matched pairs Leach

Presenters at medicinal chemistry conference now use the phrases ‘matched pairs’ and ‘matched pair analysis’, showing the technique has become a ‘must-have’ part of the analysis toolbox. Choosing which matched pair papers to feature in #BucketListPapers was surprisingly difficult, given this is our area of expertise. We have chosen one of the first papers in the area:

Matched Molecular Pairs as a Guide in the Optimization of Pharmaceutical Properties; a Study of Aqueous Solubility, Plasma Protein Binding and Oral Exposure

J. Med. Chem., 2006, 49 (23), 6672-6682

For a review of the techniques and the literature, a book chapter is now available:

Matched Molecular Pair Analysis. Andrew Leach

Comprehensive Medicinal Chemistry III, Volume 3 page 221.

The field has advanced due to efficient and reproducible algorithms being published. Here are two key references:

Computationally Efficient Algorithm to Identify Matched Molecular Pairs (MMPs) in Large Data Sets

J. Chem. Inf. Model. 2010, 50, 339–348 

WizePairZ: A Novel Algorithm to Identify, Encode, and Exploit Matched Molecular

Pairs with Unspecified Cores in Medicinal Chemistry

J. Chem. Inf. Model. 2010, 50, 1350–1357

Matched Molecular Pair Analysis can be used to share knowledge between organisations without sharing the original chemical structures and data.

Learning Medicinal Chemistry Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) Rules from Cross-Company Matched Molecular Pairs Analysis (MMPA)

J. Med. Chem. 2018, 61, 3277−3292

..and it can be combined with Machine Learning…

Coupling Matched Molecular Pairs with Machine Learning for Virtual Compound Optimization.

J. Chem. Inf. Model. 2017, 57, 12, 3079–3085

#BucketListPapers #DrugDiscovery #MedicinalChemistry #BeTheBestChemistYouCanBe