Classification of matching molecular series on the basis of sar. Using advanced matched molecular pair analysis mmpa, we combined data from three pharmaceutical companies and generated admet rules, avoiding the need to disclose the full chemical structures. Evaluating the differences in cycloalkyl ether metabolism using the design parameter lipophilic metabolism efficiency lipmete and a matched molecular pairs analysis. Such pairs of compounds are known as matched molecular pairs mmp. Matched molecular pairs mmps are widely used in medicinal chemistry to study changes in compound properties which. Significance and the impact of experimental uncertainty. Molecular matched pair mmp analysis has been used for more than 40 years within.
Current topics in medicinal chemistry, volume 14 number 7. Matched molecular pair analysis of activity and properties. Extracting medicinal chemistry knowledge by a secured matched. Journal of medicinal chemistry 20, 56 17, 69856990. A multipharma med chem textbook based on a thorough ai study. The first large scale analysis of in vitro absorption, distribution, metabolism, excretion, and toxicity admet data shared across multiple major pharma has been performed. In medicinal chemistry, matched molecular pairs mmps have experienced. For graphical sar analysis, the mmp concept has been further extended by. Matched molecular pair analysis mmpa is a method in cheminformatics that compares the properties of two molecules that differ only by a single chemical transformation, such as the substitution of a hydrogen atom by a chlorine one. Matched molecular pair analysis of activity and properties of glycogen phosphorylase inhibitors. He has years of experience in medicinal chemistry spread across oncology hormonal and kinase inhibitors, inflammation oa and ra, enzyme inhibitors, and gpcr targets, and diabetes obesity, gpcr, and enzyme inhibitors. A medicinal chemistry perspective on melting point. Multiple parameter optimisation in drug discovery is difficult, but matched molecular pair analysis mmpa can help.
Join editorial board book proposal become an executive guest editor thematic issue proposal. In 2012, he cofounded medchemica limited to use matched molecular pair analysis to accelerate medicinal chemistry. To achieve this, we performed matched molecular pairs analysis mmpa on the stability data measured in mouse and human cytosol fractions. Algorithms to extract structure matched molecular pair analysis all combinations considered. Matched molecular pair analysis mmpa has proven to be a powerful tool to rationalize and predict many aspects of structureactivity relationships sars within a series of analogues. Computer algorithms can process data in an unbiased way to yield design rules and suggest better molecules, cutting the number of design cycles. Using matched molecular series as a predictive tool to. One way to sample chemical space is through matched pair analysis. Matched molecular pairs as a medicinal chemistry tool. Matched molecular pair analysis mmpa is a method in cheminformatics that compares the. A novel algorithm to identify, encode, and exploit.
The term was first coined by kenny and sadowski in the book chemoinformatics in drug discovery. Recent applications, synthetic advances and matchedpair analyses. A matched molecular pair analysis of in vitro human microsomal. A matched molecular pair analysis mmpa was used to study the classic medicinal chemistry transformation of a disubstituted benzene into a heterocyclic ring. He has years of experience in medicinal chemistry spread across oncology. This concept is widely applied in medicinal chemistry due.
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