Nutlin-3a (BioDeep_00000789161)
代谢物信息卡片
Nutlin-3a
化学式: C30H30Cl2N4O4 (580.1644)
中文名称: 4-[[(4S,5R)-4,5-双(4-氯苯基)-4,5-二氢-2-[4-甲氧基-2-(1-甲基乙氧基)苯基]-1H-咪唑-1-YL]羰基]-2-哌嗪酮
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl
InChI: InChI=1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)/t27-,28+/m0/s1
描述信息
C274 - Antineoplastic Agent > C129839 - Apoptotic Pathway-targeting Antineoplastic Agent > C162996 - MDM2 Inhibitor
Nutlin-3a (Rebemadlin), an active enantiomer of Nutlin-3, is a potent murine double minute (MDM2) inhibitor (IC50=90 nM). Nutlin-3a inhibits MDM2-p53?interactions and stabilizes the p53 protein, and induces cell autophagy and apoptosis. Nutlin-3a has the potential for the study of TP53?wild-type ovarian carcinomas[1][2].
同义名列表
2 个代谢物同义名
数据库引用编号
5 个数据库交叉引用编号
- ChEBI: CHEBI:95096
- PubChem: 11433190
- ChEMBL: CHEMBL191334
- CAS: 675576-98-4
- medchemexpress: HY-10029
分类词条
相关代谢途径
Reactome(0)
BioCyc(0)
PlantCyc(0)
代谢反应
0 个相关的代谢反应过程信息。
Reactome(0)
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(0)
PharmGKB(0)
0 个相关的物种来源信息
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：
- PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。
| 亚细胞结构定位 | 关联基因列表 |
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文献列表
- Luoying Li, Yifan Zhang, Yan Gao, Yaqi Hu, Rui Wang, Shuwen Wang, Yuanyang Li, Yumin He, Chengfu Yuan. LncSNHG14 promotes nutlin3a resistance by inhibiting ferroptosis via the miR-206 /SLC7A11 axis in osteosarcoma cells.
Cancer gene therapy.
2023 05; 30(5):704-715. doi:
10.1038/s41417-022-00581-z. [PMID: 36599973] - Sahar Javadi, Yue Li, Jie Sheng, Lucy Zhao, Yao Fu, Daifeng Wang, Xinyu Zhao. Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of fragile X syndrome.
BMC medicine.
2022 05; 20(1):163. doi:
10.1186/s12916-022-02370-9. [PMID: 35549943] - Yohei Sekino, Kenshiro Takemoto, Daiki Murata, Takashi Babasaki, Kohei Kobatake, Hiroyuki Kitano, Kenichiro Ikeda, Keisuke Goto, Shogo Inoue, Tetsutaro Hayashi, Daiki Taniyama, Masanobu Shigeta, Kazuya Kuraoka, Koji Mita, Mayumi Kaneko, Kazuhiro Sentani, Naohide Oue, Jun Teishima. P53 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma.
Anticancer research.
2021 Sep; 41(9):4287-4294. doi:
10.21873/anticanres.15233. [PMID: 34475048] - Carlotta Pucci, Daniele De Pasquale, Attilio Marino, Chiara Martinelli, Simone Lauciello, Gianni Ciofani. Hybrid Magnetic Nanovectors Promote Selective Glioblastoma Cell Death through a Combined Effect of Lysosomal Membrane Permeabilization and Chemotherapy.
ACS applied materials & interfaces.
2020 Jul; 12(26):29037-29055. doi:
10.1021/acsami.0c05556. [PMID: 32459082] - Eric Zadok Mpingirika, Ahmed El Hosseiny, Sheri Magdy Saleeb Bakheit, Rami Arafeh, Asma Amleh. Potential Anticancer Activity of Crude Ethanol, Ethyl Acetate, and Water Extracts of Ephedra foeminea on Human Osteosarcoma U2OS Cell Viability and Migration.
BioMed research international.
2020; 2020(?):3837693. doi:
10.1155/2020/3837693. [PMID: 32695811] - Swathi Merugu, Lindi Chen, Elizabeth Gavens, Hany Gabra, Mark Brougham, Guy Makin, Antony Ng, Dermot Murphy, Alem S Gabriel, Michael L Robinson, Jennifer H Wright, Susan A Burchill, Angharad Humphreys, Nick Bown, David Jamieson, Deborah A Tweddle. Detection of Circulating and Disseminated Neuroblastoma Cells Using the ImageStream Flow Cytometer for Use as Predictive and Pharmacodynamic Biomarkers.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2020 01; 26(1):122-134. doi:
10.1158/1078-0432.ccr-19-0656. [PMID: 31767563] - Bilge Debelec-Butuner, Mustafa Kotmakci, Ezgi Oner, Gulseren Ozduman, Ayse Gulten Kantarci. Nutlin3a-Loaded Nanoparticles Show Enhanced Apoptotic Activity on Prostate Cancer Cells.
Molecular biotechnology.
2019 Jul; 61(7):489-497. doi:
10.1007/s12033-019-00178-2. [PMID: 31028604] - Agostina Grillone, Matteo Battaglini, Stefania Moscato, Letizia Mattii, César de Julián Fernández, Alice Scarpellini, Mario Giorgi, Edoardo Sinibaldi, Gianni Ciofani. Nutlin-loaded magnetic solid lipid nanoparticles for targeted glioblastoma treatment.
Nanomedicine (London, England).
2019 Mar; 14(6):727-752. doi:
10.2217/nnm-2018-0436. [PMID: 30574827] - Fang-Fang He, Ren-Yu You, Chen Ye, Chun-Tao Lei, Hui Tang, Hua Su, Chun Zhang. Inhibition of SIRT2 Alleviates Fibroblast Activation and Renal Tubulointerstitial Fibrosis via MDM2.
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology.
2018; 46(2):451-460. doi:
10.1159/000488613. [PMID: 29614506] - Junwoo Lee, Sungkwan An, Yeong Min Choi, Jin Hyuk Jung, Li Li, Hong Meng, Yinmao Dong, Kyu Joong Ahn, In-Sook An, Seunghee Bae. TRIAD1 Is a Novel Transcriptional Target of p53 and Regulates Nutlin-3a-Induced Cell Death.
Journal of cellular biochemistry.
2017 07; 118(7):1733-1740. doi:
10.1002/jcb.25831. [PMID: 27935098] - Hao Zhao, Ruijuan Shen, Xiaobin Dong, Yi Shen. Murine Double Minute-2 Inhibition Attenuates Cardiac Dysfunction and Fibrosis by Modulating NF-κB Pathway After Experimental Myocardial Infarction.
Inflammation.
2017 Feb; 40(1):232-239. doi:
10.1007/s10753-016-0473-5. [PMID: 27838797] - Dongmei Lu, Alysha Rauhauser, Binghua Li, Chongyu Ren, Kayla McEnery, Jili Zhu, Moumita Chaki, Komal Vadnagara, Sarah Elhadi, Anton M Jetten, Peter Igarashi, Massimo Attanasio. Loss of Glis2/NPHP7 causes kidney epithelial cell senescence and suppresses cyst growth in the Kif3a mouse model of cystic kidney disease.
Kidney international.
2016 06; 89(6):1307-23. doi:
10.1016/j.kint.2016.03.006. [PMID: 27181777] - Natalia Rueda-Rincon, Katarzyna Bloch, Rita Derua, Rajesh Vyas, Amy Harms, Thomas Hankemeier, Niamat Ali Khan, Jonas Dehairs, Muralidhararao Bagadi, Maria Mercedes Binda, Etienne Waelkens, Jean-Christophe Marine, Johannes V Swinnen. p53 attenuates AKT signaling by modulating membrane phospholipid composition.
Oncotarget.
2015 Aug; 6(25):21240-54. doi:
10.18632/oncotarget.4067. [PMID: 26061814] - Radosław Polański, Aidan P Noon, Jeremy Blaydes, Anna Phillips, Carlos P Rubbi, Keith Parsons, Nikolina Vlatković, Mark T Boyd. Senescence induction in renal carcinoma cells by Nutlin-3: a potential therapeutic strategy based on MDM2 antagonism.
Cancer letters.
2014 Oct; 353(2):211-9. doi:
10.1016/j.canlet.2014.07.024. [PMID: 25067787] - Jing Xiong, Qin Yang, Jiansha Li, Sheng Zhou. Effects of MDM2 inhibitors on vascular endothelial growth factor-mediated tumor angiogenesis in human breast cancer.
Angiogenesis.
2014 Jan; 17(1):37-50. doi:
10.1007/s10456-013-9376-3. [PMID: 23907365] - Shrikant R Mulay, Dana Thomasova, Mi Ryu, Onkar P Kulkarni, Adriana Migliorini, Hauke Bruns, Regina Gröbmayr, Elena Lazzeri, Laura Lasagni, Helen Liapis, Paola Romagnani, Hans-Joachim Anders. Podocyte loss involves MDM2-driven mitotic catastrophe.
The Journal of pathology.
2013 Jul; 230(3):322-35. doi:
10.1002/path.4193. [PMID: 23749457] - Mariana Leão, Sara Gomes, José Pedraza-Chaverri, Neuza Machado, Emília Sousa, Madalena Pinto, Alberto Inga, Clara Pereira, Lucília Saraiva. Α-mangostin and gambogic acid as potential inhibitors of the p53-MDM2 interaction revealed by a yeast approach.
Journal of natural products.
2013 Apr; 76(4):774-8. doi:
10.1021/np400049j. [PMID: 23540934] - Nathalie Mouraret, Elisabeth Marcos, Shariq Abid, Guillaume Gary-Bobo, Mirna Saker, Amal Houssaini, Jean-Luc Dubois-Rande, Laurent Boyer, Jorge Boczkowski, Geneviève Derumeaux, Valérie Amsellem, Serge Adnot. Activation of lung p53 by Nutlin-3a prevents and reverses experimental pulmonary hypertension.
Circulation.
2013 Apr; 127(16):1664-76. doi:
10.1161/circulationaha.113.002434. [PMID: 23513067] - Eun Jung Park, Kyeong Sook Choi, Young Hyun Yoo, Taeg Kyu Kwon. Nutlin-3, a small-molecule MDM2 inhibitor, sensitizes Caki cells to TRAIL-induced apoptosis through p53-mediated PUMA upregulation and ROS-mediated DR5 upregulation.
Anti-cancer drugs.
2013 Mar; 24(3):260-9. doi:
10.1097/cad.0b013e32835c0311. [PMID: 23187459] - Hidehisa Shimizu, Maimaiti Yisireyili, Fuyuhiko Nishijima, Toshimitsu Niwa. Indoxyl sulfate enhances p53-TGF-β1-Smad3 pathway in proximal tubular cells.
American journal of nephrology.
2013; 37(2):97-103. doi:
10.1159/000346420. [PMID: 23363842] - Rit Vatsyayan, Jyotsana Singhal, Lokesh Dalasanur Nagaprashantha, Sanjay Awasthi, Sharad S Singhal. Nutlin-3 enhances sorafenib efficacy in renal cell carcinoma.
Molecular carcinogenesis.
2013 Jan; 52(1):39-48. doi:
10.1002/mc.20875. [PMID: 22006587] - Shrikant R Mulay, Dana Thomasova, Mi Ryu, Hans-Joachim Anders. MDM2 (murine double minute-2) links inflammation and tubular cell healing during acute kidney injury in mice.
Kidney international.
2012 Jun; 81(12):1199-211. doi:
10.1038/ki.2011.482. [PMID: 22297670] - Manasi Das, Sanjeeb K Sahoo. Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.
PloS one.
2012; 7(3):e32920. doi:
10.1371/journal.pone.0032920. [PMID: 22470431] - Ramanjaneyulu Allam, Sufyan G Sayyed, Onkar P Kulkarni, Julia Lichtnekert, Hans-Joachim Anders. Mdm2 promotes systemic lupus erythematosus and lupus nephritis.
Journal of the American Society of Nephrology : JASN.
2011 Nov; 22(11):2016-27. doi:
10.1681/asn.2011010045. [PMID: 21949095] - Christian Tovar, Brian Higgins, Kenneth Kolinsky, Mingxuan Xia, Kathryn Packman, David C Heimbrook, Lyubomir T Vassilev. MDM2 antagonists boost antitumor effect of androgen withdrawal: implications for therapy of prostate cancer.
Molecular cancer.
2011 May; 10(?):49. doi:
10.1186/1476-4598-10-49. [PMID: 21539745] - Fan Zhang, Michael Tagen, Stacy Throm, Jeremy Mallari, Laura Miller, R Kiplin Guy, Michael A Dyer, Richard T Williams, Martine F Roussel, Katie Nemeth, Fangyi Zhu, Jiakun Zhang, Min Lu, John C Panetta, Nidal Boulos, Clinton F Stewart. Whole-body physiologically based pharmacokinetic model for nutlin-3a in mice after intravenous and oral administration.
Drug metabolism and disposition: the biological fate of chemicals.
2011 Jan; 39(1):15-21. doi:
10.1124/dmd.110.035915. [PMID: 20947617] - Chun Chui Tsao, Paul G Corn. MDM-2 antagonists induce p53-dependent cell cycle arrest but not cell death in renal cancer cell lines.
Cancer biology & therapy.
2010 Dec; 10(12):1315-25. doi:
10.4161/cbt.10.12.13612. [PMID: 20953142] - Olga V Leontieva, Mikhail V Blagosklonny. DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence.
Aging.
2010 Dec; 2(12):924-35. doi:
10.18632/aging.100265. [PMID: 21212465] - Manujendra N Saha, Hua Jiang, Hong Chang. Molecular mechanisms of nutlin-induced apoptosis in multiple myeloma: evidence for p53-transcription-dependent and -independent pathways.
Cancer biology & therapy.
2010 Sep; 10(6):567-78. doi:
10.4161/cbt.10.6.12535. [PMID: 20595817] - Feng Bai, Fangyi Zhu, Michael Tagen, Laura Miller, Thandranese S Owens, Jeremy Mallari, Edward Derrick, Fan Zhang, Clinton F Stewart. Determination of nutlin-3a in murine plasma by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).
Journal of pharmaceutical and biomedical analysis.
2010 Mar; 51(4):915-20. doi:
10.1016/j.jpba.2009.10.016. [PMID: 19931997] - Yoon-Mi Lee, Ji-Hong Lim, Yang-Sook Chun, Hyo-Eun Moon, Myung Kyu Lee, L Eric Huang, Jong-Wan Park. Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1alpha.
Carcinogenesis.
2009 Oct; 30(10):1768-75. doi:
10.1093/carcin/bgp196. [PMID: 19696166] - Martin Michaelis, Florian Rothweiler, Denise Klassert, Andreas von Deimling, Kristoffer Weber, Boris Fehse, Bernd Kammerer, Hans Wilhelm Doerr, Jindrich Cinatl. Reversal of P-glycoprotein-mediated multidrug resistance by the murine double minute 2 antagonist nutlin-3.
Cancer research.
2009 Jan; 69(2):416-21. doi:
10.1158/0008-5472.can-08-1856. [PMID: 19147553] - Guangping Chen, Haidong Huang, Otto Fröhlich, Yuan Yang, Janet D Klein, S Russ Price, Jeff M Sands. MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation.
American journal of physiology. Renal physiology.
2008 Nov; 295(5):F1528-34. doi:
10.1152/ajprenal.90482.2008. [PMID: 18784257] - Ian R Logan, Hesta V McNeill, Susan Cook, Xiaohong Lu, John Lunec, Craig N Robson. Analysis of the MDM2 antagonist nutlin-3 in human prostate cancer cells.
The Prostate.
2007 Jun; 67(8):900-6. doi:
10.1002/pros.20568. [PMID: 17440969] - Man Jiang, Navjotsin Pabla, Robert F Murphy, Tianxin Yang, Xiao-Ming Yin, Kurt Degenhardt, Eileen White, Zheng Dong. Nutlin-3 protects kidney cells during cisplatin therapy by suppressing Bax/Bak activation.
The Journal of biological chemistry.
2007 Jan; 282(4):2636-45. doi:
10.1074/jbc.m606928200. [PMID: 17130128] - D S Gilbert. Axoplasm chemical composition in Myxicola and solubility properties of its structural proteins.
The Journal of physiology.
1975 Dec; 253(1):303-19. doi:
10.1113/jphysiol.1975.sp011191. [PMID: 1260]
