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Design and Synthesis of Mcl-1 Inhibitors

Information

  • Start date: October 2013
  • Programme: PhD
  • Mode of Study: Full Time
  • Studentship Length: 3 years

How to Apply

  • Deadline: 31 July 2013. Applications are processed as soon as they are received, so early application is encouraged. NB applicants who wish to start their studies in October 2013 should submit their application by 31 July 2013 at the very latest. Applications received after this date will be considered for the January 2014 entry point if the project is still available.
  • Apply online

Fees & Funding

Entry Requirements

  • Acceptable First Degree:

    A relevant subject area (Pharmacy, Chemistry)

  • Minimum Entry Standard: The standard minimum entry requirement is 2:1

Project Description

Resistance in the apoptosis pathway often involves a defect preventing the induction of the cell death mechanisms. Approaches that specifically target these mechanisms have received increasing attention over recent years.  The Bcl-2 family of proteins consists of over 20 members and are key regulators of apoptosis. Mcl-1, an anti-apoptotic member of the Bcl-2 family of proteins, is over expressed in a variety of cancers leading to resistance to current therapies. For example the clinical candidates ABT-737 & ABT-263 are potent inhibitors of Bcl-2 & Bcl-XL but do not bind to Mcl-1 deeming them ineffective as single agents. Therefore compounds that specifically target Mcl-1 may overcome this resistance

References

Akgul, C., Cell Mol. Life. Sci., 2009, 66, 1326-1336

Michels, J., Johnson, P. W. M., Packham, G., Int. J. Biochem. Cell Biol., 2005, 37, 267-271

Nguyen, M et al, PNAS, 2007, 104, 19512-19517
 



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