# Conditioned Generative Modeling of Molecular Glues: A Realistic AI Approach for Synthesizable Drug-like Molecules

arXiv: https://arxiv.org/abs/2601.18716 · HTML: https://mlsanity.com/paper/2601.18716/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 4 of its 52 references that are in the map.
- First posted on arXiv 26 Jan 2026.

## Builds on (most cited first, 4 of 4)

- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [Graph neural networks for materials science and chemistry](https://mlsanity.com/paper/2208.09481/) (2022)
- [Improved Variational Autoencoders for Text Modeling using Dilated Convolutions](https://mlsanity.com/paper/1702.08139/) (2017)
- [RGCVAE: Relational Graph Conditioned Variational Autoencoder for Molecule Design](https://mlsanity.com/paper/2305.11699/) (2023)

## Built on by (most cited first, 1 of 1)

- [A Systematic Evaluation of Molecule Generation Models for De Novo Drug Design: From Benchmarks to Practical Insights](https://mlsanity.com/paper/2609.10099/) (2026)

## Abstract (arXiv)

Alzheimer's disease (AD) is marked by the pathological accumulation of amyloid beta-42 (Abeta-42), contributing to synaptic dysfunction and neurodegeneration. While extracellular amyloid plaques are well-studied, increasing evidence highlights intracellular Abeta-42 as an early and toxic driver of disease progression. In this study, we present a novel, AI-assisted drug design approach to promote targeted degradation of Abeta-42 via the ubiquitin-proteasome system (UPS), using E3 ligase-directed molecular glues. We systematically evaluated the ternary complex formation potential of Abeta-42 with three E3 ligases: CRBN, VHL, and MDM2, through structure-based modeling, ADMET screening, and docking. We then developed a Ligase-Conditioned Junction Tree Variational Autoencoder (LC-JT-VAE) to generate ligase-specific small molecules, incorporating protein sequence embeddings and torsional angle-aware molecular graphs. Our results demonstrate that this generative model can produce chemically valid, novel, and target-specific molecular glues capable of facilitating Abeta-42 degradation. This integrated approach offers a promising framework for designing UPS-targeted therapies for neurodegenerative diseases.