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 UPDATED! The library has been just updated!
The central purpose of this specially designed Fragment Library is to provide
fragments that will bind to the binding site(s) of any target and will also provide suitable starting points for drug discovery. Strict structural, substructural and special medicinal chemistry filters were applied for the library preparation.
Fragment-based lead discovery (also referred to as needles, shapes, binding elements, seed templates or scaffolds) is a new lead discovery approach in which much lower molecular weight (100-300Da) compounds are screened relative to HTS campaigns. Fragment-based hits are typically weak inhibitors (10μM-mM), and therefore need to be screened at higher concentration using very sensitive biophysical detection techniques such as protein crystallography and NMR as the primary screening techniques, rather than bioassays. Compared with HTS hits, these fragments are simpler, less functionalized compounds with correspondingly lower affinity. However, fragment hits typically possess high ‘ligand efficiency’ (binding affinity per heavy atom) and so are highly suitable for optimization into clinical candidates with good drug-like properties.
The OTAVAchemicals General Fragments Library, comprising 13,685 compounds, has been designed based upon the commonly accepted "Rule-of-Three" and other physicochemical and structural properties. Compounds were filtered on molecular weight (MW ); number of H-bond donors ≤ 3; hydrophobicity as the calculated octanol/water partition coefficient (cLogP ); number of rotatable bonds ≤ 3; number of H-bond acceptors ≤ 4 (the increased number of acceptors in the library was applied to satisfy a kinase binding pharmacophore); molecular polar surface area (PSA < 80); calculated aqueous solubility (LogSW > -5) (high aqueous solubility is essential for practical reasons during screening particularly in HCS).
The following compounds were REMOVED from the library:
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compounds containing any atom different to O, N, C, H, Br, I, Cl, F, S, or P
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compounds that do not contain at least one aliphatic or aromatic ring.
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compounds containing more than 4 halogen atoms
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compounds containing reactive functional groups bearing the risk of covalent binding to the target protein
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compounds containing functionalities that can cause undesirable effects such as: Cancerogenic, Toxicity, ADME problems, False positives
All compounds are in stock, cherry-picking is available.
The summary of the OTAVAchemicals General Fragments Library characteristics:
|
Parameter |
Value |
Average |
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MW |
< 300 |
221 |
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CLogP |
< 3 |
1.72 |
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Number of Rotatable Bonds |
≤ 3 |
1.84 |
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Number of H Donors |
≤ 3 |
0.98 |
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Number of H Acceptors |
≤ 4 |
2.7 |
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PSA |
< 80 |
52.3 |
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Number of Rings |
> 0 |
2 |
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LogSw |
> -5 |
-2.66 |
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Sum of Halogen Atoms |
≤ 4 |
0.34 |
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Compounds with "undesirable" functionalities |
Removed |
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Compound amount in stock |
> 10mg |
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Fsp3 |
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28,8% |
On your request our experts will choose functionalities as appropriate groups to allow rapid chemistry to be applied to the fragments for evolution of the compounds. Custom parameter filtering is also possible.
The library (SDF, XLS, PDF format) is available on request. Feel free to contact us or use on-line form below to send an inquiry if you are interested to obtain this library or if you need more information.
Fragment-based lead discovery: leads by design. Carr RA, Congreve M, Murray CW, Rees DC. Drug Discov Today. 2005 Jul 15;10(14):987-92
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