Optimizing blood-brain barrier permeability in KRAS inhibitors: A structure-constrained molecular generation approach.

ABSTRACT: Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically ai

SUBMITTER: Sheng X 

PROVIDER: S-EPMC12398849 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature