Analog Accessibility Score (AAscore) for Rational Compound Selection
2024

Analog Accessibility Score for Compound Selection

Sample size: 1000 publication 10 minutes Evidence: moderate

Author Information

Author(s): Ue Takato, Sato Akinori, Miyao Tomoyuki

Primary Institution: Nara Institute of Science and Technology

Hypothesis

Can an analog accessibility score (AAscore) effectively represent the accessibility of analog compounds for a given input compound?

Conclusion

The AAscore can objectively assess the accessibility of analog compounds for a target compound, although it showed little correlation with the number of synthesized analogs.

Supporting Evidence

  • The AAscore is defined as the number of unique analogs generated through retrosynthesis and forward prediction.
  • A case study showed that the AAscore could identify compounds synthesized into analogs.
  • The AAscore was significantly influenced by the number of extracted candidate reactants from a reactant database.

Takeaway

The AAscore helps scientists find similar compounds that can be made easily, which is important for drug development.

Methodology

The AAscore was calculated by decomposing input compounds into potential reactants, replacing the smallest reactant with candidate reactants from a database, and generating products through forward prediction.

Potential Biases

The AAscore may not accurately reflect the true accessibility of analogs due to limitations in the retrosynthesis approach.

Limitations

The AAscore relies on the accuracy of the prediction models and the quality of the compound database used for candidate reactants.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1021/acs.jcim.4c01691

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