Salter, E. A. published the artcileHomology models of the catalytic sites of phosphodiesterase 5A and 10A and molecular docking of selective apoptotic antineoplastic drugs (SAANDs), Formula: C20H17FO4S, the publication is International Journal of Quantum Chemistry (2004), 96(4), 402-410, database is CAplus.
Achieving selective inhibition for individual gene families of cyclic nucleotide phosphodiesterases (CNPDE) isoenzymes has become an important pharmacol. goal now that the diversity of these hydrolases has been recognized. Selective apoptotic antineoplastic drugs (SAANDs) induce apoptosis in neoplastic cells and not in normal cells by a mechanism involving inhibition of overexpressed PDEs that hydrolyze cyclic GMP. SAANDs, although not selective, show a preference for PDE5 and PDE10. However, highly selective PDE5 inhibitors do not induce apoptosis. To study differences in PDE inhibitors, we constructed homol. models of the target catalytic domains of PDE5A and PDE10A based upon the X-ray crystal structure of the catalytic domain of PDE4B. Mol. mechanics docking is planned to define new SAANDs vs. ineffective agents. We investigated the binding of exisulind (Aptosyn) and other analogs to PDE4, 5, and 10 isoforms using our mol. models and compared the resultant estimated binding energies with exptl. IC50 values. Proposed binding orientations for CP 248, a higher-affinity and more selective inhibitor of PDE5 and PDE10 than exisulind, are presented. The modeling studies described here allowed us to identify some differing structural features of the catalytic pockets that may be helpful in the development of active and more selective drugs to treat tumors found in different tissues while maintaining minimal side effects.
International Journal of Quantum Chemistry published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Formula: C20H17FO4S.
Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem