pevonedistat

a potent and selective inhibitor of NAE (NEDD8-activating enzyme)

Also Known As:

((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate; ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulphamate; 4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)-2-hydroxycyclopentyl methyl sulfamidate; MLN-4924; MLN4924

Networked: 270 relevant articles (25 outcomes, 92 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Sun, Yi: 25 articles (01/2022 - 01/2011)
2.	Jia, Lijun: 25 articles (12/2020 - 06/2011)
3.	Li, Lihui: 16 articles (12/2020 - 07/2012)
4.	Jeong, Lak Shin: 14 articles (11/2020 - 07/2012)
5.	Smith, Peter G: 14 articles (11/2016 - 05/2010)
6.	Liang, Yupei: 11 articles (12/2020 - 01/2014)
7.	Yu, Jinha: 9 articles (11/2020 - 06/2014)
8.	Sedarati, Farhad: 8 articles (11/2022 - 05/2015)
9.	Zhang, Wenjuan: 8 articles (12/2020 - 06/2016)
10.	Zhao, Hu: 8 articles (01/2020 - 01/2014)

Related Diseases

1.	Neoplasms (Cancer) 09/11/2017 - "We further demonstrated that the combination treatment was markedly effective in subcutaneous tumor xenograft models as well as in a disseminated model of AML, leading to tumor eradication or prolonged survival in T-3775440/pevonedistat cotreated mice. " 04/11/2016 - "Given that CRLs components are up-regulated, whereas neddylation modification is over-activated in a number of human cancers, MLN4924 was found to be effective in growth suppression of cancer cells. " 01/01/2023 - "Meanwhile, loss of UBE2M in tumor did not alter efficacy of pevonedistat. " 01/01/2022 - "Several I/II/III clinical trials suggested that MLN4924 exerts an antitumor effect against various malignancies. " 01/01/2021 - "Here we report the results of a phase I trial characterizing the mass balance, pharmacokinetics, and clearance pathways of [14C]-pevonedistat in patients with advanced solid tumors (NCT03057366). "
2.	Stomach Neoplasms (Stomach Cancer) 04/11/2016 - "Whether MLN4924 is effective against gastric cancer cells, however, remains elusive. " 08/27/2015 - "In summary, our findings unveiled a protective role of P27 by maintaining mitochondrial membrane permeability in MLN4924-treated gastric cancer cells, and therefore highlighted the potential combination of MLN4924 with P27 inhibition to improve its therapeutic efficacy. " 08/27/2015 - "In this study, MLN4924 induced significant growth inhibition of gastric cancer cells in a dose-dependent manner, along with the simultaneous accumulation of P27 and cell cycle abnormalities such as G2/M arrest. " 12/01/2018 - "We showed a protective role of MRFAP1 in gastric cancer cells with MLN4924 treatment and suggested the potential possibility to combine MLN4924 with MRFAP1 inhibition to treat gastric cancer." 12/01/2018 - "CRISPR-mediated knockout of MRFAP1 increased the cytotoxicity of MLN4924 by augmenting MLN4924-induced G2/M arrest and apoptosis against gastric cancer cells. "
3.	Liver Neoplasms (Liver Cancer) 11/01/2022 - "Ectopic expression of IκBα enhanced the antitumor potential of MLN4924 in liver cancer cells. " 11/01/2022 - "However, the sensitivity of MLN4924 in liver cancer remains unsatisfactory due to factors causing resistance. " 04/20/2015 - "We reported previously that inhibition of neddylation pathway with specific NAE inhibitor MLN4924, suppressed the malignant phenotypes of liver cancer. " 07/01/2012 - "In a xenograft model of human liver cancer, MLN4924 was well-tolerated and displayed a significant antitumor effect characterized by CRL inactivation and induction of autophagy and apoptosis in liver cancer cells. " 07/01/2012 - "Here, we report that MLN4924 also triggers autophagy in response to CRL inactivation and that this effect is important for the ability of MLN4924 to suppress the outgrowth of liver cancer cells in vitro and in vivo. "
4.	Melanoma (Melanoma, Malignant) 08/01/2016 - "Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma." 10/01/2018 - "These results show that MLN4924 does have an efficacy in treating melanoma in vitro alone or in combination with IFN-α, and thus it may have potential use in patients with advanced melanoma." 09/01/2020 - "These results provided justification for further exploration of MLN4924 as a treatment of canine melanoma." 09/01/2020 - "MLN4924 treatment significantly reduced the viability of canine melanoma cell lines and primary samples in a dose- and time-dependent manners. " 10/01/2018 - "Results from MTS proliferation assays indicate that MLN4924 has antiproliferative effects on melanoma cells in vitro, with the addition of IFN-α further inhibiting proliferation. "
5.	Squamous Cell Carcinoma of Head and Neck 12/01/2011 - "This study reveals a novel function of MLN4924 in synergizing with TRAIL to induce apoptosis in HNSCC cells. " 09/09/2023 - "Taken together, our results suggest that combined treatment with MLN4924 and 10-HCPT may be an effective strategy in HNSCC." 09/09/2023 - "Importantly, neddylation inhibition with MLN4924 acts synergistically with 10-HCPT to suppress cell growth, migration and apoptosis in HNSCC cells. " 01/01/2018 - "Pevonedistat additionally sensitizes HNSCC cells to ionizing radiation (IR) and enhances IR-induced suppression of xenografts in mice. " 12/01/2011 - "MLN4924 alone effectively inhibited the growth of HNSCC cells and induced apoptosis. "

Related Drugs and Biologics

1.	pevonedistat
2.	Cisplatin (Platino)
3.	Enzyme Inhibitors (Inhibitors, Enzyme)
4.	Enzymes
5.	Platinum
6.	Ubiquitin-Protein Ligases (Ubiquitin-Protein Ligase)
7.	Cullin Proteins (Cullins)
8.	Paclitaxel (Taxol)
9.	Oxaliplatin (Eloxatin)
10.	Capecitabine (Xeloda)

Related Therapies and Procedures

1.	Drug Therapy (Chemotherapy)
2.	Therapeutics
3.	Aftercare (After-Treatment)
4.	Intravenous Administration
5.	Oncolytic Virotherapy