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.

Gαi2-IN-1 (Compound 14) is an inhibitor of Gαi2 that significantly suppresses cancer cell migration induced by chemotherapeutic agents such as Vorinostat and Docetaxel. It is applicable in research involving various cancers, including prostate, breast, and ovarian cancers.

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].