Machine learning-based phenotypic screening for postmitotic growth inducers uncover vitamin D3 metabolites as small molecule ribosome agonists.

ABSTRACT:

Objectives

To restore tissue growth without increasing the risk for cancer during aging, there is a need to identify small molecule drugs that can increase cell growth without increasing cell proliferation. While there have been numerous high-throughput drug screens for cell proliferation, there have been few screens for post-mitotic anabolic growth.

Materials and methods

A machine learning (ML)-based phenotypic screening strategy was used to discover metabolites that boost muscle growth. Western blot, qRT-PCR and immunofluorescence staining were used to evaluate myotube hypertrophy/maturation or protein synthesis. Mass spectrometry (MS)-based thermal proteome profiling-temperature range (TPP-TR) technology was used to identify the protein targets that bind the metabolites.

SUBMITTER: Jiang Z 

PROVIDER: S-EPMC9136510 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature