Abstract: The disclosure generally relates to compounds, compositions, and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract: The disclosure generally relates to compounds, compositions, and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract: The disclosure generally relates to compounds of formulas (I) and (II)7 including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract: The disclosure generally relates to compounds of formulas (I) and (II)7 including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract: Methods to inhibit the formation of retrovirus integrase reaching dimers, to dissociate retrovirus integrase reaching dimers, and to stabilize retrovirus integrase reaching dimers in a conformation in which retrovirus DNA-to host cell DNA integration activity of the integrase is inhibited are provided. Methods for treating a retrovirus infection, which target retrovirus integrase reaching dimer formation and/or stability are also provided.

Abstract: Methods to inhibit the formation of retrovirus integrase reaching dimers, to dissociate retrovirus integrase reaching dimers, and to stabilize retrovirus integrase reaching dimers in a conformation in which retrovirus DNA-to host cell DNA integration activity of the integrase is inhibited are provided. Methods for treating a retrovirus infection, which target retrovirus integrase reaching dimer formation and/or stability are also provided.

Abstract: A high throughput RNAi-based assay for identify factors involved in maintaining epigenetic silencing is disclosed. The assay measures reactivation of a silent reporter gene in cells, resulting from RNAi-based knockdown in target mRNA. RNAi-based screening of these silent reporter cells has identified known enzymes that place or remove epigenetic marks on histones, as well as non-enzymatic proteins that function in silencing or in transfer of marks during S-phase. In addition, the screen has been used to identify a number of novel gene products involved in epigenetic silencing, which are also disclosed.

Abstract: Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.

Abstract: Cellular targets for anti-retroviral drug development are disclosed. The cellular targets comprise ATR kinase and its relevant substrates, based on the identification of the ATR kinase as required for the final step of retroviral DNA integration. Assays for identifying modulators of retroviral integration via the ATR kinase pathway are disclosed, as well as modulators identified by such assays. Pharmaceutical preparations and methods of their use in treating retroviral infection are also disclosed.

Abstract: The present invention provides novel chimeric and fusion proteins useful for facilitating site-specific integration of foreign DNA into a host genome. The chimeric enzymes of the invention comprise a DNA binding moiety fused to a retroviral integrase moiety, preferably at the precise N- or C-terminus. Nucleic acids encoding these fusion proteins can be incorporated into standard retroviral vectors, or can be provided as purified proteins. They are capable of exerting the activities of a wildtype retroviral integrase, including processing retroviral DNA termini, nicking double-stranded DNA and integrating a DNA molecule with processed retroviral termini into another DNA strand.