The "Guideline of Two" Over the past decade, a number of rules and calculated metrics have arisen in drug discovery. In particular, the Rule of Three (RO3) is most commonly used as a filter to generate a "fragment library" from a larger compound collection. However: Rules evolve over time to reflect data and experiences Issues can arise from universally applying rules to all situations Emerging data has shown that a simple filter of compound libraries to generate a "RO3 frag