Department of Molecular Target Medicine, Aichi Medical UniversityNagakuteJapan.
Department of Pathophysiology, Poznan University of Medical SciencesPoznanPoland.
Oncol Res. 2020 Dec 10;28(5):541-550. doi: 10.3727/096504020X15929100013698. Epub 2020 Jun 23.
There have been great advances in the therapy of cancer and leukemia. However, there are still many neoplastic diseases that are difficult to treat. For example, it is often difficult to find effective therapies for aggressive cancer and leukemia. An NF-κB inhibitor named dehydroxymethylepoxyquinomicin (DHMEQ) was discovered in 2000. This compound was designed based on the structure of epoxyquinomicin isolated from a microorganism. It was shown to be a specific inhibitor that directly binds to and inactivates NF-κB components. Until now, DHMEQ has been used by many scientists in the world to suppress animal models of cancer and inflammation. Especially, it was shown to suppress difficult cancer models, such as hormone-insensitive breast cancer and prostate cancer, cholangiocarcinoma, and multiple myeloma. No toxicity has been reported so far. DHMEQ was administered via the intraperitoneal (IP) route in most of the animal experiments because of its simplicity. In the course of developmental studies, it was found that IP administration never increased the blood concentration of DHMEQ because of the instability of DHMEQ in the blood. It is suggested that inflammatory cells in the peritoneal cavity would be important for cancer progression, and that IP administration, itself, is important for the effectiveness and safety of DHMEQ. In the present review, we describe mechanism of action, its in vivo anticancer activity, and future clinical use of DHMEQ IP therapy.
在癌症和白血病的治疗方面已经取得了重大进展。然而，仍有许多肿瘤疾病难以治疗。例如，对于侵袭性癌症和白血病，通常很难找到有效的治疗方法。一种名为去羟甲基环氧青蒿素（DHMEQ）的 NF-κB 抑制剂于 2000 年被发现。这种化合物是根据从微生物中分离出的环氧青蒿素的结构设计的，它被证明是一种直接与 NF-κB 成分结合并使其失活的特异性抑制剂。到目前为止，DHMEQ 已被世界上许多科学家用于抑制癌症和炎症的动物模型。特别是，它被证明可以抑制难以治疗的癌症模型，如激素不敏感的乳腺癌和前列腺癌、胆管癌和多发性骨髓瘤。到目前为止，还没有报道毒性。由于其简单性，DHMEQ 在大多数动物实验中通过腹腔内（IP）途径给药。在开发研究过程中，人们发现由于 DHMEQ 在血液中的不稳定性，IP 给药从未增加 DHMEQ 的血液浓度。这表明腹腔内的炎症细胞对于癌症的进展很重要，而 IP 给药本身对于 DHMEQ 的有效性和安全性很重要。在本综述中，我们描述了 DHMEQ 的作用机制、体内抗癌活性以及 IP 治疗的未来临床应用。
