Title:A Quinquennial Review of Potent LSD1 Inhibitors Explored for the
Treatment of Different Cancers, with Special Focus on SAR Studies
Volume: 31
Issue: 2
关键词:
癌症，赖氨酸特异性去甲基化酶1，LSD1抑制剂，抗LSD1，抗癌活性，癌细胞系，结构活性关系（SAR），设计，合成，天然产物。
摘要: Cancer bears a significant share of global mortality. The enzyme Lysine Specific
Demethylase 1 (LSD1, also known as KDM1A), since its discovery in 2004, has
captured the attention of cancer researchers due to its overexpression in several cancers
like acute myeloid leukaemia (AML), solid tumours, etc. The Lysine Specific Demethylase
(LSD1) downregulation is reported to have an effect on cancer proliferation, migration,
and invasion. Therefore, research to discover safer and more potent LSD1 inhibitors
can pave the way for the development of better cancer therapeutics. These efforts have resulted
in the synthesis of many types of derivatives containing diverse structural nuclei.
The present manuscript describes the role of Lysine Specific Demethylase 1 (LSD1) in
carcinogenesis, reviews the LSD1 inhibitors explored in the past five years and discusses
their comprehensive structural activity characteristics apart from the thorough description
of LSD1. Besides, the potential challenges, opportunities, and future perspectives in
the development of LSD1 inhibitors are also discussed. The review suggests that tranylcypromine
derivatives are the most promising potent LSD1 inhibitors, followed by triazole
and pyrimidine derivatives with IC50 values in the nanomolar and sub-micromolar
range. A number of potent LSD1 inhibitors derived from natural sources like resveratrol,
protoberberine alkaloids, curcumin, etc. are also discussed. The structural-activity relationships
discussed in the manuscript can be exploited to design potent and relatively
safer LSD1 inhibitors as anticancer agents.
