Drug Discovery
We are dedicated to developing a pipeline of novel product candidates to address the needs of patients with immuno-inflammatory diseases who lack satisfactory treatment options. Our methods include the following:
We are advancing biologics programs focused on well-characterized pathways in immuno-inflammatory diseases. Our approach leverages established biological targets while incorporating novel mechanisms and dual-targeting strategies to potentially enhance therapeutic outcomes.
We are also exploring the kinome, a subset of the human genome that consists of a collection of 518 protein kinases, one of the largest of all human gene families, responsible for signal transduction controlling cellular responses. Our drug discovery efforts are focused on exploring the kinome to unlock new possibilities.
Exploring the kinome to unlock new possibilities
With our sights set on discovery, Aclaris is currently exploring the kinome, a subset of the human genome that consists of a collection of approximately 518 protein kinases, one of the largest of all human gene families, responsible for signal transduction controlling cellular responses.
Classified into eight major groups based on their structural similarity to each other, kinases are key regulators of cell function for many cell processes. By transferring phosphates to other molecules, kinases can induce a cellular response to environmental cues. Dysregulation and/or activating/blocking mutations in kinases can disrupt normal cell signaling and lead to diseases ranging from autoimmune diseases to diabetes and cancer, making them important targets for drug development.
Currently, there are a number of approved kinase inhibitors on the market, such as Xeljanz®* (tofacitinib), Gleevec®* (imatinib mesylate), and Tarceva®* (erlotinib). However, these drugs only target a small fraction of the kinome, with many clinically relevant kinases lacking validated inhibitors.
We’re focused on the design and development of kinase inhibitors that target key enzymes involved in chronic inflammation, autoimmune disease, or the regulation of cancer growth, survival and metastasis.
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KINect® platform: proprietary discoveries through kinome innovation
Our proprietary KINect® platform accelerates the identification of drug candidates through a unique combination of our proprietary chemical library of kinase inhibitors, our expertise in structure-based drug design, and our custom kinase assays.
Central to the KINect® platform is our novel chemical library of several hundred compounds specifically designed to target non-catalytic cysteine residues near the adenosine triphosphate (ATP) binding site of more than 300 kinases.
Using powerful drug modeling software, we are able to elaborate the structure of viable drug-like compounds culled from our library to optimize reversible binding to the target kinase and allow them to selectively form a covalent bond with the cysteine residue near the ATP site on the specific kinase target.
We then assess the function of the newly created drug candidates with physiologically relevant custom assays that effectively translate to human diseases.
The KINect® platform allows us to discover novel drug candidates in a fraction of the time of traditional approaches: 1-2 months to identify and optimize novel lead chemical series that bind to a target of interest versus more than six months to years for traditional approaches that lack a tailored library.
The platform will generate inhibitors with fit-for purpose mechanisms ranging from reversible, to reversible-covalent to irreversible-covalent. These drug candidates have the potential to overcome kinome selectivity and biochemical inefficiency issues faced by other approaches for validated kinase targets.
