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Functional annotation of proteomes remains challenging as proteins do not have rigid molecular structure. Rather, alternative conformations are in constant transition - among themselves and through interactions with other cellular constituents, thereby imparting functional heterogeneity. Understanding the motion and plasticity of active sites would have important implications on the design of enzyme targeted drugs, as it is now generally accepted that drug binding induces large conformational changes.  

Observing this phenomena directly is exceedingly difficult, but by inference - signature functional profiles open up possibilities to catalog and compare observable differences in kinetic response to various in vitro stimuli of the active site. These variants potentially span the continuum of kinetic sub-states acquired by natural transient features and regulatory factors, post-translational modifications, family and mutation amino-acid sequence, or splice variants. Other drug discovery platforms consider either: structural binding analysis by crystallography, the relative expression and PTMs of protein families, and most commonly - selectivity screening of homogeneous panels of recombinant enzymes. However, ProFACT's Conformerics platform proposes to directly determine the kinetic contributions of enzyme variants, and screen compounds against a pooled collection of the most disease-specfic variants.

Conformerics is the trademark term describing a three tiered proteomic and drug discovery strategy:

The first tier is to differentially compartmentalize functional characteristics that can be signature profiled, compared and enriched.

The second tier pre-supposes that the first tier has been successful in establishing disease-specific active site variants, and these can compartmentalized for challenge with small molecules.

The third tier is to perform small molecule selectivity screening based on the kinetics of active site variants, - a new drug discovery paradigm.

ProFACT is advancing this strategy towards cAMP hydrolysis (Phosphodiesterase activity), Kinase activity, Protease activity (especially Proteasome) and p53 variants, but the platform technologies can be applied towards any measurable functional or enzyme activity.

Unique and proprietary to ProFACT, these combined deliverables will provide an exceptional new approach to accelerate drugs to market. Functional Proteome Prospecting™ can be used to isolate or purify important drug targets. Conformerics™ will integrate these targets within drug screening assays.

SeraFILE™-derived enzymatic activity profiles provide a means to detect disease-specific conformers and compartmentalize them for drug screening purposes.

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Proteasome chymotryptic activity increased significantly in cancer samples in most sub-fractions, for breast (A) and esophageal cancer (data not shown), compared to normal adjacent tissue (the control). Red arrows indicate enhanced proteasome activity in a few notable sub-proteomes compared to control extracts (for instance flow-through fractions from matrix 1 and 11; B). Such compartmentalized activity may serve as biomarkers or potential drug targets.

In this example, compartmentalized conformers can be challenged with small molecule inhibitors demonstrating that inhibitor efficiency changes with the conformational status.

SeraFILE� compartmentalized conformers

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Unique experiences.

Tony Fred, CEO

Founder and chief visionary, Tony is the driving force behind the company. He loves to keep his hands full by participating in the development of the software, marketing, and customer experience strategies.

Mich Stark, COO

Mich loves taking on challenges. With his multi-year experience as Commercial Director in the software industry, Mich has helped the company to get where it is today. Mich is among the best minds.

Aline Turner, CTO

Aline is one of the iconic people in life who can say they love what they do. She mentors 100+ in-house developers and looks after the community of thousands of developers.

Iris Joe, CFO

Iris, with her international experience, helps us easily understand the numbers and improves them. She is determined to drive success and delivers her professional acumen to bring the company to the next level.