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SIGA Technologies, Inc. Message Board

  • amlnlover100 amlnlover100 Mar 5, 2013 10:30 PM Flag

    Back to the Future: Ol' ST-610 is the Latest and Greatest

    Antimicrob. Agents Chemother. Published ahead of print 12 February 2013
    A Novel Benzoxazole Inhibitor of Dengue Virus Replication that Targets the NS3 Helicase
    Chelsea M. Byrd1, Douglas W. Grosenbach1, Aklile Berhanu1, Dongcheng Dai1, Kevin F. Jones1, Kara B. Cardwell1, Christine Schneider1, Guang Yang1, Shanthakumar Tyavanagimatt1, Chris Harver1, Kristin A. Wineinger1, Jessica Page1, Eric Stavale1, Melialani A. Stone1, Kathleen P. Fuller1, Candace Lovejoy1, Janet M. Leeds1, Dennis E. Hruby1 and Robert Jordan1

    "...Here we report the results of a high-throughput screen of a chemical compound library using a whole virus assay, that identified a novel small molecule inhibitor of DENV, ST-610, that potently and selectively inhibits all four serotypes of DENV replication in vitro. Sequence analysis of drug-resistant virus isolates has identified a single-point mutation, A263T, in the NS3 helicase domain that confers resistance to the compound. ST-610 inhibits DENV NS3 helicase RNA unwinding activity in a molecular beacon-based helicase assay, but does not inhibit nucleoside triphosphatase activity based on a malachite green ATPase assay. ST-610 is non-mutagenic, well-tolerated (non-toxic) in mice, and has shown efficacy in a sub-lethal murine model of DENV infection with the ability to significantly reduce viremia and viral load compared to vehicle controls."

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    • More recent papers:

      Antimicrob Agents Chemother. 2013 Feb 12. [Epub ahead of print]
      A Novel Benzoxazole Inhibitor of Dengue Virus Replication that Targets the NS3 Helicase.
      Byrd CM, Grosenbach DW, Berhanu A, Dai D, Jones KF, Cardwell KB, Schneider C, Yang G, Tyavanagimatt S, Harver C, Wineinger KA, Page J, Stavale E, Stone MA, Fuller KP, Lovejoy C, Leeds JM, Hruby DE, Jordan R.

      Bioorg Med Chem Lett. 2013 Feb 1;23(3):750-6. doi: 10.1016/j.bmcl.2012.11.093. Epub 2012 Dec 1.
      Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles.
      Burgeson JR, Moore AL, Gharaibeh DN, Larson RA, Cerruti NR, Amberg SM, Hruby DE, Dai D.

      Bioorg Med Chem Lett. 2013 Feb 1;23(3):744-9. doi: 10.1016/j.bmcl.2012.11.095. Epub 2012 Dec 1.
      Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole.
      Dai D, Burgeson JR, Gharaibeh DN, Moore AL, Larson RA, Cerruti NR, Amberg SM, Bolken TC, Hruby DE.

      Antimicrob Agents Chemother. 2013 Mar;57(3):1136-43. doi: 10.1128/AAC.00959-12. Epub 2012 Dec
      Pharmacokinetic and Pharmacodynamic Modeling To Determine the Dose of ST-246 To Protect against Smallpox in Humans.
      Leeds JM, Fenneteau F, Gosselin NH, Mouksassi MS, Kassir N, Marier JF, Chen Y, Grosenbach D, Frimm AE, Honeychurch KM, Chinsangaram J, Tyavanagimatt SR, Hruby DE, Jordan R.

      Antimicrob Agents Chemother. 2013 Jan 57(1):15-25. doi: 10.1128/AAC.01429-12. Epub 2012 Oct 15.
      A novel inhibitor of dengue virus replication that targets the capsid protein.
      Byrd CM, Dai D, Grosenbach DW, Berhanu A, Jones KF, Cardwell KB, Schneider C, Wineinger KA, Page JM, Harver C, Stavale E, Tyavanagimatt S, Stone MA, Bartenschlager R, Scaturro P, Hruby DE, Jordan R.

    • Too technical for me. Especially good news?

    • Taken from the SIGA 10-K filed Mar 6, 2009: "Compounds from two of these series have recently shown efficacy in a murine model of disease, including ST-610"

      I thought we were waiting for the release of data on newer and better candidates?

 
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