Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT9TE0O)

DTT Name	Mdm2 messenger RNA (MDM2 mRNA)
Synonyms	RING-type E3 ubiquitin transferase Mdm2 (mRNA); P53-binding protein Mdm2 (mRNA); Oncoprotein Mdm2 (mRNA); MDM2 protein (mRNA); Hdm2 (mRNA); E3 ubiquitin-protein ligase Mdm2 (mRNA); Double minute 2 protein (mRNA)
Gene Name	MDM2
DTT Type	Literature-reported target	[1]
BioChemical Class	mRNA target
UniProt ID	MDM2_HUMAN
TTD ID	T10937
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 2.3.2.27
Sequence	MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQY IMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGT SVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQ RKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDS VSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLA DYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVP DCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQ DKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQ PIQMIVLTYFP
Function	Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation. Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells. Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis. E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome.
KEGG Pathway	FoxO signaling pathway (hsa04068 ) Cell cycle (hsa04110 ) p53 signaling pathway (hsa04115 ) Ubiquitin mediated proteolysis (hsa04120 ) Endocytosis (hsa04144 ) PI3K-Akt signaling pathway (hsa04151 ) Thyroid hormone signaling pathway (hsa04919 ) Epstein-Barr virus infection (hsa05169 ) Pathways in cancer (hsa05200 ) Transcriptional misregulation in cancer (hsa05202 ) Viral carcinogenesis (hsa05203 ) Proteoglycans in cancer (hsa05205 ) MicroRNAs in cancer (hsa05206 ) Glioma (hsa05214 ) Prostate cancer (hsa05215 ) Melanoma (hsa05218 ) Bladder cancer (hsa05219 ) Chronic myeloid leukemia (hsa05220 )
Reactome Pathway	Oxidative Stress Induced Senescence (R-HSA-2559580 ) Oncogene Induced Senescence (R-HSA-2559585 ) Trafficking of AMPA receptors (R-HSA-399719 ) Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400 ) Stabilization of p53 (R-HSA-69541 ) AKT phosphorylates targets in the cytosol (R-HSA-198323 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DTT

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 16507	DMK69ZR	Solid tumour/cancer	2A00-2F9Z	Investigative	[1]
ISIS 16518	DM24L0S	Solid tumour/cancer	2A00-2F9Z	Investigative	[1]
NSC-66811	DMRVMA5	Discovery agent	N.A.	Investigative	[2]
NU-8231	DMEUV5R	Discovery agent	N.A.	Investigative	[3]
NUTLIN-3	DM5KXFI	Discovery agent	N.A.	Investigative	[4]
PLSQETFSDLWKLLPEN-NH2	DMBN4V6	Discovery agent	N.A.	Investigative	[5]
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⏷ Show the Full List of 6 Investigative Drug(s)

References

1	US patent application no. 6,238,921, Antisense oligonucleotide modulation of human mdm2 expression.
2	Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening str... J Med Chem. 2006 Jun 29;49(13):3759-62.
3	Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. J Med Chem. 2006 Oct 19;49(21):6209-21.
4	Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature. 2007 Dec 13;450(7172):1001-9.
5	Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. J Med Chem. 2006 Jun 15;49(12):3432-5.