The nitrogen mustards are powerful cytotoxic and lymphoablative agents and have been used for more than 60 years. They are employed in the treatment of cancers, sarcomas, and hematologic malignancies. Cyclophosphamide, the most versatile of the nitrogen mustards, also has a place in stem cell transplantation and the therapy of autoimmune diseases. Adverse effects caused by the nitrogen mustards on the central nervous system, kidney, heart, bladder, and gonads remain important issues. Advances in analytical techniques have facilitated the investigation of the pharmacokinetics of the nitrogen mustards, especially the oxazaphosphorines, which are prodrugs requiring metabolic activation. Enzymes involved in the metabolism of cyclophosphamide and ifosfamide are very polymorphic, but a greater understanding of the pharmacogenomic influences on their activity has not yet translated into a personalized medicine approach. In addition to damaging DNA, the nitrogen mustards can act through other mechanisms, such as antiangiogenesis and immunomodulation. The immunomodulatory properties of cyclophosphamide are an area of current exploration. In particular, cyclophosphamide decreases the number and activity of regulatory T cells, and the interaction between cyclophosphamide and the intestinal microbiome is now recognized as an important factor. New derivatives of the nitrogen mustards continue to be assessed. Oxazaphosphorine analogs have been synthesized in attempts to both improve efficacy and reduce toxicity, with varying degrees of success. Combinations of the nitrogen mustards with monoclonal antibodies and small-molecule targeted agents are being evaluated.

中文翻译：

---

氮芥末

氮芥是强大的细胞毒剂和清淋巴剂，已经使用了 60 多年。它们用于治疗癌症、肉瘤和血液系统恶性肿瘤。环磷酰胺是最通用的氮芥，在干细胞移植和自身免疫性疾病的治疗中也占有一席之地。氮芥对中枢神经系统、肾脏、心脏、膀胱和性腺造成的不利影响仍然是重要问题。分析技术的进步促进了对氮芥的药代动力学的研究，尤其是作为需要代谢活化的前药的氧氮杂膦。参与环磷酰胺和异环磷酰胺代谢的酶是非常多态的，但对药物基因组对其活动影响的更深入了解尚未转化为个性化医疗方法。除了破坏 DNA 之外，氮芥还可以通过其他机制发挥作用，例如抗血管生成和免疫调节。环磷酰胺的免疫调节特性是当前探索的一个领域。特别是环磷酰胺降低了调节性 T 细胞的数量和活性，环磷酰胺与肠道微生物群之间的相互作用现在被认为是一个重要因素。继续评估氮芥的新衍生物。已合成恶氮膦类似物以尝试提高功效和降低毒性，并取得了不同程度的成功。