Current Medicinal Chemistry - Volume 16, Issue 31, 2009

The wealth of biological screening data that is generated poses substantial problems to medicinal chemistry. A key question becomes how to best prioritize and select hits for further evaluation from the many weakly active compounds that are typically identified in HTS campaigns. Such decisions can be substantially supported if it is possible to evaluate preliminary structure-activity relationship (SAR) information that mig Read More

Apoptosis is strictly connected to the pathogenesis of many human diseases, including neoplastic, neurodegenerative or cardiovascular diseases. It is a highly programmed cell death which can be activated by various factors. Mitochondria play a key role in the apoptotic process; their damage, which involves permeabilization of the outer mitochondrial membrane, activates a series of events that lead to cell death. Of the two pr Read More

Human cytochrome P450 1A2 (CYP1A2) is one of the major CYPs in the liver (&sim13%) and metabolizes about 20% of clinically used drugs. CYP1A2 is a 515-residue protein with a molecular mass of 58,294 Dal. The recently published crystal structure of CYP1A2 in complex with α-naphthoflavone has showed a rather compact active site with a relatively small volume of the cavity of 375 Å3, which is 44.2% and 49.3 Read More