Post-doctoral Fellow, UCSD
Skaggs School of Pharmacy and Pharmaceutical Sciences
Neglected tropical diseases (NTDs) are a group of infections that disproportionately affect the developing world and often keep people from escaping extreme poverty. Current therapies are lacking with many suffering from issues of toxicity and drug resistance.
My research focuses on lead identification and development of clinical candidates through drug-repurposing efforts. This is a multidisciplinary approach to develop new therapies for neglected tropical diseases, namely for inhibitors to Trypanosoma brucei.
By screening drug libraries we can elucidate potential chemotypes with lead-like properties for further development. Using a combination of medicinal chemistry, in vitro testing of compound efficacy and in vivo pharmacokinetics we can probe for structure-activity relationships (SAR) and further optimize compound in vivo activity and physical properties.
Discovery libraries targeting the major enzyme classes: the serine hydrolases. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3807-13. doi: 10.1016/j.bmcl.2014.06.063. Epub 2014 Jun 27. Otrubova K, Srinivasan V, Boger DL.
alpha-Ketoheterocycle inhibitors of fatty acid amide hydrolase: exploration of conformational constraints in the acyl side chain. Bioorg Med Chem. 2014 May 1;22(9):2763-70. doi: 10.1016/j.bmc.2014.03.013. Epub 2014 Mar 18. Duncan KK, Otrubova K, Boger DL.
Design, synthesis, and characterization of alpha-ketoheterocycles that additionally target the cytosolic port Cys269 of fatty acid amide hydrolase. J Med Chem. 2014 Feb 13;57(3):1079-89. doi: 10.1021/jm401820q. Epub 2014 Jan 23. Otrubova K, Cravatt BF, Boger DL.
Potent vinblastine C20' ureas displaying additionally improved activity against a vinblastine-resistant cancer cell line. ACS Med Chem Lett. 2013 Sep 9;4(10). doi: 10.1021/ml400281w. Barker TJ, Duncan KK, Otrubova K, Boger DL.
Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues. J Am Chem Soc. 2013 Apr 24;135(16):6289-99. doi: 10.1021/ja4014997. Epub 2013 Apr 12. Otrubova K, Brown M, McCormick MS, Han GW, O'Neal ST, Cravatt BF, Stevens RC, Lichtman AH, Boger DL.
alpha-Ketoheterocycle-based Inhibitors of Fatty Acid Amide Hydrolase (FAAH). ACS Chem Neurosci. 2012 May 16;3(5):340-348. Epub 2011 Dec 20. Otrubova K, Boger DL.
The discovery and development of inhibitors of fatty acid amide hydrolase (FAAH). Bioorg Med Chem Lett. 2011 Aug 15;21(16):4674-85. doi: 10.1016/j.bmcl.2011.06.096. Epub 2011 Jun 28. Review. Otrubova K, Ezzili C, Boger DL.
Fatty acid amide signaling molecules. Bioorg Med Chem Lett. 2010 Oct 15;20(20):5959-68. doi: 10.1016/j.bmcl.2010.08.048. Epub 2010 Aug 13. Review. Ezzili C, Otrubova K, Boger DL.
Comprehensive study of sansalvamide A derivatives and their structure-activity relationships against drug-resistant colon cancer cell lines. J Med Chem. 2008 Feb 14;51(3):530-44. doi: 10.1021/jm070731a. Epub 2008 Jan 11. Otrubova K, Lushington G, Vander Velde D, McGuire KL, McAlpine SR.
Scaffold targeting drug-resistant colon cancers. J Med Chem. 2007 May 3;50(9):1999-2002. Epub 2007 Apr 6. Otrubova K, McGuire KL, McAlpine SR.
Synthesis of second-generation sansalvamide A derivatives: novel templates as potential antitumor agents. J Org Chem. 2007 Mar 16;72(6):1980-2002. Epub 2007 Feb 22. Rodriguez RA, Pan PS, Pan CM, Ravula S, Lapera S, Singh EK, Styers TJ, Brown JD, Cajica J, Parry E, Otrubova K, McAlpine SR.
Synthesis of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29. Bioorg Med Chem. 2006 Aug 15;14(16):5625-31. Epub 2006 May 11. Styers TJ, Kekec A, Rodriguez R, Brown JD, Cajica J, Pan PS, Parry E, Carroll CL, Medina I, Corral R, Lapera S, Otrubova K, Pan CM, McGuire KL, McAlpine SR.
Synthesis and novel structure-activity relationships of potent sansalvamide A derivatives. Chem Commun (Camb). 2006 Mar 7;(9):1033-4. Epub 2006 Feb 1. Otrubova K, Styers TJ, Pan PS, Rodriguez R, McGuire KL, McAlpine SR.