Literature DB >> 21859304

Target repurposing for neglected diseases.

Michael P Pollastri1, Robert K Campbell.   

Abstract

Infectious diseases are an enormous burden to global health and ,since drug discovery is costly, those infectious diseases that affect the developing world are often not pursued by commercial drug-discovery efforts. Therefore, pragmatic means by which new therapeutics can be discovered are needed. One such approach is target repurposing, where pathogen targets are matched with homologous human targets that have been pursued for drug discovery for other indications. In many cases, the medicinal chemistry, structural biology and biochemistry knowledge around these human targets can be directly repurposed to launch and accelerate new drug-discovery efforts against the pathogen targets. This article describes the overarching strategy of target repurposing as a tool for initiating and prosecuting neglected disease drug-discovery programs, highlighting this approach with three case studies.

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Year:  2011        PMID: 21859304      PMCID: PMC3160716          DOI: 10.4155/fmc.11.92

Source DB:  PubMed          Journal:  Future Med Chem        ISSN: 1756-8919            Impact factor:   3.808


  40 in total

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2.  Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1.

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Journal:  Nature       Date:  1989-02-16       Impact factor: 49.962

Review 4.  Current situation of African trypanosomiasis.

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Journal:  Acta Trop       Date:  1993-09       Impact factor: 3.112

5.  Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease.

Authors:  J Erickson; D J Neidhart; J VanDrie; D J Kempf; X C Wang; D W Norbeck; J J Plattner; J W Rittenhouse; M Turon; N Wideburg
Journal:  Science       Date:  1990-08-03       Impact factor: 47.728

6.  Rational design of peptide-based HIV proteinase inhibitors.

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Journal:  Science       Date:  1990-04-20       Impact factor: 47.728

Review 7.  Polyamines as targets for therapeutic intervention.

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Journal:  Annu Rev Pharmacol Toxicol       Date:  1995       Impact factor: 13.820

8.  ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans.

Authors:  D J Kempf; K C Marsh; J F Denissen; E McDonald; S Vasavanonda; C A Flentge; B E Green; L Fino; C H Park; X P Kong
Journal:  Proc Natl Acad Sci U S A       Date:  1995-03-28       Impact factor: 11.205

9.  L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor.

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Journal:  J Med Chem       Date:  1994-10-14       Impact factor: 7.446

10.  Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes.

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Journal:  J Pharmacol Exp Ther       Date:  1996-04       Impact factor: 4.030

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  35 in total

1.  Pharmacological validation of Trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness.

Authors:  Nicholas D Bland; Cuihua Wang; Craig Tallman; Alden E Gustafson; Zhouxi Wang; Trent D Ashton; Stefan O Ochiana; Gregory McAllister; Kristina Cotter; Anna P Fang; Lara Gechijian; Norman Garceau; Rajiv Gangurde; Ron Ortenberg; Mary Jo Ondrechen; Robert K Campbell; Michael P Pollastri
Journal:  J Med Chem       Date:  2011-11-08       Impact factor: 7.446

2.  Chalcones as a basis for computer-aided drug design: innovative approaches to tackle malaria.

Authors:  Marilia Nn Lima; Bruno J Neves; Gustavo C Cassiano; Marcelo N Gomes; Kaira Cp Tomaz; Leticia T Ferreira; Tatyana A Tavella; Juliana Calit; Daniel Y Bargieri; Eugene N Muratov; Fabio Tm Costa; Carolina Horta Andrade
Journal:  Future Med Chem       Date:  2019-09-26       Impact factor: 3.808

3.  Evaluation of pyrrolidine and pyrazolone derivatives as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).

Authors:  Emanuele Amata; Nicholas D Bland; Robert K Campbell; Michael P Pollastri
Journal:  Tetrahedron Lett       Date:  2015-05-20       Impact factor: 2.415

4.  Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs.

Authors:  Stefan O Ochiana; Alden Gustafson; Nicholas D Bland; Cuihua Wang; Michael J Russo; Robert K Campbell; Michael P Pollastri
Journal:  Bioorg Med Chem Lett       Date:  2012-02-09       Impact factor: 2.823

5.  Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs.

Authors:  Cuihua Wang; Trent D Ashton; Alden Gustafson; Nicholas D Bland; Stefan O Ochiana; Robert K Campbell; Michael P Pollastri
Journal:  Bioorg Med Chem Lett       Date:  2012-02-09       Impact factor: 2.823

6.  Repurposing human PDE4 inhibitors for neglected tropical diseases: design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors.

Authors:  Emanuele Amata; Nicholas D Bland; Charles T Hoyt; Luca Settimo; Robert K Campbell; Michael P Pollastri
Journal:  Bioorg Med Chem Lett       Date:  2014-07-30       Impact factor: 2.823

7.  Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).

Authors:  Jennifer L Woodring; Nicholas D Bland; Stefan O Ochiana; Robert K Campbell; Michael P Pollastri
Journal:  Bioorg Med Chem Lett       Date:  2013-08-21       Impact factor: 2.823

8.  New chemical scaffolds for human african trypanosomiasis lead discovery from a screen of tyrosine kinase inhibitor drugs.

Authors:  Ranjan Behera; Sarah M Thomas; Kojo Mensa-Wilmot
Journal:  Antimicrob Agents Chemother       Date:  2014-01-27       Impact factor: 5.191

9.  The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing.

Authors:  Stefan O Ochiana; Vidya Pandarinath; Zhouxi Wang; Rishika Kapoor; Mary Jo Ondrechen; Larry Ruben; Michael P Pollastri
Journal:  Eur J Med Chem       Date:  2012-07-31       Impact factor: 6.514

10.  Kinase scaffold repurposing for neglected disease drug discovery: discovery of an efficacious, lapatinib-derived lead compound for trypanosomiasis.

Authors:  Gautam Patel; Caitlin E Karver; Ranjan Behera; Paul J Guyett; Catherine Sullenberger; Peter Edwards; Norma E Roncal; Kojo Mensa-Wilmot; Michael P Pollastri
Journal:  J Med Chem       Date:  2013-05-03       Impact factor: 7.446

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