Identification of inhibitors of the pro-survival protein Mcl-1
Supervisor: Dr Lesley Howell
The ability to evade cell death is a characteristic of cancer and there are many different cellular mechanisms which cancer cells employ to achieve this. One such example is Mcl-1, a member of a larger family of proteins called the Bcl-2 family. This family of proteins contains around 20 members and is responsible for controlling the programmed cell death pathway. There are both pro- and anti-death proteins which in a healthy cell are carefully balanced. However, in cancer high levels of the anti-death (pro-survival) proteins are often observed and contribute to the development of the tumour. In particular, high levels of Mcl-1 are one of the most commonly observed abnormalities in human cancer, and are associated with the observed resistance to current therapies.[4,5] This PhD seeks to address this problem and identify novel small molecule inhibitors of Mcl-1. It will involve both solution and solid phase organic synthesis as well as the biophysical and biological evaluation of the compounds identified.
Eligibility and applying
Applicants must have an undergraduate degree in chemistry or pharmacy awarded with upper second class honours.
Details of the application process can be found on this webpage.
- Hanahan D, Weinber RA, Cell, 2011, 144, 646
- Juin P, Geneste O et al, Nat. Rev. Cancer, 2013 13, 455
- Beroukhim R, Mermel CH et al, Nature, 2010, 463, 899.
- Wei S-H, Dong K et al, Cancer Chemother. Pharmacol., 2008, 62, 1055
- Wertz IE, Kusam S et al, Nature, 2011, 471, 110