Angelo D. Favia

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Short-chain dehydrogenases/reductases (SDR) constitute one of the largest enzyme superfamilies with presently over 46,000 members. In phylogenetic comparisons, members of this superfamily show early divergence where the majority have only low pairwise sequence identity, although sharing common structural properties. The SDR enzymes are present in virtually(More)
Molecular recognition between proteins and their interacting partners underlies the biochemistry of living organisms. Specificity in this recognition is thought to be essential, whereas promiscuity is often associated with unwanted side effects, poor catalytic properties and errors in biological function. Recent experimental evidence suggests that(More)
Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1(More)
Mammalian cytochromes P450 (CYP) are enzymes of great biological and pharmaco-toxicological relevance. Due to their membrane-bound nature, the structural characterization of these proteins is extremely difficult, and therefore computational techniques, such as comparative modeling, may help obtaining reliable structures of members of this family. An(More)
Protein ligand docking has recently been investigated as a tool for protein function identification, with some success in identifying both known and unknown substrates of proteins. However, identifying a protein's substrate when cross-docking a large number of enzymes and their cognate ligands remains a challenge. To explore a more limited yet practically(More)
Polypharmacology-based strategies are gaining increased attention as a novel approach to obtaining potentially innovative medicines for multifactorial diseases. However, some within the pharmaceutical community have resisted these strategies because they can be resource-hungry in the early stages of the drug discovery process. Here, we report on(More)
Most function prediction methods that identify cognate ligands from binding site analyses work on the assumption of molecular complementarity. These approaches build on the conjectured complementarity of geometrical and physicochemical properties between ligands and binding sites so that similar binding sites will bind similar ligands. We found that this(More)
The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone to the active glucocorticoid cortisol, thereby acting as a cellular switch to mediate glucocorticoid action in many tissues. Several studies have indicated that 11beta-HSD1 plays a crucial role in the onset of type 2 diabetes and central obesity. As a consequence,(More)
The design, synthesis, and biological evaluation of a series of new aromatase inhibitors bearing an imidazole or triazole ring linked to a fluorene (A), indenodiazine (B), or coumarin scaffold (C) are reported. Properly substituted coumarin derivatives displayed the highest aromatase inhibitory potency and selectivity over 17-alpha-hydroxylase/17-20 lyase.(More)
Human carbonyl reductase is a member of the short-chain dehydrogenase/reductase (SDR) protein superfamily and is known to play an important role in the detoxification of xenobiotics bearing a carbonyl group. The two monomeric NADPH-dependent human isoforms of cytosolic carbonyl reductase CBR1 and CBR3 show a sequence similarity of 85% on the amino acid(More)