Novel enhancers of guanylyl cyclase-A activity acting via allosteric modulation.

ABSTRACT:

Background and purpose

Guanylyl cyclase-A (GC-A), activated by endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plays an important role in the regulation of cardiovascular and renal homeostasis and is an attractive drug target. Even though small molecule modulators allow oral administration and longer half-life, drug targeting of GC-A has so far been limited to peptides. Thus, in this study we aimed to develop small molecular activators of GC-A.

Experimental approach

Hits were identified through high-throughput screening and optimized by in silico design. Cyclic GMP was measured in QBIHEK293A cells expressing GC-A, GC-B or chimerae of the two receptors using AlphaScreen technology. Binding assays were performed in membrane preparations or whol

SUBMITTER: Andresen H 

PROVIDER: S-EPMC10952227 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature