HTS campaigns for kinase inhibitors often result in numerous hits. The selection of the most promising hits and the identification of potential lead series can be challenging regarding kinome selectivity and also in terms of unfavorable physicochemical parameters.In a HTS campaign for Rho kinase inhibitors more than 3000 hits were obtained. Tools and criteria used to identify and prioritize chemical matter will be discussed including a heat-map tool for visualization of kinase selectivity. Our efforts to optimize a promising single hit using parallel synthesis resulted in tool compounds suitable for proof of concept studies. Examples include enhancement of neurite outgrowth on inhibitory substrates in vitro and regeneration of axons after crushing the optic nerve in vivo.

Identification of selective Rho kinase inhibitors as suitable tool compounds for proof of concept studies

243rd National Meeting (2012)

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