Tuesday, 19 August 2008
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| Boston | Delft | Tokyo | ||
SMALL MOLECULES!
Pyxis Discovery provides chemistry-based lead discovery services to companies that are active in small molecule drug discovery.
Our Smart Approach for designing and selecting screening compound libraries facilitates a rapid and efficient lead discovery process, yielding lead compounds with excellent pharmacological profiles.
Our services include:
In the October 2006 issue of Molecular Diversity, one of the leading cheminformatics publications in drug discovery, an analysis performed by Pyxis Discovery can be found.
The full reference of the paper is: Verheij, H.J., Molecular Diversity 10 (2006), 3, 377-388. The online publication can be obtained by clicking here.
Click here for an overview of the upcoming events that Pyxis Discovery will attend.
Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus Anthracis. ALF (Anthrax Lethal Factor) is an integral component of the anthrax toxin. The toxin, after it is released from the bacterium, acts in unison in inducing cell death of the host organism. Due to the increased threat of bioterrorism using anthrax, there is a growing need for novel and efficient drugs for the protection of the civil population.
Pyxis Discovery is involved in a project to discover novel inhibitors of ALF. We have designed a small diverse library of novel leadlike molecules, capturing some of the features of known ALF inhibitors. This library has been screened both in an enzymatic assay as well as a cellular assay.
We have identified some new classes of compounds with submicromolar activity in the enzymatic assay and micromolar activity in the cellular assay. We have benchmarked our compounds against some of the reported ALF inhibitors from literature and found that several of our compounds show higher inhibitory effects in our screening assays.
Currently, Structure Activity Relationships are being established.
Target Immobilized NMR Screening (TINS) is one of the latest developments in fragment based screening. Just like any other of these techniques, it requires a well-tuned library of fragments in order to obtain a diverse set of screening hits.
For one of the drug discovery projects in which Pyxis Discovery is involved, we have selected a set of 2,000 fragments, based on 4 different design approaches. The structures have been filtered for undesired functionalities, using an in-house designed set of structural filters that encodes for leadlikeness. A small set of preferred functional groups (polar or hydrophobic) was also filtered for, in order to both enhance binding properties and follow-up synthetic possibilities of the fragments.
This set of compounds was finally selected for maximum scaffold diversity using Xu's 'Scaffold-based Classification Approach', a method that clusters compounds based on the complexity of their scaffold.
The fragments are available for screening at ZoBio (Leiden, The Netherlands), using their TINS platform.
