| Identification | Back Directory | [Name]
Bindarit | [CAS]
130641-38-2 | [Synonyms]
AF 2838
CS-1989
Bindarit
AF2838;AF-2838;AF 2838
2-[(1-benzylindazol-3-yl)methoxy]-2-methylpropanoic acid
2-[(1-Benzyl-1H-indazol-3-yl)methoxy]-2-methylpropionic acid
2-((1-Benzyl-1H-indazol-3-yl)Methoxy)-2-Methylpropanoic acid
Propanoic acid, 2-Methyl-2-[[1-(phenylMethyl)-1H-indazol-3-yl]Methoxy]- | [Molecular Formula]
C19H20N2O3 | [MDL Number]
MFCD00866723 | [MOL File]
130641-38-2.mol | [Molecular Weight]
324.37 |
| Chemical Properties | Back Directory | [Boiling point ]
542.9±40.0 °C(Predicted) | [density ]
1.18±0.1 g/cm3 (20 ºC 760 Torr) | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
DMSO:47.0(Max Conc. mg/mL);144.89(Max Conc. mM) | [form ]
A crystalline solid | [pka]
3.59±0.10(Predicted) | [color ]
White to off-white | [InChI]
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) | [InChIKey]
MTHORRSSURHQPZ-UHFFFAOYSA-N | [SMILES]
C(O)(=O)C(C)(OCC1C2=C(N(CC3=CC=CC=C3)N=1)C=CC=C2)C |
| Hazard Information | Back Directory | [Description]
Bindarit is an inhibitor of monocyte chemoattractant protein (MCP) production that is selective for MCP-1/CCL2, MPC-3/CCL7, and MCP-2/CCL8 over other chemokines.1 It inhibits LPS- or C. albicans-induced production of MCP-1/CCL2 in isolated human monocytes (IC50s = 172 and 403 μM, respectively).2 Bindarit downregulates NF-κB signaling and prevents p65 and p65/p50-mediated MCP-1/CCL2 promoter activation in RAW264.7 cells.3 It delays the onset of proteinuria and prolongs survival in a mouse model of experimental lupus nephritis when administered at a dose of 50 mg/kg.4 It prevents LPS-induced increases in MCP-1/CCL2 expression in mouse brain and spinal cord when administered at a dose of 200 mg/kg and reduces the incidence and severity of experimental autoimmune encephalomyelitis (EAE) in mice.5 Bindarit is also a noncompetitive inhibitor of monocarboxylate transporter 4 (MCT4; Ki = 30.2 μM for the human transporter) that is selective for MCT4 over MCT1.6 | [Uses]
Bindarit exhibits selective inhibition against monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7 and MCP-2/CCL8. | [Uses]
Bindarit shows anti-inflammatory activity due to a selective inhibition of a subfamily of inflammatory chemokines. Bindarit is a also protein antidenaturant agent. Bindarit modulates the NFkB pathway and has been shown to reduce secondary phase of adjuvant arthritis in rats. | [in vivo]
Bindarit (50 mg/kg; oral administration; every day; for 4 months, 6 months, 8 months; NZB/W F1 female mice) delays the onset of proteinuria and significantly protects from renal function impairment. Bindarit completely prevents monocyte chemoattractant protein (MCP-1) up-regulation[2]. | Animal Model: | NZB/W F1 female mice ( two months of age)[2] | | Dosage: | 50 mg/kg | | Administration: | Oral administration; every day; for 4 months, 6 months, 8 months | | Result: | Delayed the onset of proteinuria and significantly protected from renal function impairment.
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| [References]
[1] MASSIMILIANO MIROLO. Impact of the anti-inflammatory agent bindarit on the chemokinome: selective inhibition of the monocyte chemotactic proteins.[J]. European cytokine network, 2008, 19 3: 119-122. DOI: 10.1684/ecn.2008.0133
[2] M SIRONI. A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1.[J]. European cytokine network, 1999, 10 3: 437-442.
[3] EUGENIO MORA. Bindarit: an anti-inflammatory small molecule that modulates the NFκB pathway.[J]. Cell Cycle, 2012, 11 1: 159-169. DOI: 10.4161/cc.11.1.18559
[4] CARLA ZOJA. Bindarit retards renal disease and prolongs survival in murine lupus autoimmune disease[J]. Kidney international, 1998, 53 3: Pages 726-734. DOI: 10.1046/j.1523-1755.1998.00804.x
[5] SHUJUN GE. The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis.[J]. Journal of Neuroinflammation, 2012: 171. DOI: 10.1186/1742-2094-9-171
[6] YUYA FUTAGI . Identification of a selective inhibitor of human monocarboxylate transporter 4[J]. Biochemical and biophysical research communications, 2018, 495 1: Pages 427-432. DOI: 10.1016/j.bbrc.2017.10.025 |
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