# Leap: molecular synthesisability scoring with intermediates

arXiv: https://arxiv.org/abs/2403.13005 · HTML: https://mlsanity.com/paper/2403.13005/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 5 of its 20 references that are in the map.
- First posted on arXiv 14 Mar 2024.

## Builds on (most cited first, 5 of 5)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Prediction](https://mlsanity.com/paper/1811.02633/) (2018)
- [Learning to Plan Chemical Syntheses](https://mlsanity.com/paper/1708.04202/) (2017)
- [The Synthesizability of Molecules Proposed by Generative Models](https://mlsanity.com/paper/2002.07007/) (2020)
- [Amortized Tree Generation for Bottom-up Synthesis Planning and Synthesizable Molecular Design](https://mlsanity.com/paper/2110.06389/) (2021)

## Abstract (arXiv)

Assessing whether a molecule can be synthesised is a primary task in drug discovery. It enables computational chemists to filter for viable compounds or bias molecular generative models. The notion of synthesisability is dynamic as it evolves depending on the availability of key compounds. A common approach in drug discovery involves exploring the chemical space surrounding synthetically-accessible intermediates. This strategy improves the synthesisability of the derived molecules due to the availability of key intermediates. Existing synthesisability scoring methods such as SAScore, SCScore and RAScore, cannot condition on intermediates dynamically. Our approach, Leap, is a GPT-2 model trained on the depth, or longest linear path, of predicted synthesis routes that allows information on the availability of key intermediates to be included at inference time. We show that Leap surpasses all other scoring methods by at least 5% on AUC score when identifying synthesisable molecules, and can successfully adapt predicted scores when presented with a relevant intermediate compound.