The Makoto Platform
Makoto specializes in the identification of the molecular targets and mechanisms of action of small molecules with therapeutic potential. The Makoto approach involves the generation of a Makoto Activity Profile (MAP), target discovery, and target confirmation. To date, the MAP has identified the targets of more than 120 active compounds of potential commercial interest.
Makoto recognizes that each small molecule is unique but that through the integration of multiple approaches, insights can be gained into mechanism of action. Makoto’s experienced scientific team customizes its discovery plans for each project to efficiently maximize the opportunity for success.
Makoto Activity Profile (MAP)
Makoto has developed a comprehensive and integrated suite of cell biological and biochemical assays, termed the Makoto Activity Profile (MAP) that can sensitively detect and rapidly classify the mechanism of action of a biologically active small molecule. Makoto’s approach uses a variety of complementary phenotypic assays that detect immediate effects of a small molecule on cell physiology and function unlike gene-profiling or proteomic approaches that yield information about mRNA or protein abundance. The ability to identify early responses to small molecule perturbation greatly enhances the sensitivity of the approach and is essential in understanding the true mechanism of action of a compound. This platform is used to generate specific compound signatures for compounds having unknown mechanisms of action that are compared to Makoto's growing proprietary database of reference compound signatures, thereby providing insights into mechanisms of action. The MAP reference compound database currently contains the biochemical and cell biological profiles of more than 300 compounds with known mechanisms of action. Makoto's signature generation and comparison strategy enables the Company to rapidly and cost-effectively generate mechanism-of-action hypotheses for active compounds with unknown mechanisms and to rapidly rule-out compounds with mechanisms of limited commercial interest.
Target Discovery and Confirmation
Once the signature generated from MAP suggests a unique and interesting mechanism, Makoto then identifies and confirms targets of small molecules employing a variety of approaches that may include affinity chromatography, SAR studies, assay development, and target modulation.