HIV integrase

7 jjlM measured with Hela cells). Nevertheless, the lamellarins have an intrinsic potential for the inhibition of HIV-1 integrase. But so far this pharmacological activity has not been thoroughly explored. 

Molecules Cell lines Time incubation Test IC50 Reference 

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Chee MS, Bankeir AT, Beck S, Bohni R, Brown CM, Cerny R, Horsnel T, Hutchinson CAI, Kouzarides T, Martignetti JA, Preddie E, Satchwell SP, Tomlinson P, Weston KM, Barrel BG (1990) Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169, Curr Top Microbiol Immunol 154 125-170 Chiu TK, Davies DR (2004) Structure and function of HIV-1 integrase. Curr Top Med Chem 4 965-977... 

Underwood M, Harvey R, Stanat S, Hemphill M, Miller T, Drach J, Townsend L, Biron K (1998) Inhibition of human cytomegalovirus DNA maturation by a benzimidazole ribonucleoside is mediated through the UL89 gene product. J Virol 72 717-725 Van Maele B, Debyser Z (2005) HlV-1 integration an interplay between HIV-1 integrase, cellular, and viral proteins. AIDS Rev 7 26 3... 

HIV-1 integrase inhibitors, IC50 3 -processing = 0.6 pg/ml, IC50 strand transfer = 0.46 pg/ml... 

HIV-1 integrase inhibitor, 1C50 3 -processing = 17 pM, IC50 strand transfer = 11 pM... 

Hong H, Neamati N, Wang S, Nicklaus MC, Mazumder A, Zhao H, Burke Jr TR, Pommier Y, Milne GWA. Discovery of HIV-1 integrase inhibitors by pharmacophore searching. J Med Chem 1997 40 930-6. 

Dayam R, Sanchez T, Clement O, Shoemaker R, Sei S, Neamati N. P-Diketo acid pharmacophore hypothesis. 1. Discovery of a novel class of HIV-1 integrase inhibitors. J Med Chem 2005 48 111-20. 

HIV-1 integrase strand transfer inhibitors, 45, 263 HIV prevention strategies, 40, 277 HIV protease inhibitors, 26,141 29, 123 HIV reverse transcriptase inhibitors, 29,123 HIV therapeutics, 40, 291 HIV vaccine, 27, 255... 

Metal ions are required for the activity of anti-HIV G-quartet oligonucleotides (antisense oligonucleotides) such as T30177, a potent inhibitor of the enzyme HIV-1 integrase. 

Inhibition of HIV-1 Integrase 3 Processsing (3 -Proc), Strand Transfer (ST) and HIV-1RF Cytopathicity (HIV-1rf) by Some Guanine Quartets in Cell Cultures... 

Milne et al. described the discovery of HIV-1 protease inhibitors based on a pharmacophore derived from X-ray crystal structures. After searching the NCI database with 206 000 entries and postfiltering the resulting hits, a total of 50 molecules were tested, leading to submicromolar activity for the best two compounds [286]. In their search for HIV-1 integrase inhibitors, another pharmacophore produced up to 340 hits, resulting in 10 structurally different classes and four compounds with affinities below 30 XM [287]. 

Di-caffeoylquinic acid (70) Cyclic polyolic derivative 1,5-DCQA(70) Antiviral (Anti-HIV HIV/AIDS and hepatitis B) Inhibits HIV-1 integrase Phase l/Il Chinese Academy of Military Medical Sciences 583-585... 

Liao, C.Z., Karki, R.G., Marchand, C., Pommier, Y., Nicklaus, M.C. Virtual screening application of a model of full-length HIV-1 integrase complexed with viral DNA. Bioorg. Med. Chem. Lett. 2007, 17, 5361-5. 

Kim, H.J. et al., A new flavonol glycoside gallate ester from Acer okamotoanum and its inhibitory activity against HIV-1 integrase, J. Nat. Prod., 61, 145, 1998. 

Several lines of evidence demonstrate that the active unit of integrase is a multimer. It is clear, as an isolated protein in solution, that integrase forms dimers [6,10-12], and it has been shown by sedimentation equilibrium studies that Rous sarcoma virus (RS V) integrase exists in reversible equilibrium between monomeric, dimeric, and tetrameric forms [13]. Protein-protein cross-linking studies of HIV-1 [14] and RSV [15] integrases confirm the existence of protein dimers and tetramers in solution, and in vivo, the yeast GAL4 two-hybrid system has demonstrated that HIV-1 integrase can interact with itself [16]. 

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