Hutchinson–Gilford Progeria Syndrome (HGPS) is a rare and autosomal recessive genetic disorder resulting in accelerated aging in affected patients. In this condition, a single point mutation promotes the usage of an alternative splice site in exon 11 of the LMNA gene. This mutation results in a truncated protein called progerin, which is responsible for the symptoms of the disease. Previous studies have demonstrated that small molecules are able to change splicing patterns. However, there is not enough scientific report for progerin RNA and small molecule binders. In this regard, we aim to understand and to ameliorate a binding assay in order to detect small molecule binders to our target RNA hairpin structure. To reach our aim, 50 compounds from RNA binding small molecule libraries were filtered by molecular docking in silico. We also developed Microscale thermophoresis (MST) assay that shows that compounds could bind to target RNA hairpin. This method could detect possible binding interaction of filtered compounds with LMNA exon 11 cryptic splice site. The results give the first insights into the relationship between compounds and the target RNA hairpin. Further assays are required to understand splicing modulation of selected compounds binding to the target RNA hairpin. Yet this work would provide detection of small molecule binders from different libraries, besides developing a binding assay could provide detection of small molecule binders to other RNA structures in other splicing-linked diseases.