The discovery of Isentress, the first in class HIV integrase inhibitor: from hit to drug

By Summa, Vincenzo
Edited By:Marcantoni, Enrico; Renzi, Gabriele
From Seminars in Organic Synthesis, “A. Corbella” Summer School, 35th, Gargnano, Italy, June 14-18, 2010 (2010), 247-268. Language: English, Database: CAPLUS

A review. A project done as part of an outstanding collaboration between scientists at IRBM in Rome and at Merck Research Labs. in West Point, Pennsylvania was described. Particularly, new class of compds. against HIV-Integrase was assessed. Due to its excellent potency, compd. 27 was further profiled in vitro and in vivo expts. When tested on an extensive panel of receptor and ion channel binding and enzyme inhibition assays it showed no significant activity. It was fully profiled in pharmacokinetic and safety studies on preclin. species, and advanced into clinic as MK-0518 to ultimately become Raltegravir or Isentress. Raltegravir met all preclin. criteria to be considered a very effective and safe HIV agent; the prediction of human PK provided the hypothesis that it would be a BID drug which was later confirmed in clin. studies. Isentress is currently used both in the first line and salvage therapies.