The effects of diminishing albumin binding to some Endothelin receptor antagonists.
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Szczepankiewicz BG, Bal RB, von Geldern TW, Wu-Wong JR, Chiou WJ, Dixon DB, Opgenorth TJ, Hoffman DJ, Borre AJ, Marsh KC, Nguyen BN
The effects of diminishing albumin binding to some Endothelin receptor antagonists.
Life Sci. 1998;63(21):1905-12. doi: 10.1016/s0024-3205(98)00466-4.
- PubMed ID
- 9825768 [ View in PubMed]
- Abstract
As a pharmacological class, Endothelin-A receptor (ET(A)) antagonists are highly bound (>98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET(A) decrease 10 to 100 fold. We have prepared ET(A) antagonists which exhibit lower degrees of binding to albumin, while maintaining potency and selectivity for the ET(A) receptor. The protein induced IC50 shift is reduced or eliminated in this new series of compounds. The compounds also display altered in vivo and pharmacokinetic profiles which may be consistent with their lower degree of protein binding.