Pan-HDAC inhibitors exhibit significant inhibitory activity against multiple myeloma, however, their clinical applications have been hampered by substantial toxic side effects. In contrast, selective HDAC6 inhibitors have demonstrated effectiveness in treating multiple myeloma. Compounds belonging to the class of 1H-benzo[d]imidazole hydroxamic acids have been identified as novel HDAC6 inhibitors, with the benzimidazole group serving as a specific linker for these inhibitors. Notably, compound 30 has exhibited outstanding HDAC6 inhibitory activity (IC₅₀ = 4.63 nM) and superior antiproliferative effects against human multiple myeloma cells, specifically RPMI-8226. Moreover, it has been shown to induce cell cycle arrest in the G2 phase and promote apoptosis through the mitochondrial pathway. In a myeloma RPMI-8226 xenograft model, compound 30 has demonstrated significant in vivo antitumor efficacy (T/C = 34.8%) when administered as a standalone drug, with no observable cytotoxicity. These findings underscore the immense potential of compound 30 as a promising therapeutic agent for the treatment of multiple myeloma.

Pan-HDAC抑制剂对多发性骨髓瘤表现出显着的抑制活性，然而，其临床应用却因严重的毒副作用而受到阻碍。相比之下，选择性 HDAC6 抑制剂已被证明可有效治疗多发性骨髓瘤。属于 1 H-苯并[ d ]咪唑异羟肟酸类的化合物已被鉴定为新型 HDAC6 抑制剂，其中苯并咪唑基团充当这些抑制剂的特定连接体。值得注意的是，化合物30 对人多发性骨髓瘤细胞（特别是 RPMI-8226）表现出出色的 HDAC6 抑制活性（IC _{50 = 4.63 nM）和卓越的抗增殖作用。}此外，它已被证明可以诱导细胞周期停滞在 G2 期，并通过线粒体途径促进细胞凋亡。在骨髓瘤 RPMI-8226 异种移植模型中，化合物30作为独立药物给药时表现出显着的体内抗肿瘤功效 (T/C = 34.8%)，且没有可观察到的细胞毒性。这些发现强调了化合物30作为治疗多发性骨髓瘤的有前途的治疗剂的巨大潜力。