Metabolites were historically thought to be little more than sources of energy and molecular building blocks in cells, but recent research has started to unveil the regulatory potential of metabolites. Our approach revolutionizes the discovery of new allosteric protein-metabolite interactions to develop novel small molecule therapeutics.
Identification and structural characterization of the binding sites on proteins that are engaged by metabolites can deepen our understanding of how a variety of cellular and molecular processes are governed. Atavistik has built a robust mass spectrometry-based screening platform using cutting edge informatics to discover and characterize novel regulatory sites. We are combining this knowledge with the state-of-the-art artificial intelligence-machine learning integrated structure-based drug design tools to discover new therapeutics.
Atavistik Metabolite Protein Screening (AMPS)
It has been historically challenging to systematically assess the vast number of potential metabolite-protein interactions and allosteric regulators of drug targets. Atavistik Bio has overcome this challenge using the Atavistik Metabolite Protein Screening (AMPS) platform, which is an enhanced and industrialized version of a technology developed at the University of Utah.
By leveraging our optimized AMPS platform and computational approaches, we aim to evaluate metabolite-protein interactions by screening proteins with our proprietary metabolite library to determine where binding sites with biological relevance might exist and build an extensive protein-metabolite database map (the “Interactome”) to reveal unique insights into the crosstalk between metabolite-protein pathways that were previously thought to be unrelated. Utilizing advanced informatics tools, our deep expertise in chemistry and computationally rich structure-based drug design, we will be able to identify and understand the role of these interactions across important biological and disease-relevant pathways to drive the discovery of novel therapeutics.
Identifying metabolite-protein interactions in a robust manner holds vast therapeutic potential. Endogenous metabolites bind proteins with functional implications in pathways related to every known cellular process. Atavistik Bio currently has two primary areas of therapeutic focus, while considering collaborations with scientists from a variety of other areas of research.
Inborn errors of metabolism are a family of devastating genetic diseases that impact patients of all ages. Many of these diseases are monogenic which lead to impaired function of a single metabolic enzyme. Due to intricate and widespread crosstalk between metabolic pathways, dysfunction in one metabolic pathway can have devastating effects on multiple cellular processes across multiple organs. We seek to understand this crosstalk by mapping the landscape of protein-metabolite interactions across multiple metabolic pathways dysregulated in disease. Characterization of how metabolites regulate various metabolic pathways through identification of the relevant metabolite binding sites on enzymes mutated in disease can lead to the development of a therapeutic compound to correct its function.
Cancer is the second leading cause of death globally. Cancer arises due to genetic alterations in proteins required for signaling, growth and metastasis. Genetic alterations of transcription factors and cellular signaling proteins have been shown to result in the rewiring of the cellular metabolome to support tumorigenesis. Identification of the interaction between metabolites and genetically validated cancer genes provides a starting point for the rationale design of therapeutics that modulate their function and ablate tumor growth.
Atavistik Bio's screening platforms have broad applicability as we believe a wide array of cellular processes have evolved to sense the nutrient environment. While our current two areas of focus involve well validated disease targets with a high probability of translational success, we plan to expand our efforts into proteins and other macromolecules that have been validated as driving a wide array of disease pathology from CNS-related disorders to disorders of the immune system to cardiovascular disease.