Pevonedistat (BioDeep_00000760357)
代谢物信息卡片
Pevonedistat
化学式: C21H25N5O4S (443.1627)
中文名称: MLN-4924
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: C1CC2=CC=CC=C2C1NC3=C4C=CN(C4=NC=N3)C5CC(C(C5)O)COS(=O)(=O)N
InChI: InChI=1S/C21H25N5O4S/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25)/t14-,15+,18-,19-/m0/s1
描述信息
C274 - Antineoplastic Agent > C2189 - Signal Transduction Inhibitor > C129824 - Antineoplastic Protein Inhibitor
C471 - Enzyme Inhibitor > C129825 - Antineoplastic Enzyme Inhibitor
D004791 - Enzyme Inhibitors
同义名列表
2 个代谢物同义名
数据库引用编号
7 个数据库交叉引用编号
- ChEBI: CHEBI:145535
- ChEBI: CHEBI:95028
- KEGGdrug: D10413
- PubChem: 16720766
- DrugBank: DB11759
- ChEMBL: CHEMBL1231160
- CAS: 905579-51-3
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 |
|---|
文献列表
- Mengjuan Chen, Yuqing Liu, Mingzhong Zuo, Meina Zhang, Zhitong Wang, Xin Li, Dongdong Yuan, Huifen Xu, Guangqing Yu, Ming Li. Integrated analysis reveals the regulatory mechanism of the neddylation inhibitor MLN4924 on the metabolic dysregulation in rabbit granulosa cells.
BMC genomics.
2024 Mar; 25(1):254. doi:
10.1186/s12864-024-10118-3. [PMID: 38448814] - Haojun Xiong, Dandan Zheng, Ying Liu, Lihai Ma, Lingzhan Meng, Zhenzhou Yang, Zhixiang Yang. Activation of the β‑TrCP/IκBα/inflammation axis limits the sensitivity of liver cancer cells to neddylation inhibition.
Oncology reports.
2022 Nov; 48(5):. doi:
10.3892/or.2022.8416. [PMID: 36169173] - Jayaprakasam Bolleddula, Hao Chen, Lawrence Cohen, Xiaofei Zhou, Sandeepraj Pusalkar, Allison Berger, Farhad Sedarati, Karthik Venkatakrishnan, Swapan K Chowdhury. Metabolism and Disposition of [14C]Pevonedistat, a First-in-Class NEDD8-Activating Enzyme Inhibitor, after Intravenous Infusion to Patients with Advanced Solid Tumors.
Drug metabolism and disposition: the biological fate of chemicals.
2022 Jul; 50(7):989-997. doi:
10.1124/dmd.122.000842. [PMID: 35504658] - Philip Sandoval, Bei-Ching Chuang, Lawrence Cohen, Tomoki Yoneyama, Sandeepraj Pusalkar, Robert W Yucha, Swapan K Chowdhury, Paresh P Chothe. Sinusoidal Uptake Determines the Hepatic Clearance of Pevonedistat (TAK-924) as Explained by Extended Clearance Model.
Drug metabolism and disposition: the biological fate of chemicals.
2022 Jul; 50(7):980-988. doi:
10.1124/dmd.122.000836. [PMID: 35545257] - Qi Liang, Maoyu Liu, Jian Li, Rongsheng Tong, Yonghe Hu, Lan Bai, Jianyou Shi. NAE modulators: A potential therapy for gastric carcinoma.
European journal of medicinal chemistry.
2022 Mar; 231(?):114156. doi:
10.1016/j.ejmech.2022.114156. [PMID: 35131538] - Sathish K Murali, Robert Little, Søren B Poulsen, Mohammed Z Ferdaus, David H Ellison, James A McCormick, Robert A Fenton. Potassium Effects on NCC Are Attenuated during Inhibition of Cullin E3-Ubiquitin Ligases.
Cells.
2021 12; 11(1):. doi:
10.3390/cells11010095. [PMID: 35011657] - Kankan Wang, Kurt M Reichermeier, Xing Liu. Quantitative analyses for effects of neddylation on CRL2VHL substrate ubiquitination and degradation.
Protein science : a publication of the Protein Society.
2021 11; 30(11):2338-2345. doi:
10.1002/pro.4176. [PMID: 34459035] - Yousra M El-Far, Mohamed El-Mesery. Pevonedistat attenuates cisplatin-induced nephrotoxicity in mice by downregulating the release of inflammatory mediators.
Journal of biochemical and molecular toxicology.
2021 Nov; 35(11):e22908. doi:
10.1002/jbt.22908. [PMID: 34476871] - Ji Zhang, Jing Cui, Fei Zhao, Longhua Yang, Xueli Xu, Yangyang Shi, Bo Wei. Cardioprotective effect of MLN4924 on ameliorating autophagic flux impairment in myocardial ischemia-reperfusion injury by Sirt1.
Redox biology.
2021 10; 46(?):102114. doi:
10.1016/j.redox.2021.102114. [PMID: 34454165] - Sara Petillo, Cristina Capuano, Rosa Molfetta, Cinzia Fionda, Abdelilah Mekhloufi, Chiara Pighi, Fabrizio Antonangeli, Alessandra Zingoni, Alessandra Soriani, Maria Teresa Petrucci, Ricciarda Galandrini, Rossella Paolini, Angela Santoni, Marco Cippitelli. Immunomodulatory effect of NEDD8-activating enzyme inhibition in Multiple Myeloma: upregulation of NKG2D ligands and sensitization to Natural Killer cell recognition.
Cell death & disease.
2021 09; 12(9):836. doi:
10.1038/s41419-021-04104-w. [PMID: 34482362] - Xiaofei Zhou, Farhad Sedarati, Douglas V Faller, Dan Zhao, Hélène M Faessel, Swapan Chowdhury, Jayaprakasam Bolleddula, Yuexian Li, Karthik Venkatakrishnan, Zsuzsanna Papai. Phase I study assessing the mass balance, pharmacokinetics, and excretion of [14C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors.
Investigational new drugs.
2021 04; 39(2):488-498. doi:
10.1007/s10637-020-01017-x. [PMID: 33089874] - Yuli Lin, Yusheng Chen, Wenxue Feng, Rong Hua, Junfeng Zhang, Yanmiao Huo, Hong Jiang, Bo Yin, Xuguang Yang. Neddylation pathway alleviates chronic pancreatitis by reducing HIF1α-CCL5-dependent macrophage infiltration.
Cell death & disease.
2021 03; 12(3):273. doi:
10.1038/s41419-021-03549-3. [PMID: 33723230] - Xin Chen, Xi Yang, Fei Mao, Jinlian Wei, Yixiang Xu, Baoli Li, Jin Zhu, Shuaishuai Ni, Lijun Jia, Jian Li. Development of novel benzimidazole-derived neddylation inhibitors for suppressing tumor growth invitro and invivo.
European journal of medicinal chemistry.
2021 Jan; 210(?):112964. doi:
10.1016/j.ejmech.2020.112964. [PMID: 33129593] - Yanyu Jiang, Wei Cheng, Lihui Li, Lisha Zhou, Yupei Liang, Wenjuan Zhang, Wenlian Chen, Shiwen Wang, Hu Zhao, Guoan Chen, Wenjun Zhou, Guang Ji, Yanmei Zhang, Robert M Hoffman, Mingsong Wang, Lijun Jia. Effective targeting of the ubiquitin-like modifier NEDD8 for lung adenocarcinoma treatment.
Cell biology and toxicology.
2020 08; 36(4):349-364. doi:
10.1007/s10565-019-09503-6. [PMID: 31907687] - Yupei Liang, Yanyu Jiang, Xing Jin, Ping Chen, Yongqing Heng, Lili Cai, Wenjuan Zhang, Lihui Li, Lijun Jia. Neddylation inhibition activates the protective autophagy through NF-κB-catalase-ATF3 Axis in human esophageal cancer cells.
Cell communication and signaling : CCS.
2020 05; 18(1):72. doi:
10.1186/s12964-020-00576-z. [PMID: 32398095] - Shuaishuai Ni, Xin Chen, Qing Yu, Yixiang Xu, Zhiguo Hu, Junqian Zhang, Wenjuan Zhang, Baoli Li, Xi Yang, Fei Mao, Jing Huang, Yi Sun, Jian Li, Lijun Jia. Discovery of candesartan cilexetic as a novel neddylation inhibitor for suppressing tumor growth.
European journal of medicinal chemistry.
2020 Jan; 185(?):111848. doi:
10.1016/j.ejmech.2019.111848. [PMID: 31732254] - Lili Cai, Liang Liu, Lihui Li, Lijun Jia. SCFFBXO28-mediated self-ubiquitination of FBXO28 promotes its degradation.
Cellular signalling.
2020 01; 65(?):109440. doi:
10.1016/j.cellsig.2019.109440. [PMID: 31678254] - Lisha Zhou, Lijun Jia. Targeting Protein Neddylation for Cancer Therapy.
Advances in experimental medicine and biology.
2020; 1217(?):297-315. doi:
10.1007/978-981-15-1025-0_18. [PMID: 31898235] - Guang Lu, Juan Yi, Andrea Gubas, Ya-Ting Wang, Yihua Wu, Yi Ren, Man Wu, Yin Shi, Chenxi Ouyang, Hayden Weng Siong Tan, Tianru Wang, Liming Wang, Nai-Di Yang, Shuo Deng, Dajing Xia, Ruey-Hwa Chen, Sharon A Tooze, Han-Ming Shen. Suppression of autophagy during mitosis via CUL4-RING ubiquitin ligases-mediated WIPI2 polyubiquitination and proteasomal degradation.
Autophagy.
2019 11; 15(11):1917-1934. doi:
10.1080/15548627.2019.1596484. [PMID: 30898011] - Hongmei Mao, Zaiming Tang, Hua Li, Bo Sun, Mingjia Tan, Shaohua Fan, Yuan Zhu, Yi Sun. Neddylation inhibitor MLN4924 suppresses cilia formation by modulating AKT1.
Protein & cell.
2019 10; 10(10):726-744. doi:
10.1007/s13238-019-0614-3. [PMID: 30850948] - Lihui Li, Jihui Kang, Wenjuan Zhang, Lili Cai, Shiwen Wang, Yupei Liang, Yanyu Jiang, Xiaojun Liu, Yunjing Zhang, Hongfeng Ruan, Guoan Chen, Mingsong Wang, Lijun Jia. Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer.
EBioMedicine.
2019 Jul; 45(?):81-91. doi:
10.1016/j.ebiom.2019.06.005. [PMID: 31208947] - Xiaoqing Jia, Chunjie Li, Lihui Li, Xiaoli Liu, Lisha Zhou, Wenjuan Zhang, Shuaishuai Ni, Yun Lu, Li Chen, Lak Shin Jeong, Jinha Yu, Yingjian Zhang, Jianping Zhang, Simin He, Xin Hu, Hefen Sun, Keda Yu, Guangyu Liu, Hu Zhao, Yanmei Zhang, Lijun Jia, Zhi-Ming Shao. Neddylation Inactivation Facilitates FOXO3a Nuclear Export to Suppress Estrogen Receptor Transcription and Improve Fulvestrant Sensitivity.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2019 06; 25(12):3658-3672. doi:
10.1158/1078-0432.ccr-18-2434. [PMID: 30833270] - Yanyu Jiang, Yupei Liang, Lihui Li, Lisha Zhou, Wei Cheng, Xi Yang, Xuguang Yang, Hui Qi, Jinha Yu, Lak Shin Jeong, Robert M Hoffman, Peiyong Zheng, Lijun Jia. Targeting neddylation inhibits intravascular survival and extravasation of cancer cells to prevent lung-cancer metastasis.
Cell biology and toxicology.
2019 06; 35(3):233-245. doi:
10.1007/s10565-019-09472-w. [PMID: 31140025] - Lisha Zhou, Yanyu Jiang, Qin Luo, Lihui Li, Lijun Jia. Neddylation: a novel modulator of the tumor microenvironment.
Molecular cancer.
2019 04; 18(1):77. doi:
10.1186/s12943-019-0979-1. [PMID: 30943988] - Wenjuan Zhang, Yupei Liang, Lihui Li, Xiaofang Wang, Zi Yan, Changsheng Dong, Mu-Sheng Zeng, Qian Zhong, Xue-Kui Liu, Jinha Yu, Shuyang Sun, Xiaojun Liu, Jihui Kang, Hu Zhao, Lak Shin Jeong, Yanmei Zhang, Lijun Jia. The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma.
Cell proliferation.
2019 Mar; 52(2):e12536. doi:
10.1111/cpr.12536. [PMID: 30341788] - Bo Xu, Yuyou Deng, Ran Bi, Haoran Guo, Chang Shu, Neelam Kumari Shah, Junliang Chang, Guanchen Liu, Yujun Du, Wei Wei, Chunxi Wang. A first-in-class inhibitor, MLN4924 (pevonedistat), induces cell-cycle arrest, senescence, and apoptosis in human renal cell carcinoma by suppressing UBE2M-dependent neddylation modification.
Cancer chemotherapy and pharmacology.
2018 06; 81(6):1083-1093. doi:
10.1007/s00280-018-3582-z. [PMID: 29667067] - Lisha Zhou, Wenjuan Zhang, Yi Sun, Lijun Jia. Protein neddylation and its alterations in human cancers for targeted therapy.
Cellular signalling.
2018 04; 44(?):92-102. doi:
10.1016/j.cellsig.2018.01.009. [PMID: 29331584] - Tang-Jun Ai, Jian-Yong Sun, Lin-Juan Du, Chaoji Shi, Chao Li, Xue-Nan Sun, Yan Liu, Lihui Li, Zhixiong Xia, Lijun Jia, Jianmiao Liu, Sheng-Zhong Duan. Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes apoptosis of vascular smooth muscle cells through p53 and p62.
Cell death and differentiation.
2018 02; 25(2):319-329. doi:
10.1038/cdd.2017.160. [PMID: 29027989] - Pey-Jium Chang, Lee-Wen Chen, Li-Yu Chen, Chien-Hui Hung, Ying-Ju Shih, Shie-Shan Wang. Effects of the NEDD8-Activating Enzyme Inhibitor MLN4924 on Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus.
Journal of virology.
2017 10; 91(19):. doi:
10.1128/jvi.00505-17. [PMID: 28701396] - Jiyou Wang, Shiwen Wang, Wenjuan Zhang, Xiaofang Wang, Xiaojun Liu, Liang Liu, Lihui Li, Yupei Liang, Jinha Yu, Lak Shin Jeong, Lijun Jia, Hu Zhao, Yanmei Zhang. Targeting neddylation pathway with MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis in renal cell carcinoma.
Biochemical and biophysical research communications.
2017 09; 490(4):1183-1188. doi:
10.1016/j.bbrc.2017.06.179. [PMID: 28669728] - Shuai Tong, Yang Si, Hefen Yu, Lingqiang Zhang, Ping Xie, Wenguo Jiang. MLN4924 (Pevonedistat), a protein neddylation inhibitor, suppresses proliferation and migration of human clear cell renal cell carcinoma.
Scientific reports.
2017 07; 7(1):5599. doi:
10.1038/s41598-017-06098-y. [PMID: 28717191] - Xiaojun Liu, Yanan Jiang, Jianfu Wu, Wenjuan Zhang, Yupei Liang, Lijun Jia, Jinha Yu, L S Jeong, Lihui Li. NEDD8-activating enzyme inhibitor, MLN4924 (Pevonedistat) induces NOXA-dependent apoptosis through up-regulation of ATF-4.
Biochemical and biophysical research communications.
2017 06; 488(1):1-5. doi:
10.1016/j.bbrc.2017.04.122. [PMID: 28450112] - Hua Li, Weihua Zhou, Lihui Li, Jianfu Wu, Xiaoli Liu, Lili Zhao, Lijun Jia, Yi Sun. Inhibition of Neddylation Modification Sensitizes Pancreatic Cancer Cells to Gemcitabine.
Neoplasia (New York, N.Y.).
2017 Jun; 19(6):509-518. doi:
10.1016/j.neo.2017.04.003. [PMID: 28535453] - H-S Park, U-I Ju, J-W Park, J Y Song, D H Shin, K-H Lee, L S Jeong, J Yu, H W Lee, J Y Cho, S Y Kim, S W Kim, J B Kim, K S Park, Y-S Chun. PPARγ neddylation essential for adipogenesis is a potential target for treating obesity.
Cell death and differentiation.
2016 08; 23(8):1296-311. doi:
10.1038/cdd.2016.6. [PMID: 26990658] - Jatin J Shah, Andrzej J Jakubowiak, Owen A O'Connor, Robert Z Orlowski, R Donald Harvey, Mitchell R Smith, Daniel Lebovic, Catherine Diefenbach, Kevin Kelly, Zhaowei Hua, Allison J Berger, George Mulligan, Hélène M Faessel, Stephen Tirrell, Bruce J Dezube, Sagar Lonial. Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2016 Jan; 22(1):34-43. doi:
10.1158/1078-0432.ccr-15-1237. [PMID: 26561559] - Junwei Huang, Yi Zhou, Gregory S Thomas, Zhimin Gu, Ye Yang, Hongwei Xu, Guido Tricot, Fenghuang Zhan. NEDD8 Inhibition Overcomes CKS1B-Induced Drug Resistance by Upregulation of p21 in Multiple Myeloma.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2015 Dec; 21(24):5532-42. doi:
10.1158/1078-0432.ccr-15-0254. [PMID: 26156395] - Ronan T Swords, Harry P Erba, Daniel J DeAngelo, Dale L Bixby, Jessica K Altman, Michael Maris, Zhaowei Hua, Stephen J Blakemore, Hélène Faessel, Farhad Sedarati, Bruce J Dezube, Francis J Giles, Bruno C Medeiros. Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study.
British journal of haematology.
2015 May; 169(4):534-43. doi:
10.1111/bjh.13323. [PMID: 25733005] - Yanyan Gu, Jonathan L Kaufman, Leon Bernal, Claire Torre, Shannon M Matulis, R Donald Harvey, Jing Chen, Shi-Yong Sun, Lawrence H Boise, Sagar Lonial. MLN4924, an NAE inhibitor, suppresses AKT and mTOR signaling via upregulation of REDD1 in human myeloma cells.
Blood.
2014 May; 123(21):3269-76. doi:
10.1182/blood-2013-08-521914. [PMID: 24713927] - Yutaka Oono, Akari Nakasone. Lack of SMALL ACIDIC PROTEIN 1 (SMAP1) causes increased sensitivity to an inhibitor of RUB/NEDD8-activating enzyme in Arabidopsis seedlings.
Plant signaling & behavior.
2013 Oct; 8(10):. doi:
10.4161/psb.25986. [PMID: 24270629] - Jana Pia Hakenjos, René Richter, Esther Mirjam Natascha Dohmann, Anthi Katsiarimpa, Erika Isono, Claus Schwechheimer. MLN4924 is an efficient inhibitor of NEDD8 conjugation in plants.
Plant physiology.
2011 Jun; 156(2):527-36. doi:
10.1104/pp.111.176677. [PMID: 21527421]
