Allo-Glue™ Platform

A breakthrough in genome-scale drug discovery.
Exploring new dimensions in drug discovery by exploiting the intrinsically flexible and modular nature of proteins.

Our chemical biology platform comprises proprietary technology innovations that uniquely enable high throughput drug ligand screening and mapping of small molecule drug-protein interactions directly in living cells, and at an unprecedented scale and level of complexity. Mapping of fingerprints of molecular drug interactions across up to ~20,000 gene products (the human genome equivalent) provides unique insights into therapeutic opportunities and rational drug design optimization strategies.

Our discovery capabilities extend to interrogation of drug modalities that act in an allosteric manner and elicit therapeutic effects by modulating interactions of a small molecule receptor protein with other proteins. These drug modalities, which we call Allo-Glue™ small molecules, act as molecular glues to induce formation of protein complexes that can result in target modulation, including inhibition and degradation, of disease-relevant proteins.

Our genome-scale data acquisition approach provides a unique foundation for pioneering new numerical methods and machine learning-based approaches to chemical innovation and rational design of small molecules, including Allo-Glue™ molecules.

Distal mechanism of action

Allo-Glue™ small molecule can bind to a specific protein and promote target recruitment distal to its binding site in an allosteric manner

Artboard 1Protein + Allo-GlueTargetProtein + Allo-Glue+BINDINGPROTEIN COMPLEXAllo-Glue+Protein

Proximal mechanism of action

Allo-Glue™ molecule complex may also bind to a specific protein and promote target recruitment proximal to its binding site (and directly participate in interaction)

Artboard 1 copyProtein + Allo-GlueBINDINGPROTEIN COMPLEXAllo-GlueProtein+TargetProtein + Allo-Glue+

Possible outcomes on targets

Allo-Glue™ molecule-induced interaction can lead to several possible biological effects on target proteins

Artboard 1 copy 2TargetdegradationTargetinhibitionTargetfunctionchange

Reprogramming protein targets

Allo-Glue™ molecules are a unique class of allosterically acting small molecules that enable access to targets previously thought unapproachable. They act to alter form and function of intracellular proteins, thereby reprogramming their patterns of interaction with other proteins. This may occur distal or proximal to the Allo-Glue™ molecule binding site and may have various effects on disease targets, including their degradation by a cell’s natural protein disposal machinery.

Screening platform

The Orionis platform enables large scale interrogation of small molecule targets over a large dynamic range of interaction intensities across up to ~20,000 human proteins

Artboard 1 copy 301234LogIntensityThousands of Allo-Glues~20.000 targets

Molecular interaction fingerprints

Genome-scale fingerprints provide a unique perspective of drug-target interactions and basis for a new class of numerical methods and chemistry optimization

Artboard 1 copy 4Thousands of Allo-Glues~20.000 targetsOrionis NumericalMethod for Rational Glue Design