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Properties and Profile of the Maybridge Screening Collection
Our Maybridge screening collection comprises structures with complex and diverse properties. Lipinski’s Rule of 5 is widely considered in medicinal chemistry to be a preliminary measure of a compound’s likelihood to be an orally active drug in humans. The Rule of 5 notes the parameters listed below as crucial for consideration during drug discovery. Here, we provide the calculated distribution of our Maybridge screening collection for each parameter.
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Molecular weight
The ideal molecular weight of a drug compound is less than 500 Daltons. The Maybridge screening collection is composed primarily of compounds that fall within this ideal range.
H-bond acceptors
Compounds containing a maximum of 10 H-bond acceptors are more likely to be orally active in humans. Every structure in our screening collection has 8 H-bond acceptors or fewer.
H-bond donors
Compounds containing a maximum of 5 H-bond donors are more likely to be orally active in humans. Each structure in our screening collection has 5 H-bond donors or fewer.
Partition coefficient (cLogP)
The calculated partition coefficient (cLogP) provides an insight to the solubility of a compound. This is a critical consideration as drugs must navigate both hydrophobic and hydrophilic environments to reach their targets. Compounds should have cLogP values less than 5, and our Maybridge screening collection is composed primarily of structures that fall within the ideal range.
Rotatable bonds
Compounds containing a maximum of 10 rotatable bonds are more likely to be orally active in humans. Over 90% of our screening collection contain 10 or fewer rotatable bonds.
All calculations were performed at Maybridge using the Tsar 3D version 3.3 from Accelrys (salt data was ignored). Definitions from the Tsar Reference Guide are provided below.
- H-bond acceptors are defined as accepting a lone pair of electrons to form a hydrogen bond: –O–, C=O, –CN, –N=, 3° amines (excluding sp2), SH, or C=S.
- H-bond donors are defined as O-H, N-H, and S-H bonds where atoms donate a lone pair of electrons to form a hydrogen bond.
- cLogP is defined as the sum of the atomic partial log P values. (6)
- Rotatable bonds are defined as any single order, non-terminal, non-ring, and non-amide bond.
Properties of Maybridge screening compounds
An independent study carried out by McGregor and Pallai comparing the diversity of 10 commercially available libraries and the Available Chemicals Directory (ACD) showed that out of the libraries that were produced in-house, Maybridge had the most diverse library, i.e., the most singletons (clusters with one member) and the highest number of clusters. (1)
When mapped against the World Drug Index (WDI), it was shown that the Maybridge Screening Collection expresses ~87% of the 400,000 theoretical drug pharmacophores*, indicating a far-reaching coverage of active moiety space which enables generation of a high impact in screening programs. (*Calculations carried out by Oxford Molecular using Chem-X definition, i.e., triplets of H-bond acceptors, H-bond donors, aromatic ring centers, and positive nitrogen atoms.)
The compounds in the Maybridge collection generally obey Lipinski's "Rule of Five". (2)
| Lipinski | Maybridge screening collection |
|---|---|
| <5 H-bond donors | 99.7% <5 |
| <10 H-bond acceptors | 99.8% <10 |
| cLogP <5> | Mean logP 3.23, 94% in range -0.11 to 6.3 |
| Mol. wt. <500> | Mean mol. wt. 325, 95% in range 150–500 |
The compounds in the Maybridge collection generally demonstrate good ADME (absorption, distribution, metabolism, and excretion) profiles, which make them ideal candidates for development beyond the initial screening assay.
ADME calculations:
HIA (human intestinal absorption) good/poor cutoff set at 40%. (3)
BBB (Blood-Brain Barrier) BBB+ ≥–0.2, BBB– ≤–0.5, BBB+/– borderline. (4,5)
The Maybridge collection compounds are of high quality, based on the analysis of screening compounds by appropriate methodologies including:
- Nuclear magnetic resonance spectroscopy (NMR)
- Infrared spectroscopy (FT-IR)
- Liquid chromatography-mass spectrometry (LC-MS)
- High performance liquid chromatography (HPLC)
- Elemental analysis
The purity of the screening collection, unless stated, is greater than 90%, with most compounds having a purity of 95%.
Reactive molecules are excluded in order to reduce the number of false positives. Learn more about our false positives exclusion criteria.
Typically, about 95% of the compounds in our collection are available in >5 mg stock quantities and over 90% of the compounds are available in >50 mg stock quantities. A large proportion of our collection is available in gram quantities. This means we can ensure a very high level of re-supply of originally tested compounds. We provide most major brands of plates and vials but are happy to use those supplied by customers on request.
References
- The Journal of Chemical Information and Computer Sciences 1997,37,443-448.
- Lipinski, C.A., Lombardo, F., Dominy, B.W. and Feeney, P.J. (1996). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 23 3-25.
- J. Pharm. Sci., 2001, 90, p749.
- Eur. J. Med. Chem., 2001, 36, p719.
- J. Med. Chem., 2000, 43, p2204.
- Viswandhan, VH, Ghose, AK, Revankar, GR, et al. J. Chem. Inf. Comput. Sci., 1989, 29, 163-172.
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