Development of Small Molecule EPAC1 Activity Modulators
Lead Research Organisation:
Heriot-Watt University
Department Name: Sch of Engineering and Physical Science
Abstract
This is a PhD Research project in chemistry. This project is part of an ongoing collaborative research effort across several groups at Heriot-Watt and other institutions. The project will involve the design and synthesis of small molecule agonists and antagonists for the cellular signaling enzyme EPAC1. Design will be carried out by generating computational models of energetically favorable docking modes of existing ligands into EPAC1 homology model crystal structures before examination of these models and identification of new target analogue structures. Synthesis will then be undertaken using a wide variety of organic synthetic chemistry techniques. Samples of new compounds will then be passed on to collaborators for evaluation of biological activity.
Organisations
Publications
Luchowska-Stanska U
(2019)
Selective small-molecule EPAC activators.
in Biochemical Society transactions
Morgan D
(2020)
Recent Developments in C-H Functionalisation of Benzofurans and Benzothiophenes
in European Journal of Organic Chemistry
Wang P
(2020)
Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators.
in Journal of medicinal chemistry
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509474/1 | 01/10/2016 | 30/09/2021 | |||
| 2123467 | Studentship | EP/N509474/1 | 01/10/2018 | 31/03/2022 | David Morgan |
| EP/R513040/1 | 01/10/2018 | 30/09/2023 | |||
| 2123467 | Studentship | EP/R513040/1 | 01/10/2018 | 31/03/2022 | David Morgan |
| Description | As a result of the work undertaken through this award, we have successfully synthesised a range of EPAC analogues, conducting preliminary structure activity relationship studies on two structurally distinct series (I942, and SY000). This work led to the publication of manuscripts in high impact journals (J. Med. Chem., Cells). We have developed and optimised a new synthetic route for the synthesis of novel EPAC activators first identified in collaboration with Dr. Steven Yarwood. Additionally, this award has led to my personal development and provided myself with the opportunity to learn a range of new skills as well as develop existing ones. |
| Exploitation Route | The outcomes of this funding will be taken forward by the PI, through future PhD Students/Postdoctoral researchers joining the group, or through collaborations with other research groups. This work is relevant to the pharmaceutical industry, and therefore non-academic collaborations could be developed. |
| Sectors | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |