RP-1551s, a family of azaphilones produced by Penicillium sp., inhibit thebinding of PDGF to the extracellular domain of its receptor

Nine azaphilones designated RP-1551-1, -2, -3, -4, -5, -6, -7, -M1, and -M2 were isolated from the culture broth of Penicillium sp. SPC-21609 as inhib itors of PDGF binding to its receptor. RP-1551s inhibit the binding of PDGF AA to the extracellular domain of PDGF alpha-receptor with IC50 values ran ging from 0.1 to 2 mu M without affecting PDGF BE binding to the extracellu lar domain of PDGF beta-receptor. PDGF binding was not restored after the P DGF alpha-receptor extracellular domain was washed in an attempt to remove the RP-1551-1 bound to the receptor. This result suggests that RP-1551-1 ma y irreversibly interact with the PDGF alpha-receptor. Since many azaphilone compounds possess high reactivity with an amino group, RP-1551-1 may preve nt PDGF AA binding by reacting with amino groups on the alpha-receptor extr acellular domain.