NL-103 is a novel dual-targeted inhibitor of histone deacetylases and hedgehog pathway, effectively overcomes vismodegib resistance conferred by Smo mutations. NL-103 comprises structural elements of Hh pathway inhibitor vismodegib, and histone deacetylase (HDAC) inhibitor vorinostat. NL-103 simultaneously and significantly inhibited both HDACs and Hh pathway. Importantly, NL-103 effectively overcame vismodegib resistance induced by Smoothened point mutations. Moreover, NL-103 significantly downregulated the expression of Gli2 which plays an important role in Hh pathway. NL-103 may be a promising compound for clinical development as a more effective Hh pathway inhibitor. References: Zhao J, Quan H, Xie C, Lou L. NL-103, a novel dual-targeted inhibitor of histone deacetylases and hedgehog pathway, effectively overcomes vismodegib resistance conferred by Smo mutations. Pharmacol Res Perspect. 2014 Jun;2(3):e00043. doi: 10.1002/prp2.43. Epub 2014 Apr 7. PubMed PMID: 25505589; PubMed Central PMCID: PMC4186412.

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CAS：1788896-33-2