The Open PHACTS Discovery Platform links the large amounts of physicochemical and pharmacological data available in public databases, and provides a means of querying this via the Open PHACTS Explorer, the Open PHACTS API and applications. The number of pharmacological questions that could foreseeably be useful to answer is large, and Open PHACTS concentrates on answering the top 20 ranked research questions from a list of 83 proposed by consortium members (table below). These questions can be grouped as Cluster I and Cluster II. The first cluster asks basic pharmacology questions, which are typically asked in the early stages of drug discovery, regarding interactions between a compound or compound group and defined targets. The second cluster asks questions of compound-target interactions, but also extends the query to pathways and diseases. Such questions typically require associated references as they are useful in the lead optimisation phase or for proof of concept studies. Another important concept in the Open PHACTS Discovery Platform is that of data provenance. Allowing the identification of data origins is a vital factor in developing end-user trust.
All oxidoreductase inhibitors active at <100 nM in both human
Given compound X, what is its predicted secondary pharmacology?
What are the on- and off-target safety concerns for a compound?
What is the evidence and how reliable is that evidence
(journal impact factor, KOL) for findings associated with a compound?
Given a target find me all actives against that target.
Find/predict polypharmacology of actives. Determine ADMET profile
|Q4||For a given interaction profile, give me compounds similar to it.|
The current Factor Xa lead series is characterized by substructure X.
Retrieve all bioactivity data in serine protease assays for
molecules that contain substructure X.
A project is considering Protein Kinase C Alpha (PRKCA) as a target.
What are all the compounds known to modulate the target directly?
What are the compounds that may modulate the target directly?
i.e. return all compounds active in assays
where the resolution is at least at the level of the target family (i.e. PKC)
both from structured assay databases and the literature.
Give me all active compounds on a given target with the
relevant assay data.
|Q8||Identify all known protein-protein interaction inhibitors.|
|Q9||For a given compound, give me the interaction profile with targets.|
|Q10||For a given compound, summarize all ‘similar compounds’ and their activities.|
Retrieve all experimental and clinical data for a given list of compounds
defined by their chemical structure
(with options to match stereochemistry or not).
For my given compound, which targets have been patented in the context of
What ligands have been described for a particular target associated
with transthyretin related amyloidosis, what is their affinity for that target,
and how far are they advanced into preclinical / clinical phases,
with links to publications / patents describing these interactions?
Target druggability: Compounds directed against target
X have been tested in what indications?
What new targets have appeared recently in the
patent literature for a disease? Has the target been screened
in AstraZeneca before? What information on in vitro
or in vivo screens has already been performed on a compound?
What chemical series have been shown to be active against target X?
What new targets have been associated with disease Y?
What companies are working on target X or disease Y?
What compounds are known to be activators of targets
which relate to Parkinson’s Disease or Alzheimer’s Disease?
For my specific target, which active compounds have been reported
in the literature? What is also known
about upstream and downstream targets?
Compounds that agonizes targets in pathway X assayed
in only functional assays with a potency <1 ?M.
Give me the compound(s) which hit most specifically the multiple targets
in a given pathway (disease).
For a given disease/indication, give me all targets
in the pathway and all active compounds hitting them.