用于治疗乳腺癌的双特异性酪蛋白激酶1δ/1ε（CK1δ/ε）抑制剂的研发。
Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer.
作者信息
Monastyrskyi Andrii, Nilchan Napon, Quereda Victor, Noguchi Yoshihiko, Ruiz Claudia, Grant Wayne, Cameron Michael, Duckett Derek, Roush William
机构信息
Department of Chemistry, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, United States.
Department of Molecular Medicine, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, United States.
出版信息
Bioorg Med Chem. 2018 Feb 1;26(3):590-602. doi: 10.1016/j.bmc.2017.12.020. Epub 2017 Dec 15.
Abstract
Casein kinase 1δ/ε have been identified as promising therapeutic target for oncology application, including breast and brain cancer. Here, we described our continued efforts in optimization of a lead series of purine scaffold inhibitors that led to identification of two new CK1δ/ε inhibitors 17 and 28 displaying low nanomolar values in antiproliferative assays against the human MDA-MB-231 triple negative breast cancer cell line and have physical, in vitro and in vivo pharmacokinetic properties suitable for use in proof of principle animal xenograft studies against human cancers.
摘要
酪蛋白激酶1δ/ε已被确定为肿瘤学应用（包括乳腺癌和脑癌）中很有前景的治疗靶点。在此，我们描述了我们在优化嘌呤骨架抑制剂先导系列方面的持续努力，这导致鉴定出两种新的CK1δ/ε抑制剂17和28，它们在针对人MDA-MB-231三阴性乳腺癌细胞系的抗增殖试验中显示出低纳摩尔值，并且具有适合用于针对人类癌症的原理验证动物异种移植研究的物理、体外和体内药代动力学特性。
相似文献
1
Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer.用于治疗乳腺癌的双特异性酪蛋白激酶1δ/1ε（CK1δ/ε）抑制剂的研发。
Bioorg Med Chem. 2018 Feb 1;26(3):590-602. doi: 10.1016/j.bmc.2017.12.020. Epub 2017 Dec 15.
2
Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties.开发具有高选择性的酪蛋白激酶 1δ/1ε（CK1δ/ε）抑制剂，具有强大的抗增殖特性。
Bioorg Med Chem Lett. 2013 Aug 1;23(15):4374-80. doi: 10.1016/j.bmcl.2013.05.075. Epub 2013 May 31.
3
N-(1H-Pyrazol-3-yl)quinazolin-4-amines as a novel class of casein kinase 1δ/ε inhibitors: Synthesis, biological evaluation and molecular modeling studies.新型酪蛋白激酶1δ/ε抑制剂N-(1H-吡唑-3-基)喹唑啉-4-胺：合成、生物学评价及分子模拟研究
Bioorg Med Chem Lett. 2017 Jun 15;27(12):2663-2667. doi: 10.1016/j.bmcl.2017.04.080. Epub 2017 Apr 27.
4
IC261 suppresses progression of hepatocellular carcinoma in a casein kinase 1 δ/ε independent manner.IC261 通过不依赖于酪蛋白激酶 1 δ/ε 的方式抑制肝细胞癌的进展。
Biochem Biophys Res Commun. 2020 Mar 12;523(3):809-815. doi: 10.1016/j.bbrc.2019.12.105. Epub 2020 Jan 15.
5
Therapeutic targeting of casein kinase 1δ in breast cancer.乳腺癌中酪蛋白激酶1δ的治疗靶点
Sci Transl Med. 2015 Dec 16;7(318):318ra202. doi: 10.1126/scitranslmed.aac8773.
6
Discovery of Inhibitor of Wnt Production 2 (IWP-2) and Related Compounds As Selective ATP-Competitive Inhibitors of Casein Kinase 1 (CK1) δ/ε.Wnt 产生抑制剂 2（IWP-2）及相关化合物的发现作为酪蛋白激酶 1（CK1）δ/ε 的选择性 ATP 竞争性抑制剂。
J Med Chem. 2018 May 10;61(9):4087-4102. doi: 10.1021/acs.jmedchem.8b00095. Epub 2018 May 1.
7
Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε.阻断生物钟调节激酶 CK1δ/ε后，αENaC 的表达和 ENaC 活性受到抑制。
Am J Physiol Renal Physiol. 2012 Oct;303(7):F918-27. doi: 10.1152/ajprenal.00678.2011. Epub 2012 Jul 25.
8
Casein kinase 1 is a therapeutic target in chronic lymphocytic leukemia.酪蛋白激酶 1 是慢性淋巴细胞白血病的治疗靶点。
Blood. 2018 Mar 15;131(11):1206-1218. doi: 10.1182/blood-2017-05-786947. Epub 2018 Jan 9.
9
Casein kinase 1δ activity: a key element in the zebrafish circadian timing system.酪蛋白激酶 1δ 活性：斑马鱼生物钟计时系统的关键要素。
PLoS One. 2013;8(1):e54189. doi: 10.1371/journal.pone.0054189. Epub 2013 Jan 21.
10
Structural basis for the potent and selective inhibition of casein kinase 1 epsilon.结构基础强效和选择性抑制酪蛋白激酶 1 epsilon。
J Med Chem. 2012 Nov 26;55(22):10307-11. doi: 10.1021/jm301336n. Epub 2012 Nov 9.
引用本文的文献
1
Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.昼夜节律失调与肿瘤发生、肿瘤代谢及肿瘤免疫反应之间的相互作用
Aging Dis. 2024 Jul 2. doi: 10.14336/AD.2024.0533.
2
The CDK12 inhibitor SR-4835 functions as a molecular glue that promotes cyclin K degradation in melanoma.细胞周期蛋白依赖性激酶12（CDK12）抑制剂SR-4835作为一种分子胶，可促进黑色素瘤中细胞周期蛋白K的降解。
Cell Death Discov. 2023 Dec 16;9(1):459. doi: 10.1038/s41420-023-01754-x.
3
Design principles for cyclin K molecular glue degraders.周期蛋白 K 分子胶降解剂的设计原则。
Nat Chem Biol. 2024 Jan;20(1):93-102. doi: 10.1038/s41589-023-01409-z. Epub 2023 Sep 7.
4
"Dual Anta-Inhibitors" of the A Adenosine Receptor and Casein Kinase CK1delta: Synthesis, Biological Evaluation, and Molecular Modeling Studies.A腺苷受体与酪蛋白激酶CK1δ的“双拮抗剂”：合成、生物学评价及分子模拟研究
Pharmaceuticals (Basel). 2023 Jan 23;16(2):167. doi: 10.3390/ph16020167.
5
Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1ε vs Casein Kinase 1δ.基于结构的酪蛋白激酶 1ε 与酪蛋白激酶 1δ 同工型选择性抑制剂的开发。
J Med Chem. 2023 Jun 8;66(11):7162-7178. doi: 10.1021/acs.jmedchem.2c01180. Epub 2023 May 19.
6
Roles of circadian clocks in cancer pathogenesis and treatment.昼夜节律钟在癌症发病机制和治疗中的作用。
Exp Mol Med. 2021 Oct;53(10):1529-1538. doi: 10.1038/s12276-021-00681-0. Epub 2021 Oct 7.
7
Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives.直接靶向 Wnt 信号通路中的 β-连环蛋白：当前进展和展望。
Med Res Rev. 2021 Jul;41(4):2109-2129. doi: 10.1002/med.21787. Epub 2021 Jan 21.
8
Targeting Casein Kinase 1 Delta Sensitizes Pancreatic and Bladder Cancer Cells to Gemcitabine Treatment by Upregulating Deoxycytidine Kinase.靶向酪蛋白激酶 1 德尔塔通过上调脱氧胞苷激酶使胰腺和膀胱癌对吉西他滨治疗敏感。
Mol Cancer Ther. 2020 Aug;19(8):1623-1635. doi: 10.1158/1535-7163.MCT-19-0997. Epub 2020 May 19.
9
Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents.芳基氨基脲衍生物作为潜在抗癌剂的生物学评价
Pharmaceuticals (Basel). 2019 Nov 17;12(4):169. doi: 10.3390/ph12040169.
10
The nucleolus, an ally, and an enemy of cancer cells.核仁，癌细胞的一个盟友和一个敌人。
Histochem Cell Biol. 2018 Dec;150(6):607-629. doi: 10.1007/s00418-018-1706-5. Epub 2018 Aug 13.
本文引用的文献
1
Therapeutic targeting of casein kinase 1δ in breast cancer.乳腺癌中酪蛋白激酶1δ的治疗靶点
Sci Transl Med. 2015 Dec 16;7(318):318ra202. doi: 10.1126/scitranslmed.aac8773.
2
Bioactivation potential of thiophene-containing drugs.含噻吩药物的生物活化潜力。
Chem Res Toxicol. 2014 Aug 18;27(8):1344-58. doi: 10.1021/tx500134g. Epub 2014 Jul 21.
3
The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis.CK1家族：对细胞应激反应的贡献及其在肿瘤发生中的作用。
Front Oncol. 2014 May 19;4:96. doi: 10.3389/fonc.2014.00096. eCollection 2014.
4
One-pot synthesis and applications of N-heteroaryl iodonium salts.一锅法合成 N-杂芳基碘𬭩盐及其应用。
ChemistryOpen. 2014 Feb;3(1):19-22. doi: 10.1002/open.201300042. Epub 2014 Jan 23.
5
Wnt signaling in triple negative breast cancer is associated with metastasis.Wnt 信号通路在三阴性乳腺癌中与转移相关。
BMC Cancer. 2013 Nov 10;13:537. doi: 10.1186/1471-2407-13-537.
6
Structure-guided inhibitor design expands the scope of analog-sensitive kinase technology.结构导向抑制剂设计拓展了模拟敏感激酶技术的应用范围。
ACS Chem Biol. 2013 Sep 20;8(9):1931-8. doi: 10.1021/cb400376p. Epub 2013 Jul 23.
7
Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties.开发具有高选择性的酪蛋白激酶 1δ/1ε（CK1δ/ε）抑制剂，具有强大的抗增殖特性。
Bioorg Med Chem Lett. 2013 Aug 1;23(15):4374-80. doi: 10.1016/j.bmcl.2013.05.075. Epub 2013 May 31.
8
β-Catenin signaling is a critical event in ErbB2-mediated mammary tumor progression.β-连环蛋白信号转导是 ErbB2 介导的乳腺肿瘤进展中的关键事件。
Cancer Res. 2013 Jul 15;73(14):4474-87. doi: 10.1158/0008-5472.CAN-12-3925. Epub 2013 May 29.
9
Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments.蛋白质和配体准备：参数、方案以及对虚拟筛选富集的影响。
J Comput Aided Mol Des. 2013 Mar;27(3):221-34. doi: 10.1007/s10822-013-9644-8. Epub 2013 Apr 12.
10
The planar cell polarity pathway drives pathogenesis of chronic lymphocytic leukemia by the regulation of B-lymphocyte migration.平面细胞极性通路通过调节 B 淋巴细胞迁移来驱动慢性淋巴细胞白血病的发病机制。
Cancer Res. 2013 Mar 1;73(5):1491-501. doi: 10.1158/0008-5472.CAN-12-1752. Epub 2013 Jan 21.
Zotero 插件