Abstract

Analysis of the literature data reveals that while inhibition of cancer-related carbonic anhydrase IX and XII isoforms continues to be an important enrichment factor for designing anticancer agent development libraries, exclusive reliance on the in vitro inhibition of these two recombinant isozymes in nominating candidate compounds for evaluation of their effects on cancer cells may lead not only to identifying numerous compounds devoid of the desired cellular efficacy but also to overlooking many promising candidates which may not display the best potency in biochemical inhibition assay. However, SLC-0111, now in phase Ib/II clinical trials, was developed based on the excellent agreement between the in vitro, in vivo and more recently, in-patient data.

摘要

对文献数据的分析表明，尽管抑制癌症相关的碳酸酐酶IX和XII同工型仍然是设计抗癌药开发文库的重要富集因素，但在提名候选化合物时完全依赖于体外抑制这两种重组同工酶。评估它们对癌细胞的作用可能不仅会导致鉴定出许多缺乏所需细胞功效的化合物，而且会导致忽略许多有前途的候选物，而这些候选物可能在生化抑制试验中未显示出最佳的效力。但是，SLC-0111（目前处于Ib / II期临床试验）是根据体外，体内以及最近的住院数据之间的出色协议开发的。