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Sequencing of the human genome at the turn of the 21st century promised a new era of opportunities for pharma, raising expectations as well as R&D expenditure.
While there’s certainly a case for adopting a more nuanced and pragmatic approach to applying Lipinski’s rules, the Waring study shows that the principles underpinning them still shape success.
Bringing together data from multiple pharmaceutical companies, these investigations have revealed some interesting findings.
A recent study by Waring and colleagues analyzed the main causes of attrition in drug development based on a review of 812 NCEs under development by Astra Zeneca, Eli Lilly, Glaxo Smith Kline and Pfizer.
In fact, although a number of approved NCEs violated either the molecular weight or calculated log P rule, only 8% of drug candidates violated both.
Overall, NCEs that gain approval tend to be smaller, less lipophilic, have rotational flexibility and have fewer carbon aromatic rings.