CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

中文翻译：

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CARM1 抑制剂在体外和体内均能有效抑制乳腺癌


CARM1 属于蛋白精氨酸甲基转移酶 (PRMT) 家族，与癌症的进展密切相关，被视为癌症诊断和治疗的有希望的靶点。然而，特异性和有效的 CARM1 抑制剂的数量有限。我们在此发现了一种 CARM1 抑制剂 iCARM1，与已知的 CARM1 抑制剂 EZM2302 和 TP-064 相比，它对 CARM1 显示出更好的特异性和活性。与 CARM1 敲除类似，iCARM1 抑制乳腺癌细胞中致癌雌激素/ERα 靶基因的表达，同时激活 I 型干扰素 (IFN) 和 IFN 诱导基因 (ISG)。因此，iCARM1 在体外和体内均有效抑制乳腺癌细胞的生长。 iCARM1与内分泌治疗药物或依托泊苷的组合在抑制乳腺肿瘤的生长方面表现出协同作用。总之，iCARM1 靶向 CARM1 可有效抑制乳腺肿瘤生长，为临床治疗乳腺癌提供了一种有前景的治疗方法。