Small molecules and their roles in effective pre-clinical target validation

Michael Clegg, Nicholas C. O. Tomkinson, Rab K. Prinjah, Philip G. Humphreys

Research output: Contribution to journal › Article

Abstract

As demonstrated in multiple historical analyses, there are two main causes of clinical attrition; firstly drugs are not efficacious, and secondly they cause unacceptable toxicity, both of which can be the result of poor pre-clinical target validation. Target validation, one of the early stages of a drug discovery program, is the process of (in) validating a drug target to ensure it is significant to the intended disease, and unlikely to drive undesired toxicity. Target validation is vital in preventing late stage failures in the clinic and, if done effectively, can save pharmaceutical companies a great deal of time and money. As such, target validation is treated extremely seriously, as demonstrated by the formation of public - private partnerships, such as Open Targets, aimed to provide evidence of biological validity and the possible likelihood of pharmacological intervention. Central to the variety of molecular tools available for use in target validation are high quality small molecules called chemical probes.
LanguageEnglish
Number of pages5
JournalFuture Medicinal Chemistry
Publication statusAccepted/In press - 19 May 2017

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Public-Private Sector Partnerships
Pharmaceutical Preparations
Drug Discovery
Pharmacology

Keywords

  • chemical probe
  • target validation
  • bromodomain
  • BET

Cite this

Clegg, Michael ; Tomkinson, Nicholas C. O. ; Prinjah, Rab K. ; Humphreys, Philip G. / Small molecules and their roles in effective pre-clinical target validation. In: Future Medicinal Chemistry. 2017.
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Clegg, M, Tomkinson, NCO, Prinjah, RK & Humphreys, PG 2017, 'Small molecules and their roles in effective pre-clinical target validation' Future Medicinal Chemistry.

Small molecules and their roles in effective pre-clinical target validation. / Clegg, Michael; Tomkinson, Nicholas C. O.; Prinjah, Rab K.; Humphreys, Philip G.

In: Future Medicinal Chemistry, 19.05.2017.

Research output: Contribution to journal › Article

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AU - Prinjah, Rab K.

AU - Humphreys, Philip G.

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AB - As demonstrated in multiple historical analyses, there are two main causes of clinical attrition; firstly drugs are not efficacious, and secondly they cause unacceptable toxicity, both of which can be the result of poor pre-clinical target validation. Target validation, one of the early stages of a drug discovery program, is the process of (in) validating a drug target to ensure it is significant to the intended disease, and unlikely to drive undesired toxicity. Target validation is vital in preventing late stage failures in the clinic and, if done effectively, can save pharmaceutical companies a great deal of time and money. As such, target validation is treated extremely seriously, as demonstrated by the formation of public - private partnerships, such as Open Targets, aimed to provide evidence of biological validity and the possible likelihood of pharmacological intervention. Central to the variety of molecular tools available for use in target validation are high quality small molecules called chemical probes.

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Clegg M, Tomkinson NCO, Prinjah RK, Humphreys PG. Small molecules and their roles in effective pre-clinical target validation. Future Medicinal Chemistry. 2017 May 19.

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