CAS: 1443414-10-5; Trans-4-(7-Benzyl-4-Imino-5,6-Diphenyl-4,7-Dihydro-3H-Pyrrolo[2,3-D]Pyrimidin-3-yl)Cyclohexan-1-Ol

该化合物是一种该化合物是一种子核结构. 通过破坏PNC的完整性,Metarrestin在临床前型中表现出了强大的抗转移活动,抑制了肿瘤细胞迁移,入侵和传播.它的机制涉及干扰与癌症攻击性有关的笔录机,特别是通过抑制Pol I调解的RRNA合成. Metarrestin已经显示出在减少多种癌症类型的转移负担方面的效力,而没有给正常细胞带来严重的细胞毒性.它的定向行动和有利的药用皮肤特征使它成为进一步调查转移性疾病干预的有前途的候选者. 研究强调它作为治疗剂在分子一级阻碍癌症转移的潜力.

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    主要参考文献

    1. Frankowski KJ, Wang C, Patnaik S, Schoenen FJ, Southall N, Li D, Teper Y, Sun W, Kandela I, Hu D, Dextras C, Knotts Z, Bian Y, Norton J, Titus S, Lewandowska MA, Wen Y, Farley KI, Griner LM, Sultan J, Meng Z, Zhou M, Vilimas T, Powers AS, Kozlov S, Nagashima K, Quadri HS, Fang M, Long C, Khanolkar O, Chen W, Kang J, Huang H, Chow E, Goldberg E, Feldman C, Xi R, Kim HR, Sahagian G, Baserga SJ, Mazar A, Ferrer M, Zheng W, Shilatifard A, Aubé J, Rudloff U, Marugan JJ, Huang S. Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. Sci Transl Med. 2018 May 16;10(441):eaap8307. doi: 10.1126/scitranslmed.aap8307. 2. Vilimas T, Wang AQ, Patnaik S, Hughes EA, Singleton MD, Knotts Z, Li D, Frankowski K, Schlomer JJ, Guerin TM, Springer S, Drennan C, Dextras C, Wang C, Gilbert D, Southall N, Ferrer M, Huang S, Kozlov S, Marugan J, Xu X, Rudloff U. Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer. Cancer Chemother Pharmacol. 2018 Dec;82(6):1067-1080. doi: 10.1007/s00280-018-3699-0. Epub 2018 Oct 10.

    合成参考文献


    参考文献:10.1124/mol.119.115964
    摘要:Lee TD, Lee OW, Brimacombe KR, Chen L, Guha R, Lusvarghi S, Tebase BG, Klumpp-Thomas C, Robey RW, Ambudkar SV, Shen M, Gottesman MM, Hall MD. A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular Pharmacology. 2019 Nov;96(5):629–40. doi: 10.1124/mol.119.115964.
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