biostudies-literatureJiang ZWhole People Nutrition Research FundNational Key R&D Program of ChinaHoward Hughes Medical InstituteStrategic Priority Research Program of the CASState Key Laboratory of Stem Cell and Reproductive BiologyNational Natural Science Foundation of ChinaKey Research Program of the CASCAS Project for Young Scientists in Basic ResearchBill and Melinda Gates Foundatione13214https://www.ebi.ac.uk/biostudies/studies/S-EPMC9136510biostudies-literatureUnknown55(5)<h4>Objectives</h4>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.<h4>Materials and methods</h4>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. Cell proliferationMachine learning-based phenotypic screening for postmitotic growth inducers uncover vitamin D3 metabolites as small molecule ribosome agonists.PMC91365102021YFE01118002018YFC10041022019YFA080170181900782YSBR-0122018YFE0201100CNSNNSRG2021-12991957202XDA16010109KJZD-SW-L04Jiang ZZheng ZYao ZMa SGuang LLi CCao WShyh-Chang NChen YZhang LYu KfalseMachine learning-based phenotypic screening for postmitotic growth inducers uncover vitamin D3 metabolites as small molecule ribosome agonists.<h4>Objectives</h4>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.<h4>Materials and methods</h4>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. 2022-01-01T00:00:00Z2022 May2025-06-01T00:13:02.544Z2025-02-19T04:57:07.066ZS-EPMC91365103541155610.1111/cpr.13214