EUREKA-Eurostars; CystArrest (grant number 01QE1857)

Duration: 2018-2022 | Grants awarded: € 1,646,077, of which Endotherm received: € 298,000

Development of a drug against Polycystic Kidney Disease (PKD)
Subproject: Development and optimization of a new drug by chemical structural variations.

Genetic PKD results in the formation of fluid-filled cysts in the kidney. Long-term consequences are renal insufficiency and eventually chronic kidney failure. Ultimately, this can only be countered by lifelong dialysis or organ transplantation. Current therapies are purely symptomatic and do not address the causes of disease.

Preliminary work by a project partner (Perha Pharmaceuticals, Roscoff, France) has shown that certain kinase inhibitors (e.g., roscovitine) previously developed in cancer research can prevent the formation of cysts in the kidney. These compounds could also be suitable therapeutics against PKD after appropriate further development.

Already discovered compounds (hits) can be structurally improved by Endotherm Life Science Molecules with regard to their efficacy and bioavailability by chemical structural modifications (hit-to-lead studies) until a lead structure is found that has the desired properties in the project partners' in vitro assays and 3D imaging models.

Already discovered compounds (hits) can be structurally improved by Endotherm Life Science Molecules with regard to their efficacy and bioavailability by chemical structural modifications (hit-to-lead studies) until a lead structure is found that has the desired properties in the project partners' in vitro assays and 3D imaging models.

In the second step, further optimization of the lead structure will be performed and a drug candidate is developed that is capable of curing disease in an animal model with low toxicity and an acceptable side effect profile. The bioisosteric method, which is well established in medicinal chemistry, is used for this purpose. In this approach, efficacy and bioavailability are optimized by chemically varying individual elements of the parent molecule through multiple rounds of structural variation and testing until an ideal drug candidate is found for clinical studies.