Pharmacophore discovery--lessons learned.
Pharmacophore discovery is one of the major elements of molecular modeling in the absence of X-ray structural data. While pharmacophores initially made their debut as a means for lead discovery, more recent refinements have brought them into the domain of lead optimization, e.g. as a means to define the molecular alignment in 3D-QSAR. In this review, the experiences of over a decade of confronting and solving the challenges of pharmacophore discovery applied to actual drug discovery are summarized. Also, practical tips are described for using the author's methodology for pharmacophore discovery, DANTE.
van Drie
John H
JH
Vertex Pharmaceuticals, 130 Waverly St., Cambridge, MA 02139, USA. vandrie@mindspring.com
D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship