Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T00176
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| Former ID |
TTDC00206
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| Target Name |
Ubiquitin-protein ligase E3 Mdm2
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| Gene Name |
MDM2
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| Synonyms |
Double minute 2 protein; Hdm2; MDM2 protein; Oncoprotein Mdm2; P53-binding protein Mdm2; MDM2
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| Target Type |
Clinical Trial
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| Disease | Acute myeloid leukemia [ICD9: 205; ICD10: C92.0] | ||||
| Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
| Hematological malignancies [ICD9: 200-209; ICD10: C81-C86] | |||||
| Non-small cell lung cancer; Prostate cancer [ICD9:185; ICD10: C33-C34, C61] | |||||
| Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
| Function |
Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Functions as a ubiquitin ligase e3, in the presence of e1 and e2, toward p53 and itself. Permits the nuclear export ofp53 and targets it.
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| BioChemical Class |
Carbon-nitrogen ligase
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| Target Validation |
T00176
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| UniProt ID | |||||
| EC Number |
EC 6.3.2.-
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| Sequence |
MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQY
IMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGT SVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQ RKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDS VSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLA DYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVP DCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQ DKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQ PIQMIVLTYFP |
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| Drugs and Mode of Action | |||||
| Drug(s) | AMG 232 | Drug Info | Phase 1/2 | Cancer | [524711] |
| DS-3032 | Drug Info | Phase 1 | Solid tumours | [524327] | |
| JNJ-26854165 | Drug Info | Phase 1 | Non-small cell lung cancer; Prostate cancer | [522321] | |
| RG7388 | Drug Info | Phase 1 | Hematological malignancies | [525138] | |
| RG7775 | Drug Info | Phase 1 | Acute myeloid leukemia | [549548] | |
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| Pathways | |||||
| KEGG Pathway | FoxO signaling pathway | ||||
| Cell cycle | |||||
| p53 signaling pathway | |||||
| Ubiquitin mediated proteolysis | |||||
| Endocytosis | |||||
| PI3K-Akt signaling pathway | |||||
| Thyroid hormone signaling pathway | |||||
| Epstein-Barr virus infection | |||||
| Pathways in cancer | |||||
| Transcriptional misregulation in cancer | |||||
| Viral carcinogenesis | |||||
| Proteoglycans in cancer | |||||
| MicroRNAs in cancer | |||||
| Glioma | |||||
| Prostate cancer | |||||
| Melanoma | |||||
| Bladder cancer | |||||
| Chronic myeloid leukemia | |||||
| PANTHER Pathway | Insulin/IGF pathway-protein kinase B signaling cascade | ||||
| p53 pathway | |||||
| Ubiquitin proteasome pathway | |||||
| P53 pathway feedback loops 1 | |||||
| p53 pathway feedback loops 2 | |||||
| Pathway Interaction Database | ErbB4 signaling events | ||||
| p73 transcription factor network | |||||
| ATR signaling pathway | |||||
| ATM pathway | |||||
| Glucocorticoid receptor regulatory network | |||||
| Sumoylation by RanBP2 regulates transcriptional repression | |||||
| Direct p53 effectors | |||||
| Regulation of Androgen receptor activity | |||||
| Validated transcriptional targets of deltaNp63 isoforms | |||||
| Aurora A signaling | |||||
| Validated transcriptional targets of TAp63 isoforms | |||||
| p53 pathway | |||||
| Regulation of retinoblastoma protein | |||||
| Reactome | AKT phosphorylates targets in the cytosol | ||||
| Oxidative Stress Induced Senescence | |||||
| Oncogene Induced Senescence | |||||
| Trafficking of AMPA receptors | |||||
| Constitutive Signaling by AKT1 E17K in Cancer | |||||
| Stabilization of p53 | |||||
| WikiPathways | DNA Damage Response (only ATM dependent) | ||||
| DNA Damage Response | |||||
| ErbB Signaling Pathway | |||||
| Senescence and Autophagy in Cancer | |||||
| Tryptophan metabolism | |||||
| G1 to S cell cycle control | |||||
| Copper homeostasis | |||||
| Bladder Cancer | |||||
| Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | |||||
| PIP3 activates AKT signaling | |||||
| Apoptosis | |||||
| ATM Signaling Pathway | |||||
| Retinoblastoma (RB) in Cancer | |||||
| Integrated Pancreatic Cancer Pathway | |||||
| Prostate Cancer | |||||
| Signaling Pathways in Glioblastoma | |||||
| Integrated Breast Cancer Pathway | |||||
| Integrated Cancer pathway | |||||
| Cell Cycle | |||||
| Cell Cycle Checkpoints | |||||
| TP53 Network | |||||
| miRNA Regulation of DNA Damage Response | |||||
| Androgen receptor signaling pathway | |||||
| References | |||||
| Ref 522321 | ClinicalTrials.gov (NCT00676910) A Research Study of JNJ-26854165 to Determine the Safety and Dose in Patients With Advanced Stage or Refractory Solid Tumors.. U.S. National Institutes of Health. | ||||
| Ref 524327 | ClinicalTrials.gov (NCT01877382) A Phase 1 Multiple Ascending Dose Study of DS-3032b, an Oral Murine Double Minute 2 (MDM2) Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas. U.S. National Institutes of Health. | ||||
| Ref 524711 | ClinicalTrials.gov (NCT02110355) A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma. U.S. National Institutes of Health. | ||||
| Ref 525403 | Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014 Mar;13(3):217-36. doi: 10.1038/nrd4236. | ||||
| Ref 532478 | Serdemetan antagonizes the Mdm2-HIF1alpha axis leading to decreased levels of glycolytic enzymes. PLoS One. 2013 Sep 6;8(9):e74741. | ||||
| Ref 532858 | Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J Med Chem. 2014 Aug 14;57(15):6332-41. | ||||
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