The following manual gives you a walk-through on how to use the CNS MPO Score Predictor.
Central Nervous System (CNS) drugs are special in the sense that they have to penetrate the Blood-Brain Barrier (BBB) in order to have any effect on their target. It is also known that they exhibit physico-chemical properties from certain ranges, forming a smaller subset in the large property space of orally available drugs.
Wager and his co-researchers at Pfizer built a CNS Multiparameter Optimization (MPO) algorithm for generating a score that used 6 common physico-chemical properties (molecular weight (MW), logP, logD at pH 7.4, topological polar surface area (TPSA), the number of H-bond donors (HBD) and the pKa of the most basic center of the molecule) to build a relationship between this smaller CNS property space and CNS drug-likeness. The research revealed that CNS drugs already on the market and potential candidates show high MPO score values (so called desirability score values ≥ 4.0 on a scale between 0 and 6), making this a useful tool at the design stage to accelerate the identification of compounds with increased probability of success. Since the publication of the research the CNS MPO Score has become a generally accepted algorithm in the CNS-oriented medicinal chemistry community.
Chemaxon's CNS MPO Score Predictor is able to calculate the CNS MPO score using the algorithm published by Wager et al.
The CNS MPO Score prediction has been available since v. 20.21. in the following Chemaxon products.
In MarvinSketch the CNS MPO Score prediction is available under the Calculations » Other » CNS MPO score menu item.
To predict the CNS MPO Score with cxcalc, use the mpo function:
cxcalc -N ih mpo aspirine 5.75
To predict the MPO Score with Chemical Terms, use the mpo() function:
evaluate -e "mpo()" aspirine 5.75
We tested the CNS MPO Score Predictor on a test set of 119 molecules available in the references. We plotted the number of test molecules for which the predicted CNS MPO score falls within the delta range of 0-0.5, 0.5-1.0 and 1.0-1.5, respectively.
The CNS MPO Score is a composite score and therefore its calculation requires Protonation, Partitioning and Structural Calculations licenses.