The poster presentations are:
- Using the Novel KINect Platform to Discover Drugs Targeting the Human Protein Kinase Cysteinome; presented by W. Taylor
- Poster 127
Thursday, Sept. 27
- Development of Mitogen-Activated Protein Kinase Activated Protein Kinase-2 (MK2) Inhibitors Designed to Selectively Inhibit the p38/
MK2 Complex; presented by J. Monahan
- Poster 126
Thursday, Sept. 27
The abstracts will be available in the conference program book.
One poster describes Aclaris’ proprietary KINect™ platform for human protein kinase cysteinome drug discovery. Many human diseases, including cancer, diabetes, and chronic inflammation, may involve abnormal cellular function as a result of dysregulated activity of protein kinases. The KINect platform facilitates the development of new drugs targeting protein kinases. Roughly two-thirds of kinases in the human kinome have cysteine residues located near the active site (cysteinome) which can be covalently labeled with inhibitors containing an electrophile.
The KINect platform includes a novel chemical library of several hundred compounds specifically designed to bind reversibly to the target kinase of interest and engage in a covalent manner the non-catalytic cysteine residues near the ATP binding site of more than 300 kinases. The platform also features powerful Schrödinger™ drug modeling software, allowing scientists to optimize target affinity and minimize kinome crossreactivity. The platform enables the assessment of the function of the newly created drug compounds with physiologically relevant custom assays which translate to human diseases.
“The KINect platform is redefining what's possible in the discovery and development of new compounds and new approaches to treating patients with debilitating autoimmune and inflammatory diseases," said
A second poster describes the development of a new drug candidate targeting a key kinase signal transduction pathway: a novel selective inhibitor of the p38/MK2 axis for the treatment of autoimmune disease. The p38 kinase pathway is central to the production and function of key inflammatory cytokines such as TNFα, IL-1, and IL-6. However, drugs directly targeting p38 kinase have not been developed due to safety concerns and transient efficacy observed in clinical trials. Aclaris has taken the novel approach of specifically targeting the proinflammatory p38/MK2 pathway relative to other pathways downstream of p38 involved in maintaining cellular homeostasis or with anti-inflammatory functions. This approach resulted in the discovery of ATI-450, a compound that selectively interacts with the p38/MK2 complex and has demonstrated activity in multiple animal models of chronic inflammatory disease, and is differentiated from global p38 inhibitors in the tachyphylaxis observed in an inflammation mouse model.
Aclaris provides access to the KINect platform to partner pharmaceutical companies and provides drug discovery services through its subsidiary, Confluence Discovery Technologies, a contract research organization. Confluence is an exhibitor and supporter of the Discovery on Target meeting.
Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as "believe", "expect", "may", "plan," "potential," "will," and similar expressions, and are based on Aclaris' current beliefs and expectations. These forward-looking statements include expectations regarding the pre-clinical and clinical development of Aclaris protein kinase inhibitor compounds. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Aclaris' reliance on third parties over which it may not always have full control, and other risks and uncertainties that are described in the Risk Factors section of Aclaris' Annual Report on Form 10-K filed for the year ended
Senior Vice President
Corporate Strategy/Investor Relations
Source: Aclaris Therapeutics, Inc.