Significant progress has been made in using the central nervous system multiparameter optimization (CNS MPO) approach to rationally design molecules. Diseases of CNS present a large area of medical need. An easy-to-use design algorithm has expanded the design space for CNS drug candidates and further demonstrated the advantages of using a flexible multi-parameter method in drug discovery rather than individual parameters and hard cutoff values of physicochemical properties. As a result, the CNS MPO algorithm enables to help improve the priority of design concepts and the quality of compounds nominated for clinical development.
BOC Sciences has applied the CNS MPO function in the construction of CNS MPO library to accelerate the identification of compounds with increased probability of success.
Figure 1. CNS MPO Desirability. (Wager, T. T.; et al. 2017)
Advantages of CNS MPO Library
- Significantly increase the number of compounds available for clinical development that exhibit consistent ADME properties, cross the blood-brain barrier, and reside in a low-risk safety space
- Reduce the number of compounds submitted to toxicity studies
- Increase the number of drug candidates
CNS MPO Library Design
Drug discovery within CNS area has specific and unique demands for physicochemical and structural properties of comounds:
- Permeate the blood-brain barrier
- Be less polar, smaller and more rigid than non-CNS molecules
- Have strong constraints on the number and/or type of functional groups
- MPO score obtained by adding individual desirability scores for each property:
- Focus on novelty
- Application of modified MPO
- Desirability thresholds for ClogP, clogD7.4, HBD, pKa
- Custom lead-like desirability thresholds for MW, PSA
- Custom diversity clustering
Figure 2. CNS MPO desirability scores for candidates, CNS MPO candidates, and drugs. (Wager, T. T.; et al. 2017)
CNS MPO Library Characteristics
BOC Sciences’ CNS MPO library includes nearly 9,000 therapeutically relevant compounds that are carefully selected from our proprietary collection of HTS compounds to meet the parameters listed in the table below.
Table1. The summary of the BOC Sciences CNS MPO Library characteristics
| Parameter | Value |
| MW | 150-500 |
| LogP | -2-4 |
| TPSA | 20-140 Å2 |
| Number of H Donors | ≤2 |
| Number of H Acceptors | ≤8 |
| Number of Rotatable bonds | ≤4 |
| Number of Rings | 1-6 |
| Fsp3 | 0.3-1 |
| ClogP | -0.5-3 |
| Number of H-bonding | ≤8 |
| Number of Carboxylic acid group | ≤1 |
| Number of Amide groups | ≤1 |
| CNS MPO | ≥4 |
| Number of Aromatic rings | 1-3 |
| QPPCaco-2 | ≥500 |
| Basic N | ≤2 |
| QPlogBB | -1-0.8 |
| CNS | ≥1 |
| pKa bs | -1.5-8 |
- All PAIN and reactive compounds are excluded from selection by internal filter applications
- Structurally diverse subset, with the option to favor hit discovery
- Structural analogs available for SAR studies
- All compounds are continually updated
- Compound cherry-picking service is available
What We Deliver
- Delivered within 2 weeks in any customer-preferred format
- Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
- All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of CNS MPO Library design at competitive prices for global customers. Personalized and customized services of CNS MPO Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Wager, T. T.; et al. Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery. Acs Chemical Neuroscience. 2016: 7(6): 767-775.
