product name Bindarit
Description: Bindarit (also known as AF 2838) exhibits selective inhibition against monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7 and MCP-2/CCL8. Bindarit treatment causes a dose-dependent inhibition of the capacity of human monocytes to produce monocyte chemotactic protein-1 (MCP-1) in response to bacterial LPS or C. albicans with IC50 of 172 µM and 403 µM, respectively. The inhibition of LP-induced MCP-1 production by Bindarit is associated with reduced levels of MCP-1 mRNA transcripts with IC50 of 75 µM. Bindarit inhibits the production of MCP-1 by LPS-stimulated MM6 cells with IC50 of 425 μM, without affecting the release of IL-8 or IL-6.
References: Kidney Int. 1998 Mar;53(3):726-34; Eur Cytokine Netw. 1999 Sep;10(3):437-42; J Invest Dermatol. 2007 Aug;127(8):2031-41.
324.37
Formula
C19H20N2O3
CAS No.
130641-38-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 65 mg/mL (200.4 mM)
Water: <1 mg/mL
Ethanol: 65 mg/mL (200.4 mM)
Solubility (In vivo)
0.5% CMC: 7 mg/mL
Synonyms
AF 2838
other peoduct :
| In Vitro |
In vitro activity: Bindarit treatment causes a dose-dependent inhibition of the capacity of human monocytes to produce monocyte chemotactic protein-1 (MCP-1) in response to bacterial LPS or C. albicans with IC50 of 172 µM and 403 µM, respectively. The inhibition of LP-induced MCP-1 production by Bindarit is associated with reduced levels of MCP-1 mRNA transcripts with IC50 of 75 µM. Bindarit inhibits the production of MCP-1 by LPS-stimulated MM6 cells with IC50 of 425 μM, without affecting the release of IL-8 or IL-6. Bindarit treatment inhibits the release of MCP-1 from IL-1 stimulated osteoblast cell line Saos-2. Bindarit, even at the maximal concentration, does not exhibit a direct in vitro cytotoxic effect on human IIB-MEL-J melanoma or ECs, although it inhibits MCP-1 expression. Bindarit (10-300 μM) reduces rat vascular smooth muscle cell (VSMC) proliferation, migration, and invasion. Bindarit induces the downregulation of the classical NF-κB pathway. Bindarit displays a specific inhibitory effect on the p65 and p65/p50 induced MCP-1 promoter activation, with no effect on other tested activated promoters, indicating that Bindarit acts on a specific subpopulation of NF-κB isoforms and selects its targets within the whole NF-κB inflammatory pathway. Bindarit modulates cancer-cell proliferation and migration, mainly through negative regulation of TGF-β and AKT signaling. Kinase Assay: Cell Assay: Bindarit inhibited MCP-1 and TNF-alpha production induced in monocytes by LPS and Candida albicans in a dose-dependent manner with the IC50 of 172 µM and 403 µM, respectively.The inhibition of LP-induced MCP-1 production by Bindarit has been associated with the reduced levels of MCP-1 mRNA transcripts with the IC50 value of 75 µM. Bindaritexihibited an inhibitory effect in the production of MCP-1 by LPS-stimulated MM6 cells with an IC50 of 425 μM, without affecting the release of IL-8 or IL-6[3].Administration of bindarit (10-300 μM) reduced rat vascular smooth muscle cell (VSMC) proliferation, migration, and invasion. |
|---|---|
| In Vivo | Oral administration of Bindarit at 50 mg/kg in NZB/W mice delays the onset of proteinuria, significantly protects from renal function impairment, and prolongs survival of NZB/W mice or lupus mice. Bindarit treatment completely MCP-1 up-regulation during the progression of nephritis. Inhibition of MCP-1 with Bindarit also reduces tumor growth and macrophage recruitment, rendering necrotic tumor masses in human melanoma xenografts. Bindarit is effective in reducing neointima formation in both non-hyperlipidaemic and hyperlipidaemic animal models of vascular injury by a direct effect on VSMC proliferation and migration and by reducing neointimal macrophage content. Administration of Bindarit results in impaired metastatic disease in prostate cancer PC-3M-Luc2 xenograft mice and impairment of local tumorigenesis in Balb/c mice with murine breast cancer 4T1-Luc cells. In addition, Bindarit treatment significantly decreases the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in 4T1-Luc primary tumors. |
| Animal model | NZB/W F1 female mice with a spontaneous autoimmune disease |
| Formulation & Dosage | Formulated in 0.5% carboxy-methylcellulose; ~50 mg/kg/day; Oral gavage |
| References | Kidney Int. 1998 Mar;53(3):726-34; Eur Cytokine Netw. 1999 Sep;10(3):437-42; J Invest Dermatol. 2007 Aug;127(8):2031-41. |
