TECHNOLOGY
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If we wish to mine the territory of the undruggable proteome and develop drugs that target currently undruggable targets, we need to think -and act - beyond the key-lock principle: design small chemical drugs that dock onto rigid docking sites (pockets) within the structured proteins with well-known roles in diseases. Instead, to look beyond the proverbial are around the lamppost as in current pharma, we first must embrace a new chemistry, so as to target proteins that are not structured or those that act by forming large protein complexes or even condensates. We also must consider the type of discovery processes that do not start from a specific validated target - but with a new well-defined phenotype, without necessarily knowing the identity of target to be acted upon to modulate said phenotype.
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P4BIOS implements these two new philosophies combined into one discovery platform using latest technologies.
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A validated target protein is the starting point -
and one assumes that biology can be operated by blocking one such target molecule at a time.​​
P4BIOS embraces both philosophies of drug-screening:
(1) target-focused approach where appropriate (target is a well validated bio-regulatory natural molecular lever-point, such as receptors)
(2) phenotype-focused approach, seeking molecules that reprogram cells or tissue states via concerted action on multiple pathways.
Small chemical compound libraries have a diversity of typically <10^8 species, each one of which, unless DNA-encoded,
must be kept in separate vials
P4BIOS has developed a proprietary synthesis of libraries of "neo-peptide" that act as shape-shifters. The method and is scalable to produce a diversity of up to 10^12 molecular species
Biochemical screen for binding to target: cumbersome -
often requiring high-throughput liquid-handling robotics and
the macro-biological consequence of binding is often unpredictable.
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P4BIOS has established a one-shot ultra-massively parallel, AI-supported single-cell resolution screening of 100 millions of molecules in live cells that report "hits" of its genetically encoded molecules when they
(1) bind to intended target or
(2) activate the actual desired phenotypic effect