Mitogen-activated protein kinase (MAPK) pathways that direct cellular responses are involved in various biological processes; the RAS-RAF-MEK-ERK pathway is one of the most important MAPK pathways. It is frequently activated in human malignant tumors such as melanomas, thyroid tumors and colorectal carcinomas. Therefore, targeting this pathway has been considered an attractive strategy for new anticancer drugs. In particular, MEK is a promising target because it is a kinase that directly phosphorylates ERK. We performed a screening to discover new MEK inhibitors, and found a guanine derivative produced by Streptomyces sp. MK63-43F2. This guanine derivative was identified to be 2-amino-4-methoxy-5-cyanopyrrolo[2,3-d]pyrimidine (1) through spectroscopic analysis. Compound 1 inhibited MEK1 kinase activity in an ATP-dependent manner and suppressed the phosphorylation of ERK in cancer cells and cell proliferation. Therefore, 1 might be a potent lead compound for new MEK inhibitors.The Journal of Antibiotics advance online publication, 6 September 2017; doi:10.1038/ja.2017.100.

中文翻译：

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鸟嘌呤衍生物作为链霉菌属的一种新的MEK抑制剂。MK63-43F2。

指导细胞反应的丝裂原活化蛋白激酶（MAPK）途径涉及各种生物学过程。RAS-RAF-MEK-ERK途径是最重要的MAPK途径之一。它经常在人类恶性肿瘤如黑色素瘤，甲状腺肿瘤和结直肠癌中被激活。因此，靶向该途径被认为是新的抗癌药物的有吸引力的策略。特别地，MEK是有前途的靶标，因为它是直接磷酸化ERK的激酶。我们进行了筛选，以发现新的MEK抑制剂，并发现了链霉菌sp。产生的鸟嘌呤衍生物。MK63-43F2。通过光谱分析鉴定该鸟嘌呤衍生物为2-氨基-4-甲氧基-5-氰基吡咯并[2，3-d]嘧啶（1）。化合物1以ATP依赖性方式抑制MEK1激酶活性，并抑制癌细胞中ERK的磷酸化和细胞增殖。因此，1可能是新型MEK抑制剂的有效先导化合物。《抗生素杂志》提前在线发布，2017年9月6日; doi：10.1038 / ja.2017.100。