Drug Repositioning for Noonan and LEOPARD Syndromes by Integrating Transcriptomics With a Structure-Based Approach.

ABSTRACT: Noonan and LEOPARD syndromes (NS and LS) belong to a group of related disorders called RASopathies characterized by abnormalities of multiple organs and systems including hypertrophic cardiomyopathy and dysmorphic facial features. There are no approved drugs for these two rare diseases, but it is known that a missense mutation in PTPN11 genes is associated with approximately 50% and 70% of NS and LS cases, respectively. In this study, we implemented a hybrid computational drug repositioning framework by integrating transcriptomic and structure-based approaches to explore potential treatment options for NS and LS. Specifically, disease signatures were derived from the transcriptomic profiles of human induced pluripotent stem cells (iPSCs) from NS and LS patients and reverse correlated to dr

SUBMITTER: Zhu L 

PROVIDER: S-EPMC7333460 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature