Preclinical and Clinical Profile of HIV-1 Integrase Strand-transfer Inhibitor GS-9224 Compared to its Parent Compound GS-9160

Abstract

Materials and Methods Compounds GS-9224 and GS-9160 were synthesized at Gilead Sciences, Inc. L-870,810 was synthesized by Combi Blocks, Inc. (San Diego, CA). RAL was synthesized by Naeja Pharmaceuticals, Inc. (Edmonton, Alberta Canada). All three compounds have a purity of >95% as determined by analytical reversed phase HPLC using a Phenomenex Luna C18 column and UV detection at 214 nm and 254 nm. The structures of these three INSTIs are shown in (Figure 1). Cells MT-2 cells were obtained from Stanford University and MT-4 cells were obtained from the NIH AIDS Research and Reference Reagent Program (Germantown, MD). SupT1 cells were obtained from the American Type Culture Collection (Rockville, MD). MT-2, MT-4 and SupT1 cells were maintained in RPMI-1640 medium (Cat # 61870