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The challenges of developing novel antiparasitic drugs

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  • Published:
Invertebrate Neuroscience

Abstract

Only a few novel classes of antiparasitic drugs have emerged over the last few decades, reflecting the difficulties associated with bringing a safe, effective molecule to market. In recent years, the screening paradigm has shifted from empirical whole parasite screening towards mechanism-based high throughput screening. This approach requires investment in molecular parasitology and in understanding the basic biology of parasites, as well as requiring considerable investment in an infrastructure for screening. Add to this the fact that the drug discovery process is iterative with high attrition, the Animal Health industry by necessity must focus on discovering medicines for diseases, which will deliver a return on investment. In recent years the rapid progression of genomics has unlocked a plethora of tools for target identification, validation and screening, revolutionising mechanism-based screening for antiparasitic drug discovery. The challenge still remains; however, to identify novel chemical entities with the properties required to deliver a safe, effective antiparasitic drug.

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References

  • Aboobaker AA, Blaxter M (2003) Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi. Mol Biochem Parasitol 129:41–51

    Article  PubMed  CAS  Google Scholar 

  • Adams M et al (2000) The Genome sequence of Drosophila melanogaster. Science 287:2185–2195

    Article  PubMed  Google Scholar 

  • Behm CA, Bendig MM, McCarter JP, Sluder AE (2005) RNAi-based discovery and validation of new drug targets in filarial nematodes. Trends Parasitol. 21:97–100

    Article  PubMed  CAS  Google Scholar 

  • Beno BR, Mason JS (2001) The design of combinatorial libraries using properties and 3D pharmacophore fingerprints. Drug Discov Today 6:251–258

    Article  PubMed  CAS  Google Scholar 

  • Brand AH, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118:401–415

    PubMed  CAS  Google Scholar 

  • C.elegans Sequencing Consortium (1998) Genome Sequence of the Nematode C.elegans: A Platform for Investigating Biology. Science 282:2012–2018

    Article  Google Scholar 

  • Campbell WC (1993) Ivermectin, an antiparasitic agent. Med Res Rev 13:61–79

    Article  PubMed  CAS  Google Scholar 

  • Carr R, Hann M (2002) The right road to drug discovery? Mod Drug Discov 5:45–48

    Google Scholar 

  • Chintapalli VR, Wang J, Dow JAT (2007) Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat Genet 39:715–720

    Article  PubMed  CAS  Google Scholar 

  • Cowman AF, Crabb BS (2003) Functional genomics: identifying drug targets for parasitic diseases. Trends Parasitol 19:538–541

    Article  PubMed  CAS  Google Scholar 

  • Dow JAT (2007) Integrative physiology, functional genomics and the phenotype gap: a guide for comparative physiologists. J Exp Biol 210:1632–1640

    Article  PubMed  Google Scholar 

  • Dow JAT, Davies SA (2003) Integrative physiology and functional genomics of epithelial function in a genetic model organism. Physiol Rev 83:687–729

    PubMed  CAS  Google Scholar 

  • Dow JAT, Davies SA (2006). The Malpighian tubule: rapid insights from post-genomic biology. J Insect Physiol 52:365–378

    Article  PubMed  CAS  Google Scholar 

  • Evans JM, Allan AK, Davies SA, Dow JAT (2005) Sulphonylurea sensitivity and enriched expression implicate inward rectifier K+ channels in Drosophila melanogaster renal function. J Exp Biol 208:3771–3783

    Article  PubMed  CAS  Google Scholar 

  • Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811

    Article  PubMed  CAS  Google Scholar 

  • Frye SV (1999) Structure-activity relationship homology (SARAH): a conceptual framework for drug discovery in the genomic era. Chem Biol 6:R3–R7

    Article  PubMed  CAS  Google Scholar 

  • Geary TG, Thompson DP, Klein RD (1999) Mechanism-based screening: discovery of the next generation of anthelmintics depends upon more basic research. Int J Parasitol 29:105–112

    Article  PubMed  CAS  Google Scholar 

  • Geary TG, Conder GA, Bishop (2004) The changing landscape of antiparasitic drug discovery in veterinary medicine. Trends Parasitol 20:449–455

    Article  PubMed  CAS  Google Scholar 

  • Geldhof P, Visser A, Clark D, Saunders G, Britton C, Gilleard J, Berriman M, Knox D (2007) RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects. Parasitol 134:1–11

    Article  Google Scholar 

  • Gilleard JS, Woods DJ, Dow JAT (2005) Model-organism genomics in veterinary parasite drug-discovery. Trends Parasitol 21:302–305

    Article  PubMed  CAS  Google Scholar 

  • Hann MM, Leach AR, Harper G (2001) Molecular complexity and its impact on the probability of finding leads for drug discovery. J Chem Inf Comput Sci 41:856–864

    Article  PubMed  CAS  Google Scholar 

  • Hill CA, Wikel SK (2005) The Ixodes scapularis genome project: an opportunity for advancing tick research. Trends Parasitol 21:151–153

    Article  PubMed  CAS  Google Scholar 

  • Hopkins AL, Groom CR (2002) The druggable genome. Nat Rev Drug Discov 1:727–730

    Article  PubMed  CAS  Google Scholar 

  • Hopkins AL, Groom CR, Alexander A (2004) Ligand efficiency: a useful metric for lead selection Drug Disc. Today 9:430–431

    Google Scholar 

  • Hopkins AL, Witty MJ, Nwaka S (2007) Mission possible. Nature 449:166–169

    Article  PubMed  CAS  Google Scholar 

  • Hussein AS, Kichenin K, Selkirk ME (2002) Suppression of secreted acetylcholinesterase expression in Nippostrongylus brasiliensis by RNA interference. Mol Biochem Parasitol 122:91–94

    Article  PubMed  CAS  Google Scholar 

  • International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  Google Scholar 

  • Lesuisse D, Lange G, Deprez P, Bènard D, Schoot B, Delettre G, Marquette J-P, Broto P, Vèronique J-B, Bichet P et al (2002) SAR and X-ray. A new approach combining fragment-based screening and rational drug design: Application to the discovery of nanomolar inhibitors of Src SH2. J Med Chem 45:2379–2387

    Article  PubMed  CAS  Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW et al (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 23:3–25

    Article  CAS  Google Scholar 

  • Londershausen M (1996) Approaches to new parasiticides. Pestic Sci 48:269–292

    Article  CAS  Google Scholar 

  • Lustigman S, Zhang J, Liu J, Oksov Y, Hashmi S (2004) RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting. Mol Biochem Parasitol 138:165–170

    Article  PubMed  CAS  Google Scholar 

  • McCarter JP (2004) Genomic filtering: an approach to discovering novel antiparasitics. Trends Parasitol 20:462–468

    Article  PubMed  CAS  Google Scholar 

  • Mongan NP, Jones AK, Smith GR, Sansom MSP, Sattelle DB (2002) Novel α7-like nicotinic acetylcholine receptor subunits in the nematode Caenorhabditis elegans. Protein Sci 11:1162–1171

    Article  PubMed  CAS  Google Scholar 

  • Nwaka S, Hudson A (2006) Innovative lead discovery strategies for tropical diseases. Nat Rev Drug Discov 5:941–955

    Article  PubMed  CAS  Google Scholar 

  • Ramakrishnan VG, Aljamali MN, Sauer JR, Essenberg RC (2005) Application of rna interference in tick salivary gland research. J Biomol Tech 16:297–305

    PubMed  Google Scholar 

  • Rees DC, Congreve M, Murray CW, Carr R (2004) Fragment-based lead discovery. Nat Rev Drug Discov 3:660–672

    Article  PubMed  CAS  Google Scholar 

  • Terrett NK, Gardner M, Gordon DW et al (1995) Combinatorial synthesis—the design of compound libraries and their application to drug discovery. Tetrahedron 51:8135–8173

    Article  CAS  Google Scholar 

  • Walters WP, Stahl MT, Murcko MA (1998) Virtual Screenings—an overview. Drug Discov Today 3:160–178

    Article  CAS  Google Scholar 

  • Wicks SR, Yeh RT, Gish WR, Waterston RH, Plasterk RHA (2001) Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nat Genet 28:160–164

    Article  PubMed  CAS  Google Scholar 

  • Witty MJ (1999) Current strategies in the search for novel antiparasitic agents. Int J Parasitol 29:95–103

    Article  PubMed  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Pfizer Animal Health, Pfizer Ltd, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK

    Debra J. Woods & Tracey M. Williams

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  1. Debra J. Woods
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  2. Tracey M. Williams
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Correspondence to Debra J. Woods.

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Woods, D.J., Williams, T.M. The challenges of developing novel antiparasitic drugs. Invert Neurosci 7, 245–250 (2007). https://doi.org/10.1007/s10158-007-0055-1

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  • DOI: https://doi.org/10.1007/s10158-007-0055-1

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