RATIONAL DESIGN OF KINASE INHIBITORS TO TREAT PANCREATIC CANCER ABOUT THE PROJECT

Pancreatic cancer, in particular, pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal human cancers with an overall median survival time of 6-9 months. Treatment regimens for PDAC rely of surgical intervention which has a 90% re-emergence rate, paired with poor prognosis and limited 5-year survival rates (<10%). Pharmacological treatments fair no better, with standard of care in PDAC having marginally better outcomes. Therefore, it is imperative that new biological pathways are interrogated for their role in PDAC, coupled with the development of small molecules designed to selectively interfere with this pathway.

Ongoing work within the McLaughlin group has identified a potential tyrosine kinase target that has been shown to have a key role in PDAC tumorigenesis and is overexpressed in numerous patient biopsies. Several studies have shown that through inhibiting this kinase’s signalling pathway, PDAC growth and self-renewal was significantly reduced, thus presenting clear validation for drug development, however more work is required to validate and corroborate these findings.

This project will therefore focus on the development of small molecule inhibitors of this tyrosine kinase, which will enable the project team to interrogate its importance in PDAC, with the aim to deliver a promising small molecule lead compound. This objective will be achieved via a cutting-edge computational workflow coupled with traditional wet chemistry. The project is a collaboration between medicinal chemistry (Dr Mark McLaughlin) and molecular modelling (Dr Irina Tikhonova), and the student will have ample training in each aspect of the project.

Applicants should hold, or expect to receive, a 1st or 2:1 Honours degree in chemistry or a related subject. A master’s level qualification would also be advantageous. Applications are particularly welcome from students with experience in organic or medicinal chemistry however this is not essential.

Informal enquiries are encouraged and should be directed to Dr Mark McLaughlin ([Email Address Removed])