Mirin is an inhibitor of Mre11-Rad50-Nbs1 (MRN) complex (IC50=12μM), which can inhibit the activity of MRE11-related exonuclease, and can inhibit the activation of MRN-dependent ATM[1]. It is commonly used in the study of cancers related to DNA repair mechanisms[1].
Mirin (100µM, 24 hours) significantly enhanced the sensitivity of human papillomavirus (HPV) to N-methylpyrrole-imidazole hairpin polyamide (PA25)[2]. Mirin (50μM, 24h) significantly enhanced DNA double-strand breaks and promoted cell apoptosis in esophageal squamous cell carcinoma (ESCC) cells treated with NU7441 and ionizing radiation treatment[3].
Mirin (50mg/kg/day, 9 days, intratumoral injection) efficiently restrains tumor growth in Neuroblastoma mouse model by inducing DNA damage response (DDR) and apoptosis[4]. Mirin (50mg/kg, 72 hours, i.p.) significantly increased tubular damage and serum markers of acute kidney injury (AKI) (creatinine and neutrophil gelatinase-associated lipocalin) in cisplatin-induced nephrotoxic AKI mouse model[5].
References:
[1] Dupré A, Boyer-Chatenet L, Sattler RM, et al. A forward chemical genetic screen reveals an inhibitor of the Mre11–Rad50–Nbs1 complex. Nature chemical biology. 2008 Feb;4(2):119-25.
[2] Edwards TG, Vidmar TJ, Koeller K, et al. DNA damage repair genes controlling human papillomavirus (HPV) episome levels under conditions of stability and extreme instability. PloS one. 2013 Oct 2;8(10):e75406.
[3] Wang G, Guo S, Zhang W, et al. A comprehensive analysis of alterations in DNA damage repair pathways reveals a potential way to enhance the radio-sensitivity of esophageal squamous cell cancer. Frontiers in oncology. 2020 Oct 16;10:575711.
[4] Petroni M, Sardina F, Infante P, et al. MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors. Cell death & disease. 2018 Aug 30;9(9):895.
[5] Hama T, Nagesh PK, Chowdhury P, et al. DNA damage is overcome by TRIP13 overexpression during cisplatin nephrotoxicity. JCI insight. 2021 Nov 11;6(22).
Mirin是一种Mre11-Rad50-Nbs1（MRN）复合物抑制剂（IC50=12μM），能够抑制Mre11相关的外切酶活性，Mirin可抑制MRN依赖的ATM的激活[1]。通常用于与DNA修复机制相关的癌症的研究[1]。
Mirin（100µM，24小时）显著增强了人乳头瘤病毒（HPV）对N-甲基吡咯-咪唑发夹聚酰胺（PA25）的敏感性[2]。在NU7441和电离辐射处理的食管鳞状细胞癌细胞（ESCC）中，Mirin（50μM，24小时）显著增强DNA双链的断裂，显著促进细胞凋亡[3]。
Mirin（50 mg/kg/d，9天，瘤内注射）在神经母细胞瘤小鼠模型中通过诱导DNA损伤反应（DDR）和细胞凋亡有效抑制肿瘤生长[4]。在顺铂诱导的肾毒性的急性肾损伤（AKI）小鼠模型中，Mirin（50mg/kg，72小时，腹腔注射）显著增加了肾小管损伤和AKI血清标志物（肌酐和中性粒细胞明胶酶相关脂质运载蛋白）[5]。