Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy

High Throughput Screening (HTS) is a successful strategy for finding hits and leads that have the opportunity to be converted into drugs. In this paper we highlight novel computational methods used to select compounds to build a new screening file at Pfizer and the analytical methods we used to assess their quality. We also introduce the novel concept of molecular redundancy to help decide on the density of compounds required in any region of chemical space in order to be confident of running successful HTS campaigns

Variolins and related alkaloids

Variolin B, a novel marine alkaloid that was isolated from the rare and difficult-to-access, Antarctic sponge Kirkpatrickia varialosa by the group of Blunt and Munro, is a cyclin-dependent kinases (CDK). despite their modest size, the variolins presented a challenge in their structural elucidation because of the presence of several ring-nitrogen atoms and relatively few hydrogen atoms in the structure. Hernandez Franco and Palermo reported the isolation of five 3-(2-aminopyrimidine)indoles, which were named meridianins A-E from the tunicate Apidium meridianum which has been collected at a depth of 100 m near the South Georgia Islands. The aplicyanin family was isolated from the Antarctic tunicate Aplidium cyaneum and consists of six variants on a core 3-(tetrahydropyrimidyl) indole structure. Kuhn and co-workers used their modeling software SLIDE to identify variolin B as the top candidate for the inhibition of the AsnRS found in Brugia malayi.Scott R. Walker, Erin J. Carter, Belinda C. Huff, and Jonathan C. Morri