Machine-Learning Guided Discovery of Bioactive Inhibitors of PD1-PDL1 Interaction.

ABSTRACT: The selective activation of the innate immune system through blockade of immune checkpoint PD1-PDL1 interaction has proven effective against a variety of cancers. In contrast to six antibody therapies approved and several under clinical investigation, the development of small-molecule PD1-PDL1 inhibitors is still in its infancy with no such drugs approved yet. Nevertheless, a promising series of small molecules inducing PDL1 dimerization has revealed important spatio-chemical features required for effective PD1-PDL1 inhibition through PDL1 sequestration. In the present study, we utilized these features for developing machine-learning (ML) classifiers by fitting Random Forest models to six 2D fingerprint descriptors. A focused database of ~16 K bioactive molecules, including approved and ex

SUBMITTER: Patil SP 

PROVIDER: S-EPMC9145945 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature