Efficient drug discovery pipeline and lead compounds for Alzheimer's disease

This technology is a comprehensive compound design and preclinical testing platform that can be used to develop multifunctional drugs for Alzheimer’s disease, and has already led to the development of several promising lead compounds.

Unmet Need: Platform for multi-target drug development and preclinical testing

Many diseases including Alzheimer’s disease are multifaceted and likely require interventions in several cellular processes. However, current drug discovery and testing pipelines focus on single targets and rely on costly and reductionist in vitro assays. Using rodents in pre-clinical tests are costly.

The Technology: Comprehensive platform enabling development of multi-target therapeutic compounds

This customizable platform establishes and screens drug candidates for a multi-target directed ligand Alzheimer’s treatment approach, based on in vitro and in vivo efficacy measures. The platform has led to the identification of several promising and preclinically verified lead compounds, ready for further development as Alzheimer’s therapeutics. Combining organic synthesis with an in vitro pharmacophore iteration model enables cytotoxicity studies, membrane permeability readouts, among other pharmacodynamic outcomes. These methods are complemented by the inclusion of rapid, large-scale preclinical animal testing. A humanized zebrafish model, harboring amyloid and tau toxicity with humanized genetic alterations associated with Alzheimer’s disease can be used in a modular manner to assess the efficacy of lead compounds. Single cell transcriptomics, histopathological assessment, cognitive behavioral tests are used to measure synaptic protection, immunomodulatory activities, vascular integrity and neurogenesis.

This technology has been validated through the discovery of several promising lead candidate compounds for multi-target Alzheimer’s treatment.

Applications:

• Platform for drug discovery and screening
• Development of newly discovered lead compounds for Alzheimer’s treatment
• Platform for drug dosage optimization, increasing efficacy of known drugs
• Research platform for phenotyping preclinical models of disease

Advantages:

• Reduces costs of drug development
• Accelerates in vivo preclinical screening
• Enables testing of large sets of compounds
• Addresses multi-faceted aspects of disease
• Customizable platform
• Can be applied to various therapeutic targets
• Comprehensive preclinical safety and efficacy measures, with biologically relevant testing
• Need-based customization and model development/refinement possible

Lead Inventor:

Caghan Kizil, Ph.D., M.Sc.

Related Publications:

• Turgutalp B, Bhattarai P, Ercentin T, Luise C, Reis R, Gurdal EE, Isaak A, Biriken D, Dinter E, Sipahi H, Schepmann D, Junjer A, Wünsch B, Sippl W, Gulcan HO, Kizil C, Yarim M. “Discovery of potent cholinesterase inhibition-based multi-target-directed lead compounds for synaptoprotection in Alzheimer’s disease.” J Med Chem. 2022 Apr 22; 65(18): 12292-12318.

Tech Ventures Reference:

• IR CU23156

• Licensing Contact: Sara Gusik