The incidence of central nervous system (CNS) diseases is currently increasing at an alarming rate. Although scientists have conducted extensive research efforts to develop new CNS-active drugs, most CNS disorders pose significant clinical challenges. Drug delivery to the CNS is complicated by blood-brain barrier (BBB), which controls drug entry into the CNS. BBB is one of the most important factors limiting the development of drugs specifically targeting brain disorders. It has been demonstrated that the blood-brain barrier penetration of molecules depends on their molecular weight (MW), charge and lipophilicity. Moderately lipophilic drugs cross the BBB by passive diffusion, while polar molecules do not penetrate well into the CNS.
Since the high-throughput screening (HTS) technique has been introduced to BOC Sciences, our teams have proposed a number of methods to identify compounds with good BBB penetration based on their physicochemical properties. Our proprietary CNS compound library is designed as a special screening library containing compounds with high BBB permeability. The library contains 1,735 compounds with physicochemical properties that are preferably used for BBB permeation and are also suitable for oral administration.
Figure 1. Genome-wide genetic screening in the mammalian CNS. (Mary, H.; et al. 2017)
CNS Screening Library Design
CNS Screening Library Characteristics
BOC Sciences’ CNS screening library includes nearly 9,900 structurally diverse compounds with CNS penetrant properties 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 screening library characteristics
| Parameter | Value |
| MW | 150-400 |
| ClogP | 1.3-3.0 |
| TPSA | ≤ 65 Å2 |
| Number of H Donors | ≤3 |
| Number of H Acceptors | ≤6 |
| Number of Rotatable Bonds | ≤6 |
| Number of Rings | 1-5 |
| Number of Total H-bonding | <8 |
| Number of Carboxylic acid group | ≤1 |
| Number of S atoms | ≤2 |
| Number of Cl atoms | ≤2 |
| Number of Basic Nitrogen | ≤ 2 |
| Number of Quaternary nitrogen | 0 |
| MPO Score | ≥4 |
Features of CNS Screening Library
- All PAIN and reactive compounds are excluded from selection by internal filter applications
- The following compounds are carefully removed from the CNS screening library :
Compounds with carboxyl group
Compounds with reactive groups
biologically unstable compounds
compounds difficult for optimization
compounds containing any atom different to O, N, C, H, Br, I, Cl, F, or S
- We perform additional CNS multiparameter optimization
- High quality lead-like, small molecule compounds for CNS focused drug discovery
- High probability of BBB penetration with improved clearance and safety using CNS calculations
- Structurally diverse subset, with the option to favor hit discovery
- Structural analogs available for SAR studies
- Synthetic macrocycles with potential applications for CNS drug discovery
- Extensive conformational analysis for calculating adjusted CNS scores in lipophilic solvent
- 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 Screening Library design at competitive prices for global customers. Personalized and customized services of CNS Screening 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
- Mary, H.; et al. Genome-Wide Genetic Screening in the Mammalian CNS. Genome Editing in Neurosciences. 2017. 15: 31-39.
