bindarit Attenuates Pain and Cancer-Related Inflammation by Influencing Myeloid Cells in a Model of Bone Cancer. Arch Immunol Ther Exp (Warsz). 2018 Jun;66(3):221-229. doi: 10.1007/s00005-017-0497-z. Epub 2017 Dec 12. PMID: 29234825. 4. Maddaluno M, Grassia G, Di Lauro MV, Parisi A, Maione F, Cicala C, De Filippis D, Iuvone T, Guglielmotti A, Maffia P, Mascolo N, Ialenti A. Bindarit inhibits human coronary artery smooth muscle cell proliferation, migration and phenotypic switching. PLoS One. 2012;7(10):e47464. doi: 10.1371/journal.pone.0047464. Epub 2012 Oct 15. PMID: 23077623; PMCID: PMC3471825.

In vitro protocol:

In vivo protocol:

1. Liu S, Gao H, Gao C, Liu W, Xing D. Bindarit Attenuates Pain and Cancer-Related Inflammation by Influencing Myeloid Cells in a Model of Bone Cancer. Arch Immunol Ther Exp (Warsz). 2018 Jun;66(3):221-229. doi: 10.1007/s00005-017-0497-z. Epub 2017 Dec 12. PMID: 29234825. 2. Maddaluno M, Grassia G, Di Lauro MV, Parisi A, Maione F, Cicala C, De Filippis D, Iuvone T, Guglielmotti A, Maffia P, Mascolo N, Ialenti A. Bindarit inhibits human coronary artery smooth muscle cell proliferation, migration and phenotypic switching. PLoS One. 2012;7(10):e47464. doi: 10.1371/journal.pone.0047464. Epub 2012 Oct 15. PMID: 23077623; PMCID: PMC3471825.

1: Colombo A, Basavarajaiah S, Limbruno U, Picchi A, Lettieri C, Valgimigli M, Sciahbasi A, Prati F, Calabresi M, Pierucci D, Guglielmotti A. A double-blind randomised study to evaluate the efficacy and safety of bindarit in preventing coronary stent restenosis. EuroIntervention. 2015 Dec 23;11(8). pii: 20140918-01. doi: 10.4244/EIJY15M12_03. [Epub ahead of print] PubMed PMID: 26690313. 2: Chen W, Foo SS, Taylor A, Lulla A, Merits A, Hueston L, Forwood MR, Walsh NC, Sims NA, Herrero LJ, Mahalingam S. Correction for Chen et al., Bindarit, an Inhibitor of Monocyte Chemotactic Protein Synthesis, Protects against Bone Loss Induced by Chikungunya Virus Infection. J Virol. 2015 Dec 1;89(23):12232. doi: 10.1128/JVI.02114-15. PubMed PMID: 26543092; PubMed Central PMCID: PMC4645307. 3: Zoja C, Corna D, Locatelli M, Rottoli D, Pezzotta A, Morigi M, Zanchi C, Buelli S, Guglielmotti A, Perico N, Remuzzi A, Remuzzi G. Effects of MCP-1 inhibition by bindarit therapy in a rat model of polycystic kidney disease. Nephron. 2015;129(1):52-61. doi: 10.1159/000369149. Epub 2014 Dec 17. PubMed PMID: 25531096. 4: Chen W, Foo SS, Taylor A, Lulla A, Merits A, Hueston L, Forwood MR, Walsh NC, Sims NA, Herrero LJ, Mahalingam S. Bindarit, an inhibitor of monocyte chemotactic protein synthesis, protects against bone loss induced by chikungunya virus infection. J Virol. 2015 Jan;89(1):581-93. doi: 10.1128/JVI.02034-14. Epub 2014 Oct 22. Erratum in: J Virol. 2015 Dec 1;89(23):12232. PubMed PMID: 25339772; PubMed Central PMCID: PMC4301140. 5: Steiner JL, Davis JM, McClellan JL, Guglielmotti A, Murphy EA. Effects of the MCP-1 synthesis inhibitor bindarit on tumorigenesis and inflammatory markers in the C3(1)/SV40Tag mouse model of breast cancer. Cytokine. 2014 Mar;66(1):60-8. doi: 10.1016/j.cyto.2013.12.011. Epub 2014 Jan 20. PubMed PMID: 24548426; PubMed Central PMCID: PMC4419732. 6: Severini C, Passeri PP, Ciotti M, Florenzano F, Possenti R, Zona C, Di Matteo A, Guglielmotti A, Calissano P, Pachter J, Mercanti D. Bindarit, inhibitor of CCL2 synthesis, protects neurons against amyloid-β-induced toxicity. J Alzheimers Dis. 2014;38(2):281-93. doi: 10.3233/JAD-131070. PubMed PMID: 23948942. 7: Maddaluno M, Grassia G, Di Lauro MV, Parisi A, Maione F, Cicala C, De Filippis D, Iuvone T, Guglielmotti A, Maffia P, Mascolo N, Ialenti A. Bindarit inhibits human coronary artery smooth muscle cell proliferation, migration and phenotypic switching. PLoS One. 2012;7(10):e47464. doi: 10.1371/journal.pone.0047464. Epub 2012 Oct 15. PubMed PMID: 23077623; PubMed Central PMCID: PMC3471825. 8: Paccosi S, Musilli C, Mangano G, Guglielmotti A, Parenti A. The monocyte chemotactic protein synthesis inhibitor bindarit prevents mesangial cell proliferation and extracellular matrix remodeling. Pharmacol Res. 2012 Dec;66(6):526-35. doi: 10.1016/j.phrs.2012.09.006. Epub 2012 Sep 14. PubMed PMID: 22982961. 9: Ge S, Shrestha B, Paul D, Keating C, Cone R, Guglielmotti A, Pachter JS. The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis. J Neuroinflammation. 2012 Jul 12;9:171. doi: 10.1186/1742-2094-9-171. PubMed PMID: 22788993; PubMed Central PMCID: PMC3488971. 10: Zollo M, Di Dato V, Spano D, De Martino D, Liguori L, Marino N, Vastolo V, Navas L, Garrone B, Mangano G, Biondi G, Guglielmotti A. Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models. Clin Exp Metastasis. 2012 Aug;29(6):585-601. doi: 10.1007/s10585-012-9473-5. Epub 2012 Apr 7. PubMed PMID: 22484917. 11: Mora E, Guglielmotti A, Biondi G, Sassone-Corsi P. Bindarit: an anti-inflammatory small molecule that modulates the NFκB pathway. Cell Cycle. 2012 Jan 1;11(1):159-69. doi: 10.4161/cc.11.1.18559. Epub 2012 Jan 1. PubMed PMID: 22189654; PubMed Central PMCID: PMC3356824. 12: Rulli NE, Rolph MS, Srikiatkhachorn A, Anantapreecha S, Guglielmotti A, Mahalingam S. Protection from arthritis and myositis in a mouse model of acute chikungunya virus disease by bindarit, an inhibitor of monocyte chemotactic protein-1 synthesis. J Infect Dis. 2011 Oct 1;204(7):1026-30. doi: 10.1093/infdis/jir470. PubMed PMID: 21881117. 13: Ialenti A, Grassia G, Gordon P, Maddaluno M, Di Lauro MV, Baker AH, Guglielmotti A, Colombo A, Biondi G, Kennedy S, Maffia P. Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries. Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2448-54. doi: 10.1161/ATVBAHA.111.230078. PubMed PMID: 21852559. 14: Rulli NE, Guglielmotti A, Mangano G, Rolph MS, Apicella C, Zaid A, Suhrbier A, Mahalingam S. Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with bindarit, an inhibitor of monocyte chemotactic proteins. Arthritis Rheum. 2009 Aug;60(8):2513-23. doi: 10.1002/art.24682. PubMed PMID: 19644852. 15: Grassia G, Maddaluno M, Guglielmotti A, Mangano G, Biondi G, Maffia P, Ialenti A. The anti-inflammatory agent bindarit inhibits neointima formation in both rats and hyperlipidaemic mice. Cardiovasc Res. 2009 Dec 1;84(3):485-93. doi: 10.1093/cvr/cvp238. Epub 2009 Jul 10. PubMed PMID: 19592568; PubMed Central PMCID: PMC2777949. 16: Bhatia M, Landolfi C, Basta F, Bovi G, Ramnath RD, de Joannon AC, Guglielmotti A. Treatment with bindarit, an inhibitor of MCP-1 synthesis, protects mice against trinitrobenzene sulfonic acid-induced colitis. Inflamm Res. 2008 Oct;57(10):464-71. doi: 10.1007/s00011-008-7210-y. PubMed PMID: 18827968. 17: Mirolo M, Fabbri M, Sironi M, Vecchi A, Guglielmotti A, Mangano G, Biondi G, Locati M, Mantovani A. Impact of the anti-inflammatory agent bindarit on the chemokinome: selective inhibition of the monocyte chemotactic proteins. Eur Cytokine Netw. 2008 Sep;19(3):119-22. doi: 10.1684/ecn.2008.0133. Epub 2008 Sep 8. PubMed PMID: 18775807. 18: Bhatia M, Ramnath RD, Chevali L, Guglielmotti A. Treatment with bindarit, a blocker of MCP-1 synthesis, protects mice against acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2005 Jun;288(6):G1259-65. Epub 2005 Feb 3. PubMed PMID: 15691869. 19: Guglielmotti A, D'Onofrio E, Coletta I, Aquilini L, Milanese C, Pinza M. Amelioration of rat adjuvant arthritis by therapeutic treatment with bindarit, an inhibitor of MCP-1 and TNF-alpha production. Inflamm Res. 2002 May;51(5):252-8. PubMed PMID: 12056513. 20: Guglielmotti A, Aquilini L, D'Onofrio E, Rosignoli MT, Milanese C, Pinza M. Bindarit prolongs survival and reduces renal damage in NZB/W lupus mice. Clin Exp Rheumatol. 1998 Mar-Apr;16(2):149-54. PubMed PMID: 9536390.