Drug Discovery and Development Platform
Symposium: Kinase Drug Discovery – Strategies for Success
A half day dedicated to kinases in drug discovery organized by SciLifeLab DDD in collaboration with AstraZeneca.
Kinases continue to attract much attention in drug discovery. Since the first compounds were launched in 2001 the learning curve of how to tackle different challenges has been steep. At the symposium we hope to give a broad overview where the field stands today and the different approaches one can take in drug discovery when interacting with kinases.
In the first part, Stefan Knapp and Lyn Jones will take us through their many years of experience in the kinase field. Stefan Knapp with a background in protein structure centered research and Lyn Jones with experience from both covalent inhibitors and PROTACs.
Examples of topics in this overview part are:
- How to decide on lead generation strategy and screening cascade?
- Understand your disease and the target (e.g. X-rays, DFG in/out, cysteines, allosteric pockets, full length sequence, phosphorylations, what construct to work with to translate to cell, in vivo…)
- How do you evaluate and prioritize your hits?
- What do you need to think of when working in the non-cancer field?
In the second part, we will dive deeper into the details of data generation and data interpretation to learn and discuss different techniques that can be applied to increase the chance for success. Examples of topics in this more technical part are:
- Choosing the right system: constructs, substrates, ATP concentration (understanding SAR vs understanding the effect in cells)
- How to avoid biochemical assay artifacts and what to monitor in an established assay (an example of a misleading assay, consequences, and how it was troubleshooted)
- Importance of mechanistic studies: activation states, target engagement, in-house and third-party selectivity assays.
- Profiling of kinase inhibitors using CETSA Explore
- Combining targeted CETSA HT assays with functional readouts
- How do we interpret the selectivity data from kinase panels
The meeting will be valuable for researchers in the area of drug discovery like medicinal chemists, structural biologists, pharmacologists, protein scientists, toxicologists etc.
This is a hybrid event. Registration for the conference on site is binding.
Units of the DDD Platform
- ADME of Therapeutics
- Biochemical and Cellular Assay
- Biophysical Screening and Characterization
- Human Antibody Therapeutics
- In Vitro and Systems Pharmacology
- Medicinal Chemistry – Hit2Lead
- Medicinal Chemistry – Lead Identification
- Protein Expression and Characterization
- Target Product Profiling & Drug Safety Assessment
- OligoNova Hub (new unit! Read more here)
What do we offer?
The SciLifeLab Drug Discovery and Development (DDD) platform offers integrated drug discovery efforts to the Swedish academic research community. We offer industry-standard infrastructure, expertise, and strategic support for technology development or to help progress projects towards a preclinical proof-of-concept. We work with small molecules, human antibodies, and new modality therapeutics. There are three ways to interact with us:
|Drug development project||Access to resources/instruments/|
technologies at DDD
|Access to spare resources/|
instruments at DDD
Services are offered in the following areas:
- Up to 80 hour free support to prepare your project as a drug discovery project, including an initial drug target product profile, and a lead generation/antibody selection strategy with progression plans
- In collaboration with Chemical Biology Consortium Sweden, logistic solutions and data management for sharing large numbers of compounds (SciLifeLab compound collection)/antibodies.
- In collaboration with Chemical and Pharmaceutical Toxicology at RISE (Södertälje), projects are evaluated for target safety concerns and approved projects are offered chemical toxicity support (in silico profiling of small molecules), immunotoxicity support (antibodies) and safety support in the design of in vivo studies.
- Protein production for assay development
- Identification of binders from our IP free phage display library of human antibodies
- Biochemical and cellular screening, both at single concentration in large compound libraries and to generate dose-response data for iterative chemistry
- Medicinal synthetic and computational chemistry
- Analysis of drug metabolism and pharmacokinetics data for compounds and antibodies
- Advanced analysis of in vitro pharmacology and systems pharmacology of compounds and antibodies
- Biophysical identification of binding partners (small molecules or proteins), screening of chemical libraries and characterization of interactions between hits/leads and their targets, using a range of time-resolved and structure-based biophysical methods
Importantly, the researcher/customer retains all rights and ownership during this process.
For the latest updates, please follow us on LinkedIn.
Achievements and Testimonials
“We couldn’t have done this project without SciLifeLab. To begin with, we didn’t even know which things we didn’t know, so to speak. Nor did we have the funds to be able to do it ourselves. The vast competence of the DDD platform scientists has been invaluable to us.”
Olle Hernell (Umeå University)
“To have access to the expertise and techniques provided by the DDD was critical for us in order to be able to advance our research.”
Tina Sarén (Uppsala University)
A paper titled “An Adaptable Antibody-Based Platform for Flexible Synthetic Peptide Delivery Built on Agonistic CD40 Antibodies” was recently published in Advanced Therapeutics, with many contributors from the DDD Platform. This work was the result of a successful project owned by Sara Mangsbo and her colleagues, which made an exit in 2021.
Since 2020, the DDDP has had high priority on covid-19 through the Nevermore Covid project, which has resulted in promising inhibitors of the Mpro protease of SARS-CoV-2, just published in JACS by Jens Carlsson, Helena Danielsson and others.
“This shows how academic researchers can in fact get results in highly competitive fields such as covid-19 research by working in an open and collaborative environment and by accessing the national infrastructures that DDDP and SciLifeLab provide,” says Kristian Sandberg, platform director for the DDDP. He also adds that other promising molecules have been identified in DNA-encoded library screens performed at the DDDP.
Per Arvidsson, platform director for DDDP, adds: “At the outset of this project, few believed that drugs for covid-19 would be needed given the pace of vaccine development; even more were skeptical that academic efforts could make a meaningful impact in this highly competitive space. Less than two years later, we see a huge global demand for antivirals, and everyone now realizes the importance of preparing for future pandemics by having drug candidates lined up for development. Most impressively, this project demonstrates the power of combining cutting-edge drug discovery technologies, such as virtual screening and DNA encoded chemical screening, with the capabilities available at both national and international infrastructures like SciLifeLab, Max IV Laboratory, and the Diamond Light source, in an international collaboration under a professional project leadership. The team has really done a remarkable job in getting this far in such a short time!”
Watch a video from 2020 by Upptalk Weekly where Jens Carlsson (Uppsala University) talks about this project around SARS CoV-2 main protease drug discovery, and how molecular dynamics simulations can accelerate drug discovery. The video is in Swedish.
The SciLifeLab Symposium: “Accelerating the process from basic drug discovery to clinical trial for Covid-19” from Dec 1, 2020, is available on YouTube.
Recent DDD-exit: Promising antibody candidate in the fight against cancer
A new promising cancer treatment, aiming to inhibit tumor growth by attacking the signaling pathway of transforming growth factor beta (TGFbeta) has just left the SciLifeLab Drug Discovery and Development (DDD) platform. Umeå University based researcher Maréne Landström and her team are behind the project that is aiming for clinical trials in the near future. Read the full article here.
Recent developments at the DDDP
With its mission to support researchers in developing prototypes for new drugs, the DDD platform is focused on providing state-of-the-art drug discovery technologies to scientists across the country. During the last couple of years, the platform has developed DNA-coded chemical libraries that make it easier to find relevant starting points for small molecule drug discovery. In 2020, the platform launched its third library, containing over one million unique DNA-coded drug-like substances. Currently used for COVID-19 projects, the library will be made available for academic researchers nationwide in 2021.
The platform also recently established a new methodology for developing PROTACs
® (Proteolysis targeting chimera), a new kind of drug which breaks down target proteins instead of inhibiting their functions. In 2020, the platform’s researchers – in close collaboration with scientists at Karolinska Institutet, Uppsala University and Recipharm AB – showed the first functional degrader to be produced in Swedish academia. Now, the aim is to make this technology available to users in early 2022.
In 2020, the activities at the platform were in many ways affected by the corona pandemic, but despite restrictions, the platform managed to carry out most of its operations as planned. During the year, it added three new academic projects to its portfolio, and carried out two successful exits; one of which, a project on developing a new kind of cell therapy (CAR-T) for glioblastoma, was advanced into a private company that will continue its development.
The platform also launched two research projects on COVID-19 – one aiming to identify inhibitors of a viral protease essential to the growth of the virus, and one where antibodies with high-binding strength to the virus surface protein have been identified.
The DDD platform has until recently focused on small molecules and protein drugs; a recent addition is oligonucleotides. Oligonucleotide drugs have a potentially faster development compared to other drug types. The OligoNova Hub is based in Gothenburg and will become part of SciLifeLab’s DDD platform.
”This endeavour enables the DDD platform to take on new kinds of projects for diseases with unmet medical needs, and focus on different therapies. It also creates several potential synergies, for instance, a possibility to combine DDD’s unique antibody expertise with oligonucleotide drugs to facilitate delivery to the correct cell type”, says Kristian Sandberg, Co-Director of the platform.
“The OligoNova Hub will establish a vibrant center based on scientific excellence for these new medicines, creating a unique opportunity for SciLifeLab to work on new drugs together with the life science community in Sweden. We look forward to working with the Wallenberg Centre for Molecular and Translational Medicine, to make these technologies available to researchers across the country”, he continues.
We are currently running 19 drug discovery projects at the DDD platform: antibody, small molecule, and technology development projects. The DDD Platform strives to stay up to date with current drug discovery techniques used in the pharmaceutical industry.
Small molecule projects
Recent project exits
|Year||Principal Investigator||Affiliation||Therapeutic area||Project Type|
|2022||Marika Nestor||Uppsala University||Oncology||Antibody|
|2021||Thomas Helleday||Karolinska Institute||Oncology||Small Molecule|
|2021||Maréne Landström||Umeå University||Oncology||Antibody|
|2021||Sara Mangsbo||Uppsala University||Oncology||New Modalities|
|2020||Mattias Hallberg||Uppsala University||Neuroscience||Small Molecule|
|2020||Magnus Essand||Uppsala University||Oncology||New Modalities|
|2019||Susanne Lindqvist||Umeå University||Autoimmune Diseases||Antibody|
|2019||Sonia Lain||Karolinska Institute||Oncology||Small Molecule|
|2018||Margit Mahlapuu||Gothenburg University||Metabolic Disorders||Small Molecule|
|2018||Per Almqvist||Karolinska Institute||Neuroscience||New Modalities|
|2017||Maria Eriksdotter||Karolinska Institute||Neuroscience||Small Molecule|
|2016||Mårten Fryknäs||Uppsala University||Oncology||Small Molecule|
|2016||Johan Flygare||Linköping University||Blood Disorders||Small Molecule|
|2016||Thomas Helleday||Karolinska Institute||Oncology||Small Molecule|
Recent project exit
What a year 2021 has been for our platform! We have celebrated the exits of three very successful projects, the latest of which is Thomas Helleday’s project on MTHFD2 inhibitors. The candidate drug will be further developed in the recently started company One-carbon Therapeutics AB. Read the article here.
Activation of potassium channels
“SciLifeLab Drug Discovery & Development project owner and SciLifeLab board member Professor Fredrik Elinder was interviewed in the ionchannellibrary. He outlines the challenge of undertaking and funding drug discovery efforts in academia, the need for high-throughput ion channel measurements, and ultramarathons – all in one place.
Interested in DDDPs past new articles and achievements? Below are links to older news articles involving the work that is done at our unit.
- Susanne Lindquist’s project (exited DDDP 2019) and further developments of this drug candidate by Lipum AB
- CAR-T project by the Magnus Essand lab (exit 2020) and its further development by Elicera Therapeutics
- Collaboration with Medivir AB in the Nevermore Covid project in 2020
- Sara Mangsbo’s project exit (2021) and its further development by Strike Pharma