Ambagon Therapeutics

Ambagon observes #Juneteenth, commemorating the emancipation of enslaved African Americans in the United States. We are committed to creating a more equitable future for all, starting with an inclusive work environment and a diverse team. Learn more about Ambagon's team here: https://lnkd.in/dWQGPAMx

14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to their Small-molecule Stabilization We’re excited to share our latest publication on molecular glues of 14-3-3 proteins by our scientific co-founders, Michelle Arkin, Luc Brunsveld, and Christian Ottmann, along with Bente Somsen and Peter Cossar. This review highlights the potential of targeting 14-3-3 protein complexes with small molecule modulators, showcasing their promise as therapeutic agents and tools for deeper molecular insights. Link to article: https://lnkd.in/dWQvgf_Q

At Ambagon, we stand proudly with the LGBTQ community in celebration of diversity, equality, and love. Throughout this month, and always, we're committed to fostering an inclusive workplace where everyone feels valued and respected for who they are. Join us in celebrating love, equality, and diversity this Pride Month. #PrideMonth

14-3-3 modulates α‑Synuclein multimerization and amyloid formation   Our scientific co-founders have published a study demonstrating that the hub protein 14-3-3 modulates the multimerization of α-synuclein (α-Syn), the aggregation of which plays a key role in the etiology of Parkinson’s Disease. The paper, published in ACS Chemical Neuroscience, characterizes how 14-3-3τ controls this multimerization and the formation of amyloid, allowing α-Syn to remain soluble and functional.   This study provides a rationale for the development of molecular glues to enhance the binding between α-Syn and 14-3-3 for blocking pathologic α-Syn aggregation. The authors are Ambagon scientific co-founders Christian Ottmann and Luc Brunsveld, together with Maxime van den Oetelaar, Eindhoven University of Technology, and collaborators at the University of Twente Gobert Heesink, Slav Semerdzhiev, Christian Blum, and Mireille Claessens. Read more here: https://lnkd.in/gPY23xgQ   At Ambagon, we develop 14-3-3 molecular glues to address targets that have been impossible or challenging to drug with small molecules – such as α-Syn – or to modulate target biology in ways that are unavailable with other approaches.   To learn more about how we expand the druggable proteome, visit https://www.ambagontx.com. 

World Parkinson’s Day, observed on April 11th, raises awareness about the challenges faced by individuals with Parkinson’s disease (PD).   At Ambagon, we aim to make a meaningful difference in the lives of those impacted by Parkinson’s and advance towards a future with better treatment options and ultimately, a cure. To this end, we are developing a novel approach to inhibit one of the most frequently overactivated proteins in familial and sporadic PD: We have obtained initial proof of concept for inhibition of LRRK2 via stabilization to 14-3-3 with a molecular glue. This represents a differentiated approach that may enable us to overcome limitations of existing therapies targeting this protein.   https://lnkd.in/eNVsNuR3

In a collaboration of the academic group of our co-founders Luc Brunsveld and Christian Ottmann with the University of Duisburg-Essen (Germany) and the Icahn School of Medicine at Mount Sinai (New York), molecular glues of the 14-3-3/ChREBP complex have been identified that prevent the death of human beta cells under high glucose/high lipid conditions (glucolipotoxicity). In the paper, recently deposited at BioRxiv (Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity | bioRxiv), the authors describe the optimization of compounds that stabilize the cytoplasmic interaction of 14-3-3 with the transcription factor ChREBP, prevent its nuclear import and consequently inhibit its transcriptional activity. This protects human beta cells from glucolipotoxity-induced cell death and – importantly – maintains their insulin production. These 14-3-3/ChREBP molecular glues could be valuable starting points for the development of beta cell protective agents for therapeutic intervention in diabetes. https://lnkd.in/gQMixSim

At Ambagon, our journey is driven by our core values, one of which is passion. Passion fuels our creativity, encourages collaboration, and inspires us to make a meaningful impact in what we do.   We are passionate about developing novel approaches to tackle previously undruggable targets with molecular glues that stabilize these targets to the regulatory hub protein 14-3-3 for therapeutic benefit.    To learn more about our science: https://lnkd.in/eNVsNuR3

Our scientific co-founders Christian Ottmann and Luc Brunsveld, TU/e colleagues Emira Visser, Marloes Pennings, Peter Cossar, and academic collaborators at Mt. Sinai, Liora Katz, PhD, Donald Scott, Isabelle Tse, and the University of Duisburg-Essen, Markus Kaiser, Kathrin Plitzko, recently published on the potential application of a 14-3-3 molecular glue approach for diabetes: Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity. This differentiated approach may provide a novel therapeutic strategy to address not only diabetes, but also other metabolic diseases such as nonalcoholic steatohepatitis (NASH) and fatty liver disease (NAFLD). View the report here: https://lnkd.in/gC_Zu8tW

Ambagon CSO, Nancy Pryer, Ph.D., and VP of Chemistry, Steven Richards, Ph.D., will talk about the early days of Ambagon during “The Science and Stories of Promising Biotech Startups" on February 22nd, a free online symposium hosted by the Pharmaceutical and Bioscience Society (PBSS).    Register here: https://lnkd.in/eH6P6z8K

On International Day of Women and Girls in Science, February 11th, we proudly celebrate the achievements and contributions of women in science. At Ambagon, we are privileged to have a team of brilliant female scientists who continually drive innovation and excellence. We honor their dedication, passion, and the impact they make in shaping the future of science. Let's continue to champion diversity in STEM fields, fostering an environment where every voice is heard and celebrated!   Meet our team members: https://lnkd.in/dWQGPAMx