ZZW-115
ZZW-115is a potent NUPR1 inhibitor. ZZW-115 induces ferroptosis in a mitochondria-dependent manner. ZZW-115 induces ROS accumulation followed by a ferroptotic cell death, which could be prevented by ferrostatin-1 (Fer-1) and ROS-scavenging agents. In addition, ZZW-115-treatment increases the accumulation of hydroperoxided lipids in these cells. ZZW-115-induced mitochondrial morphological changes, compatible with the ferroptotic process, as well as mitochondrial network disorganization and strong mitochondrial metabolic dysfunction, which are rescued by both Fer-1 and N-acetylcysteine (NAC). Of note, the expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115.
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化学信息
| 名称 | ZZW-115 |
|---|---|
| Iupac 化学名称 | N,N-dimethyl-2-(4-(3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)propyl)piperazin-1-yl)ethan-1-amine |
| 同义词 | ZZW-115; ZZW 115; ZZW115; |
| 英文同义词 | ZZW-115; ZZW 115; ZZW115; |
| 分子式 | C24H31F3N4S |
| 分子量 | 464.59 |
| Smile | FC(C(C=C1N2CCCN3CCN(CCN(C)C)CC3)=CC=C1SC4=C2C=CC=C4)(F)F |
| InChiKey | HUDONDPCYIGAMQ-UHFFFAOYSA-N |
| InChi | InChI=1S/C24H31F3N4S/c1-28(2)12-13-30-16-14-29(15-17-30)10-5-11-31-20-6-3-4-7-22(20)32-23-9-8-19(18-21(23)31)24(25,26)27/h3-4,6-9,18H,5,10-17H2,1-2H3 |
| Cas号 | 801991-87-7 |
| 相关CAS号 |
订购信息
| 包装 | 价格 | 库存 | 纯度 | 备货期 |
|---|---|---|---|---|
| 大货 | 询价 | 询价 | 询价 |
| 外观性状 | 固体粉末 |
|---|---|
| 纯度 | 98% Min. |
| 存储 | 短期（几天到几周）为0-4摄氏度，长期（几个月）为-20摄氏度 |
| 可溶性 | 溶于DMSO |
| 处理方式 | |
| 运输条件 | 作为非危险化学品在环境温度下装运。这种产品在正常运输和海关工作期间可以稳定几周. |
| 海关编码 |
| Targets | |
|---|---|
| Mechanism | |
| Cell study | |
| Animal study | |
| Clinical study |
1: Rizzuti B, Lan W, Santofimia-Castaño P, Zhou Z, Velázquez-Campoy A, Abián O, Peng L, Neira JL, Xia Y, Iovanna JL. Design of Inhibitors of the Intrinsically Disordered Protein NUPR1: Balance between Drug Affinity and Target Function. Biomolecules. 2021 Oct 3;11(10):1453. doi: 10.3390/biom11101453. PMID: 34680086; PMCID: PMC8533202.
2: Huang C, Santofimia-Castaño P, Liu X, Xia Y, Peng L, Gotorbe C, Neira JL, Tang D, Pouyssegur J, Iovanna J. NUPR1 inhibitor ZZW-115 induces ferroptosis in a mitochondria-dependent manner. Cell Death Discov. 2021 Oct 1;7(1):269. doi: 10.1038/s41420-021-00662-2. PMID: 34599149; PMCID: PMC8486797.
3: Liu J, Song X, Kuang F, Zhang Q, Xie Y, Kang R, Kroemer G, Tang D. NUPR1 is a critical repressor of ferroptosis. Nat Commun. 2021 Jan 28;12(1):647. doi: 10.1038/s41467-021-20904-2. PMID: 33510144; PMCID: PMC7843652.
4: Santofimia-Castaño P, Lan W, Xia Y, Zhou Z, Huang C, Barea D, Cervello M, Giannitrapani L, Montalto G, Peng L, Iovanna J. Response to the Letter to the editor regarding "Targeting NUPR1 with the small compound ZZW-115 is an efficient strategy to treat hepatocellular carcinoma" by Jiong Lin. Cancer Lett. 2021 Mar 1;500:161-162. doi: 10.1016/j.canlet.2020.12.001. Epub 2020 Dec 5. PMID: 33290870.
5: Lin J. Letter to the editor regarding "Targeting NUPR1 with the small compound ZZW-115 is an efficient strategy to treat hepatocellular carcinoma". Cancer Lett. 2021 Feb 28;499:1. doi: 10.1016/j.canlet.2020.11.020. Epub 2020 Nov 21. PMID: 33232790.
6: Lan W, Santofimia-Castaño P, Swayden M, Xia Y, Zhou Z, Audebert S, Camoin L, Huang C, Peng L, Jiménez-Alesanco A, Velázquez-Campoy A, Abián O, Lomberk G, Urrutia R, Rizzuti B, Geli V, Soubeyran P, Neira JL, Iovanna J. ZZW-115-dependent inhibition of NUPR1 nuclear translocation sensitizes cancer cells to genotoxic agents. JCI Insight. 2020 Sep 17;5(18):e138117. doi: 10.1172/jci.insight.138117. PMID: 32780723; PMCID: PMC7526551.
7: Lan W, Santofimia-Castaño P, Xia Y, Zhou Z, Huang C, Fraunhoffer N, Barea D, Cervello M, Giannitrapani L, Montalto G, Peng L, Iovanna J. Targeting NUPR1 with the small compound ZZW-115 is an efficient strategy to treat hepatocellular carcinoma. Cancer Lett. 2020 Aug 28;486:8-17. doi: 10.1016/j.canlet.2020.04.024. Epub 2020 May 21. PMID: 32446862.
8: Santofimia-Castaño P, Xia Y, Peng L, Velázquez-Campoy A, Abián O, Lan W, Lomberk G, Urrutia R, Rizzuti B, Soubeyran P, Neira JL, Iovanna J. Targeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma. Cells. 2019 Nov 17;8(11):1453. doi: 10.3390/cells8111453. PMID: 31744261; PMCID: PMC6912534.
9: Santofimia-Castaño P, Xia Y, Lan W, Zhou Z, Huang C, Peng L, Soubeyran P, Velázquez-Campoy A, Abián O, Rizzuti B, Neira JL, Iovanna J. Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis. J Clin Invest. 2019 Mar 28;129(6):2500-2513. doi: 10.1172/JCI127223. PMID: 30920390; PMCID: PMC6546470.
