vorinostat

Vorinostat (SAHA) is a pan-histone deacetylase (HDAC) inhibitor (IC50=10 nM) with inhibitory activity against HDAC1 2 3 6 7 11. Vorinostat has antitumor activity, induces cell differentiation, blocks the cell cycle and induces apoptosis.

SAHA chloroalkane T1 is a novel compound formed by combining Vorinostat (SAHA) with a chloroalkane capture tag, referred to as T1. This innovative approach involves tethering the SAHA molecule with the T1 tag, resulting in the formation of SAHA chloroalkane T1.

POI ligand 1 serves as a template for the non-selective HDAC inhibitor Vorinostat. It functions as a target protein ligand (PROTAC target protein ligand) in the creation of PROTAC HDAC degraders with anti-tumor properties. Additionally, POI ligand 1 is utilized in the synthesis of FF2049.

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.

BPR1J-340 is a potent and selective FLT3 inhibitor with potential anticancer activity. BPR1J-340 was identified as a novel potent FLT3 inhibitor by biochemical kinase activity (IC50 approximately 25 nM) and cellular proliferation (GC50 approximately 5 nM) assays. BPR1J-340 inhibited the phosphorylation of FLT3 and STAT5 and triggered apoptosis in FLT3-ITD(+) AML cells. The pharmacokinetic parameters of BPR1J-340 in rats were determined. BPR1J-340 also demonstrated pronounced tumor growth inhibition and regression in FLT3-ITD(+) AML murine xenograft models. The combination treatment of the HDAC inhibitor vorinostat (SAHA) with BPR1J-340 synergistically induced apoptosis via Mcl-1 down-regulation in MOLM-13 AML cells, indicating that the combination of selective FLT3 kinase inhibitors and HDAC inhibitors could exhibit clinical benefit in AML therapy.

HL23 is a histone deacetylase (HDAC) inhibitor that effectively targets hepatocellular carcinoma (HCC). It promotes acetylation at the TXNIP promoter and increases TXNIP expression, modulating potassium channel activity and inducing TXNIP-dependent potassium deficiency. Additionally, HL23 impedes HCC progression and spread, demonstrating greater potency when combined with Sorafenib than the Sorafenib and Vorinostat duo [1].