Blood-Brain Barrier (BBB) Score Predictor

    The following manual gives you a walk-through on how to use the BBB Score Predictor.

    Table of Contents

    Introduction

    The blood-brain barrier (BBB) is a crucial part of the human central nervous system (CNS). It is a cell layer functioning as a protective barrier for the brain against possible pathogenic organisms. It also regulates the transport of different molecules into the brain, including nutrients necessary for neural function, ions and drugs.

    This barrier plays an important role in the design of drugs because CNS-targeted compounds should cross the BBB to reach a certain therapeutic level in the brain tissue. However, high levels of non-CNS drugs appearing in the brain can cause unwanted side effects, making the BBB penetration a distinctive feature for CNS targeting.

    To understand the BBB penetration of drugs, Gupta et al. studied their physico-chemical property spaces and developed a score (called BBB Score) to predict if a drug is preferentially CNS or non-CNS active.

    The BBB Score is composed of 5 physico-chemical descriptors: the number of aromatic rings, the number of heavy atoms, MWHBN (a descriptor calculated from the molecular weight and the number of H-bond donor and acceptor atoms), the topological polar surface area (TPSA) and the pKa. The final score is calculated using stepwise (for descriptors with purely discrete values) and polynomial weight functions (for descriptors having continuous ranges).

    The research revealed that (tested on a set of 270 CNS and 720 non-CNS drugs) the BBB Score (a number between 0 and 6) is a distinctive predictor of CNS drug-likeness. Molecules with BBB Scores between 0 and less than 4 can be classified as non-CNS drugs, while molecules with BBB Scores between 4 and 6 can be classified as CNS drugs.

    Chemaxon's BBB Score Predictor is able to predict the BBB Score based on the formula published by Gupta et al.

    Availability

    The BBB Score prediction has been available since v. 22.21 in the following Chemaxon products.

    MarvinSketch

    In MarvinSketch the BBB Score prediction is available under the Calculations » Other » BBB score menu item.

    bbb_score_marvin

    cxcalc

    Use the bbb function to predict the BBB Score with cxcalc:

    cxcalc -N ih bbb sildenafil
3.05

    Chemical terms

    Use the bbb() function to predict the BBB Score with Chemical Terms:

    evaluate -e "bbb()" sildenafil
3.05

    API

    The BBB Score prediction is also available via the public Java API and the Calculations Web Services API.

    Accuracy report

    We tested the BBB Score Predictor on a test set of 269 molecules available in the reference. The table below shows the number of test molecules for which the predicted BBB Score falls within the delta range of 0-0.5 and 0.5-1.0, respectively.

    Range Number of compounds (269 in total)
    0.0-0.5 267
    0.5-1.0 2

    Licensing

    The BBB Score is a composite score and therefore its calculation requires Protonation and Structural Calculations licenses.

    NOTE: Predicting the BBB Score in MarvinSketch requires ONLY the MarvinBeans license. In other Chemaxon tools it requires the mentioned licenses above.

    References

    1. Gupta, Mayuri et al. (2019). The Blood-Brain Barrier (BBB) Score, J. Med. Chem. 2019, 62(21), 9824–9836. https://doi.org/10.1021/acs.jmedchem.9b01220