Description
Derenofylline is an adenosine A
1 receptor antagonist (K
i = 1 nM). It is selective for adenosine A
1 over A
2A, A
2B, and A
3 receptors (K
is = 398, 3,981, and 200 nM, respectively). It decreases adenosine A
1 receptor-mediated adenosine-induced bradycardia in rats (ED
50 = 0.49 mg/kg) but reduces A
2 receptor-mediated adenosine-induced hypotension by only 44.6% when administered at an intravenous dose of 5 mg/kg. It prevents increases in heart levels of collagen I and III in nephrectomized rats when administered at a dose of 10 mg/kg per day. Derenofylline also reduces relative plaque counts in a Zika virus plaque-forming assay in A549 cells (IC
50 = 58.6 nM) in an adenosine A
1 receptor-independent manner without inducing cytotoxicity when used at concentrations less than 10 μM.
References
[1] P KALK. The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure[J]. British Journal of Pharmacology, 2009, 151 7: 1025-1032. DOI:
10.1038/sj.bjp.0707319[2] EWA D. MICEWICZ . Identification of novel small-molecule inhibitors of Zika virus infection[J]. Bioorganic & Medicinal Chemistry Letters, 2018, 28 3: Pages 452-458. DOI:
10.1016/j.bmcl.2017.12.019
