vorinostat

Vorinostat (SAHA) 是一种泛的组蛋白脱乙酰酶 (HDAC) 抑制剂 (IC50=10 nM)，对 HDAC1 2 3 6 7 11 均有抑制活性。 Vorinostat 具有抗肿瘤活性，可以诱导细胞分化，阻滞细胞周期，诱导细胞凋亡。

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是非选择性HDAC抑制剂Vorinostat的基础。它作为靶蛋白配体 (PROTAC 靶蛋白配体) 被用于开发具抗肿瘤活性的PROTAC HDAC降解剂。此外，POI ligand 1还用于合成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是一种HDAC抑制剂，对抗HCC具有活性。通过增强TXNIP启动子乙酰化，此化合物上调TXNIP表达，进而介导钾通道活性并触发TXNIP依赖性钾剥夺，抑制HCC的进展和转移。HL23与Sorafenib联合应用时显示出协同作用，并且其效力超过Sorafenib与Vorinostat的联用。