CYPNASH SIGNED
Validation of a novel class of cyclophilin inhibitors for the treatment of non-alcoholic steatohepatitis
Total Cost €
0EC-Contrib. €
0Partnership
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0CYPNASH project word cloud
Explore the words cloud of the CYPNASH project. It provides you a very rough idea of what is the project "CYPNASH" about.
Project "CYPNASH" data sheet
The following table provides information about the project.
| Coordinator |
THE UNIVERSITY OF EDINBURGH
Organization address contact info |
| Coordinator Country | United Kingdom [UK] |
| Total cost | 0 € |
| EC max contribution | 150˙000 € (0%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2019-PoC |
| Funding Scheme | ERC-POC-LS |
| Starting year | 2019 |
| Duration (year-month-day) | from 2019-10-01 to 2021-03-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | THE UNIVERSITY OF EDINBURGH | UK (EDINBURGH) | coordinator | 150˙000.00 |
Map
Project objective
Non-alcoholic steatohepatitis (NASH) is an increasingly prevalent chronic liver disease (3-4% of the US population) for which there is currently no approved drug therapy. In the absence of innovative treatments healthcare costs associated with this disease are set to triple over the next decade. To address this unmet medical need, the pharmaceutical industry is currently pursuing a range of liver fibrosis drug discovery programs based on different mode of actions. A compelling mechanism for treating liver damage is pharmacological modulation of the mitochondrial permeability transition pore in liver cells via inhibition of the protein cyclophilin D. However existing cyclophilin inhibitors based on peptidic macrocyclic scaffolds are challenging to optimize into sub-type selective orally bioavailable agents suitable for clinical trials of liver fibrosis.
As part of basic research activities undertaken during ERC StG EBDD to validate a computational-biophysical drug discovery platform, we have discovered a structurally novel family of small molecules that inhibit cyclophilins by targeting a previously unexplored binding pocket. The objective of this POC is to identify a lead compound in this family with potential for development towards a NASH clinical candidate. Such a candidate will form the basis of follow-on lead optimisation programs pursued via partnering or out-licensing with a pharmaceutical partner. The activities of this POC will focus on assembling a data package of in vitro DMPK, in vivo PK, in vitro sub-type selectivity and in vitro and in vivo efficacy measurements in relevant cellular and animal models of liver fibrosis. This POC has been designed in consultation with a major pharmaceutical company and assembles a team of physical and biological scientists and business development executives to maximize the likelihood of delivering a valuable preclinical NASH asset.
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