Vesnarinone

• CAT Number: I004968
• CAS Number: 81840-15-5
• Molecular Formula: C22H25N3O4
• Molecular Weight: 395.45
• Purity: ≥95%
• Target: PDE3
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 1.1 μM (for HERG current)
• InChI: InChI=1S/C22H25N3O4/c1-28-19-7-3-16(14-20(19)29-2)22(27)25-11-9-24(10-12-25)17-5-6-18-15(13-17)4-8-21(26)23-18/h3,5-7,13-14H,4,8-12H2,1-2H3,(H,23,26)
• InChIKey: ZVNYJIZDIRKMBF-UHFFFAOYSA-N
• SMILES: O=C1NC2=C(C=C(N3CCN(C(C4=CC=C(OC)C(OC)=C4)=O)CC3)C=C2)CC1

Vesnarinone is a quinolinone derivative, and its pharmacodynamic effects include inhibition of phosphodiesterase III (PDE3) activity, increases in calcium flux and decreases in potassium flux.IC50 value: 1.1 μM (for HERG current)Target: PDE3in vitro: HERG current is inhibited by Vesnarinone with an IC50 of 1.1 μM, whereas KvLQT1/minK current is not significantly depressed by Vesnarinone even at 30 μM. The IC50 value for Vesnarinone inhibition of HERG channels is 1 μM. The IC50 for Vesnarinone inhibition of PDE is reported to be 300 μM. [1] Vesnarinone is a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase. [2] Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. Vesnarinone inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. Vesnarinone has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits.[3] Vesnarinone plays an important role in the regulation of cytokines and suggest that the reduction of cytokine release may contribute to the beneficial effects of the drug in the treatment of heart failure. Vesnarinone inhibits the production of TFN-a and IFN-y by LPS stimulated whole blood from patients with heart failure and from healthy volunteers. [4]in vivo: Vesnarinone reduces the circulating levels of TNF-α. Cumulative evidence showed that a variety of cytokine are involved in the pathogenesis of pulmonary fibrosis. [2]

Reference

1:Vesnarinone suppresses TNFα mRNA expression by inhibiting valosin-containing protein. Hotta K, Nashimoto A, Yasumura E, Suzuki M, Azuma M, Iizumi Y, Shima D, Nabeshima R, Hiramoto M, Okada A, Sakata-Sogawa K, Tokunaga M, Ito T, Ando H, Sakamoto S, Kabe Y, Aizawa S, Imai T, Yamaguchi Y, Watanabe H, Handa H.Mol Pharmacol. 2013 May;83(5):930-8. doi: 10.1124/mol.112.081935. Epub 2013 Feb 7. PMID: 23393163 Free Article2:Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells. Uchida D, Onoue T, Begum NM, Kuribayashi N, Tomizuka Y, Tamatani T, Nagai H, Miyamoto Y.Mol Cancer. 2009 Aug 12;8:62. doi: 10.1186/1476-4598-8-62. PMID: 19671192 Free PMC Article3:Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin. Inage M, Nakamura H, Saito H, Abe S, Hino T, Takabatake N, Terashita K, Ogura M, Kato S, Hosokawa T, Sata M, Tomoike H.Int J Biol Sci. 2009;5(4):304-10. Epub 2009 Apr 16. PMID: 19381349 Free PMC Article4:Vesnarinone inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing the expression of vascular endothelial growth factor and interleukin-8. Harada K, Supriatno, Yoshida H, Sato M.Int J Oncol. 2005 Dec;27(6):1489-97. PMID: 16273203 5:A comparison of the covalent binding of clozapine, procainamide, and vesnarinone to human neutrophils in vitro and rat tissues in vitro and in vivo. Gardner I, Popović M, Zahid N, Uetrecht JP.Chem Res Toxicol. 2005 Sep;18(9):1384-94. PMID: 16167830 6:Vesnarinone-mediated alterations of gene expression in cardiac fibroblasts from aortic regurgitant hearts. Truter SL, Dumlao TF, Lee JA, Lee E, Supino PG, Borer JS.Am J Ther. 2004 Sep-Oct;11(5):328-36. PMID: 15356428 7:Precautions for use and adverse effects of vesnarinone: potential mechanisms and future therapies. Bertolet BD.Drug Saf. 2004;27 Suppl 1:11-8. Review. PMID: 15293849 8:Clinical characteristics of vesnarinone. Feldman AM.Drug Saf. 2004;27 Suppl 1:1-9. Review. PMID: 15293848 9:The best of times, the worst of times: the wealth and poverty of heart failure pharmacotherapies: is there a role for vesnarinone? Young JB.Drug Saf. 2004;27 Suppl 1:3 p following table of contents. No abstract available. PMID: 15293847 10:Extended application of an LC-MS/MS method for the analysis of vesnarinone and its metabolites in human urine and dialysate fluid. Sekar KS, Bramer SL.J Pharm Biomed Anal. 2003 Nov 24;33(4):711-7. PMID: 14623597