CNS MPO Library

Description

The CNS MPO Library is the largest commercially available diversity set, specifically designed for Central Nervous System (CNS) drug discovery designed through employment of Multi-Parameter Optimization to enhance Blood-Brain Barrier (BBB) permeability. It comprises 28,284 compounds.

Key Characteristics of the CNS-Specific Small Molecule Library for Enhanced Drug Discovery

●      Distinctive chemistry with significant intellectual property potential.

●      CNS-focused Gentle Multi-Parameter Optimization (gMPO) strategy for selecting compounds with enhanced Blood-Brain Barrier permeability, including:

●      Emphasis on molecules with Markush novelty.

●      Application of modified MPO and pMPO systems.

●      Specific desirability thresholds for physicochemical properties such as cLogP, cLogD7.4, hydrogen bond donors (HBD), and pKa.

●      Customized lead-like desirability thresholds for molecular weight (MW) ranging from 280 to 400.

●      Customized lead-like desirability thresholds for polar surface area (PSA) between 60 and 80.

●      Unique diversity clustering approach.

●      Restriction to only one hydrogen bond donor per compound.

●      Limitation to no more than one strongly basic amine.

●      Exclusion of free carboxylic acid functionality.

●      Avoidance of undesirable chemical functionalities, including electrophilic groups, acid labile groups, toxicophoric groups, and Pan-Assay Interference Compounds (PAINS) structural fragments.

Publications

• Gunaydin, H. (2016) Probabilistic Approach to Generating MPOs and Its Application as a
Scoring Function for CNS Drugs ACS Med. Chem. Lett. 7, 89-93
• Hitchcock, S.A. (2012) Structural Modifications that Alter the P-Glycoprotein Efflux
Properties of Compounds J. Med. Chem. 55, 4877-4895
• Design of a Focused CNS Screening Collection at Takeda (2016) UK-QSAR and
Cheminformatics Group/Physchem Forum Meeting
• Mayol-Llinàs, J. et al. (2017) Assessing molecular scaffolds for CNS drug discovery. Drug
Discov. Today. 7, 965-969
• Wager, T.T. et al. (2016) Central nervous system multiparameter optimization desirability:
Application in drug discovery. ACS Chem. Neurosci. 7, 767-775
• Rankovic, Z. (2015) CNS drug design: balancing physicochemical properties for optimal
brain exposure. J. Med. Chem. 58 (6), 2584–2608