Pioneering Inverse Drug Discovery for Kidney Disease
Despite the high burden of kidney and cardiorenal-metabolic diseases, progress in drug discovery for these conditions has been slow. This is largely due to the complexity of the kidney proteome and a lack of well-defined, druggable targets. The KIDnEx2 project aims to change that. Through an innovative inverse drug discovery (IDD) approach, the project will map and explore the ligandable proteome of the kidney to identify novel therapeutic targets and support the development of new treatments.
From Fragments to Function: The Scientific Aim
At the heart of the project is a library of novel electrophilic scout fragments, designed to probe the proteome of kidney cells in both human and animal models. This unbiased approach allows the team to discover and prioritize protein targets that are often overlooked—especially those involved in podocyte function and metabolic regulation. These insights will provide a foundation for new drug discovery efforts in areas of high unmet medical need.
“KIDnEx2 harnesses ODIN’s open, collaborative environment to drive our inverse drug discovery approach for kidney and cardiorenalmetabolic diseases,” says Markus Rinschen, Head of the KIDnEx2 project. “With ODIN’s unique ecosystem of expertise and resources, we can efficiently uncover and validate novel therapeutic targets, propelling transformative drug discovery forward.”
Thomas Poulsen, a chemist on the KIDnEx2 project, adds:“We’ll be exploring the use of covalent scout fragments to map new targets in the kidney proteome. It’s a unique opportunity to showcase new classes of reactive groups that could have much broader applications, also beyond the KDInEx2 project.”
What is Inverse Drug Discovery (IDD)?
In traditional drug discovery, researchers search through thousands of compounds to find one that binds to a known target. In IDD, the process is reversed: researchers start with carefully designed small molecules (fragments) and use them to uncover new targets.
The KIDnEx2 team uses covalent scout fragments—small molecules that can form stable, direct bonds with proteins. This allows them to systematically map which proteins in kidney cells are druggable.
Uniting Academia and Industry to Drive Innovation
KIDnEx2 is a true academia-industry collaboration. The project includes university researchers, biotech and pharma partners, and contributors to open science.
Gubra contributes advanced rodent models of diabetic kidney disease. “We're excited to join the KIDnEx2 project to explore new mechanisms of action and support innovation in drug discovery within kidney disease,” says Michael Christensen, Principal Scientist at Gubra. “By sharing samples from our models, we hope to help drive progress in cardiorenal metabolic research.”
Data sharing and openness are central to the project. All datasets, protocols, and the scout fragment library will be made available to the wider research community. grit42 supports the project’s data management using their open-source platform ‘grit’.
“Our participation in KIDnEx2 is a perfect opportunity for us to validate that we have succeeded in creating a platform that allows researchers to easily manage and share data during and after projects,” says Claus Stie Kallesøe, CEO of grit42.
Together, the KIDnEx2 team aims to build a scalable research pipeline that can benefit not only kidney research, but other disease areas in need of fresh therapeutic strategies.
Meet the team and the expertise driving the KIDneX2 project
The KIDnEx2 team is truly interdisciplinary and counts three main academics and three companies:
- Markus Rinschen (Aarhus University)
Leads the overall project and manages coordination across partners. Markus is a renal biologist and will be responsible for mass spectrometry data generation, biochemical and preclinical validation. He will also provide both animal models and native human tissue. - Thomas Poulsen (Aarhus University)
A chemist with expertise in chemical biology, Thomas will lead the design and synthesis of the scout fragment library and all related chemistry work. He is responsible for coordinating the experimental ABPP (activity-based protein profiling) workflow in close collaboration with Markus Rinschen. - Amelie Stein (University of Copenhagen)
Amelie is a computtational structural biology and will lead large-scale in silico analysis of target sites using cutting-edge modeling and bioinformatics approaches. She will prioritize the most promising ligandable sites for follow-up and validation. - AstraZeneca
The team from AstraZeneca consists of Asha Seth, who is a cardiorenal scientist, and Karolina Nilsson, a medicinal chemist. Asha is responsible for providing animal models and strategic oversight, where as Karolina will advise on scout library construction, ABPP workflows, and pocket detection analyses. Together, they contribute to target selection, validation, and sourcing additional human tissue if needed. - Gubra
The Gubra team consists of Michael Christensen, Frederikke Emilie Sembach, and Maria Ougaard. As preclinical model experts, they will provide snap-frozen kidney samples from advanced animal models and advise on model translatability and therapeutic relevance.. - grit42
The team from grit42 headed by Claus Stie Kallesøe provides the open-source platform ‘grit’ for data and project management, supporting transparent sharing and tracking of all project outputs, including scout fragment synthesis.epresenting the project’s industry partner, Anja contributes crucial know-how in translational drug discovery, metabolic disease models, and high-throughput screening. She plays a central role in aligning the project with real-world drug development needs.