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Thymidylate synthase structure, function and implication in drug discovery.

M P Costi1, S Ferrari, A Venturelli

  • 1Dipartimento di Scienze Farmaceutiche, Università di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy. costimp@unimore.it

Current Medicinal Chemistry
|September 24, 2005
PubMed
Summary
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Genomics and proteomics advance drug discovery by revealing new targets like Thymidylate Synthase (TS). This enables developing novel inhibitors for cancer and infectious diseases.

Area of Science:

  • Drug discovery and medicinal chemistry
  • Enzymology and molecular biology
  • Genomics and proteomics

Background:

  • Thymidylate Synthase (TS) is a validated anti-cancer drug target, with drugs like 5-fluorouracil and ZD1694 in clinical use.
  • Traditional TS inhibitors are folate-based, limiting development of drugs targeting pathogen-specific TS enzymes.
  • Omic studies have identified Thymidylate Synthase Complementing Protein (TSCP or ThyX) in pathogens, offering a distinct structural target.

Purpose of the Study:

  • To explore novel drug targets and mechanisms of action using advanced methodologies.
  • To highlight the potential of Thymidylate Synthase (TS) as a target for both anti-cancer and anti-infective therapies.
  • To discuss the identification and potential of pathogen-specific TS enzymes, such as TSCP (ThyX), for targeted drug development.

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Main Methods:

  • Application of recent methodologies including genomics and proteomics in drug discovery.
  • Analysis of biological pathways involving Thymidylate Synthase (TS).
  • Investigation of enzyme structures to identify unique target domains for pathogen-specific inhibition.

Main Results:

  • Genomics and proteomics have enhanced the understanding of drug action and identified new drug targets.
  • Improved knowledge of TS biological pathways facilitates the design of mechanism-based inhibitors.
  • Discovery of pathogen-specific TSCP (ThyX) presents new opportunities for selective inhibition.

Conclusions:

  • Advanced techniques like omics are crucial for identifying novel drug targets and mechanisms.
  • TS remains a significant target, with potential for broader therapeutic applications beyond cancer.
  • The identification of TSCP (ThyX) opens new avenues for developing targeted anti-infective agents with unique mechanisms of action.