title: Identification of two HIV inhibitors that also inhibit human RNaseH2.
abstract: A total of 140,000 compounds were screened in a targetfree cell-based high throughput assay against HIV-1 infection, and a subset of 81 promising compounds was identified. Secondary screening of these 81 compounds revealed two putative human RNaseH2 inhibitors, RHI001 and RHI002, with IC50 value of 6.8 μM and 16 μM, respectively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 μM, 7.9 μM, and 31.7 μM, respectively. Kinetic analysis revealed that both inhibitors had non-competitive inhibitor-like properties. Because RNaseH2 is involved in the etiology of Aicardi-Goutier syndrome and has been suggested as an anticancer drug target, small molecule inhibitors modulating its activity would be useful for investigating the cellular function of this molecule.
authors.affiliation: Drug Biology Group, Institut Pasteur Korea, Seongnam, 463-400, Korea.
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Jaewan
authors.initials: J
authors.lastname: Yoon
authors.forename: MoonKyeong
authors.initials: M
authors.lastname: Ju
authors.forename: Yunmi
authors.initials: Y
authors.lastname: Lee
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Kim
authors.forename: Junwon
authors.initials: J
authors.lastname: Kim
authors.forename: Peter
authors.initials: P
authors.lastname: Sommer
authors.forename: Zaesung
authors.initials: Z
authors.lastname: No
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cechetto
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Han
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D020274:Autoimmune Diseases of the Nervous System / Q000188:drug therapy / Q000209:etiology; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D015394:Molecular Structure; D009421:Nervous System Malformations / Q000188:drug therapy / Q000209:etiology; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054309:Ribonuclease H, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors; D012260:Ribonucleases; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D011743:Pyrimidines; C587780:RHI001; C587781:RHI002; D013876:Thiophenes; D012260:Ribonucleases; C091139:ribonuclease HII; D016914:Ribonuclease H; D054309:Ribonuclease H, Human Immunodeficiency Virus; C078856:ribonuclease HI