PCOL 826A Final Exam: PDE inhibitors
Questions with Complete Solutions superfamily of enzymes that degrade secondary messengers cAMP and cGMP - Correct Answers ✅Phosphodiesterases (PDE) PDEs are targets for the treatment of ___ failure, ___, ____, ___, ____ dysfunction, and ___ indications - Correct Answers ✅heart; depression; asthma; inflammation; erectile; and CNS cAMP specific (auto-immune indications) - Correct Answers
✅PDE4
cGMP (corpus cavernosum tissue) - Correct Answers
✅PDE5
how many enzymes are in the PDE family? - Correct Answers ✅11 PDE4 prevents formation of ____ and PDE5 prevents formation of ___ - Correct Answers ✅5'-AMP; 5'-GMP what is the key structural biology point for PDEs? - Correct Answers ✅invariant glutamine invariant glutamine has pivotal ___ and ___ interaction for ___ and ____ - Correct Answers ✅donor; acceptor; PDE4; PDE5 1 / 2
PCOL 826A Final Exam: PDE inhibitors
Questions with Complete Solutions invariant glutamine is a ____ target reside for the ___ of the majority of ___ inhibitors - Correct Answers ✅fundamental; majority; PDE cilomilast - Correct Answers ✅PDE4 inhibitor (Ki = 20 nM) piclamilast - Correct Answers ✅PDE4 inhibitor (Ki = 1 nM) cilomilast goal is ___ in production of pro-inflammatory cytokine ____ - Correct Answers ✅reduction; TNF-a
PDE4 4-point pharmacophore - Correct Answers ✅green:
hydrophobic pocket
blue: catechol (2 interactions w invariant glutamine)
purple: metal binding (Zn2+)
the interaction with ____ holds ____ and the ___ in place in a ___ fashion - Correct Answers ✅Gln466; cyclopentane; catechol; bidentate Gln 466 H-bond interaction with PDE4 - Correct Answers ✅O is an acceptor
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