Protein Information

General Information of the Protein

Protein ID	PT01771
Protein Name	E3 ubiquitin-protein ligase Mdm2
Secondarily Protein Name	Double minute 2 protein Oncoprotein Mdm2 RING-type E3 ubiquitin transferase Mdm2 p53-binding protein Mdm2
Gene Name	MDM2
Sequence	MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLADYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVPDCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQDKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP Show/Hide
Organism	Homo sapiens, Human
Protein Classification	Other nuclear protein
Function	E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:29681526). 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 a 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 (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). Show/Hide
Uniprot ID	Primary ID: Q00987 Secondarily ID: A6NL51 A8K2S6 Q13226 Q13297 Q13298 Q13299 Q13300 Q13301 Q53XW0 Q71TW9 Q8WYJ1 Q8WYJ2 Q9UGI3 Q9UMT8 Show/Hide
Ensembl ID	ENSG00000135679
HGNC ID	HGNC:6973
Subcellular Location	Nucleus Nucleoplasm Cytoplasm Nucleus Nucleolus Nucleus

Map of Molecular Bioactivity Related to the Protein

Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity

Table of Molecular Bioactivities Related to the Protein

Cell Line ID: CL000083 , MCF-7

Cell Line Info

Compound ID	Compound Name	Compound Formula
CP0208613 Compound Info	1,4-benzodiazepine-2,5-dione, 12k Show/Hide	C31H34Cl2IN5O2	1
1	IC50 = 800 nM Bioactivity Info	TI LI LO TS
CP0285207 Compound Info	1,4-benzodiazepine-2,5-dione scaffold, 21 Show/Hide	C28H28Cl2IN3O4	1
1	IC50 = 1100 nM Bioactivity Info	TI LI LO TS
CP0156321 Compound Info	1,4-benzodiazepine-2,5-dione scaffold, 22 Show/Hide	C29H29Cl2IN4O3	1
1	IC50 = 1300 nM Bioactivity Info	TI LI LO TS
CP0341991 Compound Info	1,4-benzodiazepine-2,5-dione, 12j Show/Hide	C32H32Cl2N4O3	1
1	IC50 = 1700 nM Bioactivity Info	TI LI LO TS
CP0051519 Compound Info	1,4-benzodiazepine-2,5-dione, 12b Show/Hide	C28H25Cl2IN2O4	1
1	IC50 = 7000 nM Bioactivity Info	TI LI LO TS
CP0824303 Compound Info	5-((S)-3-(4-chlorophenyl)-4-(1-(4-chlorophenyl)-2-(diethylamino)-2-oxoethyl)-7-iodo-2,5-dioxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepin-1-yl)pentanoic acid Show/Hide	C32H32Cl2IN3O5	1
1	IC50 = 9000 nM Bioactivity Info	TI LI LO TS
CP0276931 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 23 Show/Hide	C30H26Cl2N2O4	1
1	IC50 = 10300 nM Bioactivity Info	TI LI LO TS
CP0276930 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 24 Show/Hide	C31H28Cl2N2O4	1
1	IC50 = 10700 nM Bioactivity Info	TI LI LO TS
CP0344398 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 21 Show/Hide	C29H25ClF3IN2O4	1
1	IC50 = 11000 nM Bioactivity Info	TI LI LO TS
CP0441433 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 17 Show/Hide	C27H23Cl2IN2O4	1
1	IC50 = 13000 nM Bioactivity Info	TI LI LO TS
CP0170480 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 22 Show/Hide	C29H25ClF3IN2O5	1
1	IC50 = 19000 nM Bioactivity Info	TI LI LO TS
CP0340172 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 2 Show/Hide	C24H17Cl2IN2O4	1
1	IC50 = 24000 nM Bioactivity Info	TI LI LO TS
CP0938798 Compound Info	5-((S)-3-(4-chlorophenyl)-4-(1-(4-chlorophenyl)-2-methoxy-2-oxoethyl)-7-iodo-2,5-dioxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepin-1-yl)pentanoic acid Show/Hide	C29H25Cl2IN2O6	1
1	IC50 = 25000 nM Bioactivity Info	TI LI LO TS
CP0370425 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 5 Show/Hide	C28H24Cl2IN3O5	1
1	IC50 = 31000 nM Bioactivity Info	TI LI LO TS
CP0148360 Compound Info	BMCL163310 Compound 1 Show/Hide	C23H15Cl2IN2O4	1
1	IC50 = 38000 nM Bioactivity Info	TI LI LO TS
CP0940208 Compound Info	5-(4-(carboxy(4-chlorophenyl)methyl)-3-(4-chlorophenyl)-7-iodo-2,5-dioxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepin-1-yl)pentanoic acid Show/Hide	C28H23Cl2IN2O6	1
1	IC50 = 38000 nM Bioactivity Info	TI LI LO TS
CP0340169 Compound Info	1,4-benzodiazepine-2,5-dione scaffold, 2 Show/Hide	C28H26Cl2IN3O4	1
1	IC50 ~ 16000 nM Bioactivity Info	TI LI LO TS

Cell Line ID: CL000111 , MDA-MB-231

Cell Line Info

Cell Line ID: CL000276 , PA-1

Cell Line Info

Cell Line ID: CL000410 , SJSA-1

Cell Line Info

Cell Line ID: CL000102 , U-87MG ATCC

Cell Line Info

Biochemical Assays

Compound ID	Compound Name	Compound Formula
CP0383828 Compound Info	methyl 2-[2-chloro-6-ethoxy-4-[(Z)-(3-methyl-5-oxo-1-phenylpyrazol-4-ylidene)methyl]phenoxy]acetate Show/Hide	C22H21ClN2O5	1
1	EC50 = 840 nM
CP0154204 Compound Info	2-[(3R,5R,6S)-1-[(2S)-1-tert-butylsulfonylbutan-2-yl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid Show/Hide	C28H35Cl2NO5S	2
1	IC50 = 0.1 nM
2	IC50 = 1.1 nM
CP0265582 Compound Info	2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid Show/Hide	C29H35Cl2NO5S	2
1	IC50 = 0.1 nM
2	IC50 = 1.1 nM
CP0176291 Compound Info	2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chloro-2-fluorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid Show/Hide	C29H34Cl2FNO5S	1
1	IC50 < 0.1 nM
CP0292729 Compound Info	US8952036, Ex. 4 Show/Hide	C29H34Cl2FNO5S	1
1	IC50 = 0.1 nM
CP0154215 Compound Info	2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-[(2S)-3-methyl-1-propan-2-ylsulfonylbutan-2-yl]-2-oxopiperidin-3-yl]acetic acid Show/Hide	C28H35Cl2NO5S	4
1	IC50 = 0.6 nM
2	IC50 = 0.63 nM
3	Kd = 0.038 nM
4	Kd = 0.045 nM
CP0041876 Compound Info	(4S,5R)-Nutlin-3 Show/Hide	C30H30Cl2N4O4	18
1	IC50 = 10 nM
2	IC50 = 61 nM
3	IC50 = 70 nM
4	IC50 = 88 nM
5	IC50 = 90 nM
6	IC50 = 100 nM
7	IC50 = 610 nM
8	IC50 = 13600 nM
9	IC50 = 30000 nM
10	Kd = 35 nM
11	Kd = 700 nM
12	Kd < 1000 nM
13	Ki = 6.4 nM
14	Ki = 36 nM
15	Ki = 90 nM
16	Ki = 110 nM
17	Ki = 121 nM
18	Ki = 140 nM
CP0051922 Compound Info	JMC493432 Compound 8 Show/Hide	C29H35Cl2FN4O3	3
1	IC50 = 28.3 nM
2	Ki = 1.7 nM
3	Ki = 3 nM
CP0141684 Compound Info	2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl]acetic acid Show/Hide	C23H23Cl2NO3	1
1	IC50 = 34 nM
CP0227808 Compound Info	(2'R,3S,4'R,5'R)-6-chloro-4'-(3-chlorophenyl)-N-((R)-3,4-dihydroxybutyl)-5-fluoro-2'-neopentyl-2-oxospiro[indoline-3,3'-pyrrolidine]-5'-carboxamide Show/Hide	C27H32Cl2FN3O4	3
1	IC50 = 157 nM
2	Ki = 12.6 nM
3	Ki = 13.3 nM
CP0234556 Compound Info	4-[4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one Show/Hide	C30H30Cl2N4O4	3
1	IC50 = 180 nM
2	Kd = 240 nM
3	Ki = 280 nM
CP0148360 Compound Info	BMCL163310 Compound 1 Show/Hide	C23H15Cl2IN2O4	4
1	IC50 = 200 nM
2	IC50 = 420 nM
3	Kd = 67 nM
4	Kd = 80 nM
CP0340169 Compound Info	1,4-benzodiazepine-2,5-dione scaffold, 2 Show/Hide	C28H26Cl2IN3O4	1
1	IC50 = 250 nM
CP0156321 Compound Info	1,4-benzodiazepine-2,5-dione scaffold, 22 Show/Hide	C29H29Cl2IN4O3	2
1	IC50 = 367 nM
2	IC50 = 790 nM
CP0285207 Compound Info	1,4-benzodiazepine-2,5-dione scaffold, 21 Show/Hide	C28H28Cl2IN3O4	2
1	IC50 = 394 nM
2	IC50 = 700 nM
CP0940208 Compound Info	5-(4-(carboxy(4-chlorophenyl)methyl)-3-(4-chlorophenyl)-7-iodo-2,5-dioxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepin-1-yl)pentanoic acid Show/Hide	C28H23Cl2IN2O6	1
1	IC50 = 510 nM
CP0340172 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 2 Show/Hide	C24H17Cl2IN2O4	1
1	IC50 = 540 nM
CP0208613 Compound Info	1,4-benzodiazepine-2,5-dione, 12k Show/Hide	C31H34Cl2IN5O2	2
1	IC50 = 546 nM
2	IC50 = 704 nM
CP0051519 Compound Info	1,4-benzodiazepine-2,5-dione, 12b Show/Hide	C28H25Cl2IN2O4	2
1	IC50 = 700 nM
2	IC50 = 856 nM
CP0276931 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 23 Show/Hide	C30H26Cl2N2O4	1
1	IC50 = 710 nM
CP0341991 Compound Info	1,4-benzodiazepine-2,5-dione, 12j Show/Hide	C32H32Cl2N4O3	1
1	IC50 = 787 nM
CP0370425 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 5 Show/Hide	C28H24Cl2IN3O5	1
1	IC50 = 870 nM
CP0344398 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 21 Show/Hide	C29H25ClF3IN2O4	1
1	IC50 = 980 nM
CP0170480 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 22 Show/Hide	C29H25ClF3IN2O5	1
1	IC50 = 1040 nM
CP0276930 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 24 Show/Hide	C31H28Cl2N2O4	1
1	IC50 = 1110 nM
CP0824303 Compound Info	5-((S)-3-(4-chlorophenyl)-4-(1-(4-chlorophenyl)-2-(diethylamino)-2-oxoethyl)-7-iodo-2,5-dioxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepin-1-yl)pentanoic acid Show/Hide	C32H32Cl2IN3O5	1
1	IC50 = 2130 nM
CP0938798 Compound Info	5-((S)-3-(4-chlorophenyl)-4-(1-(4-chlorophenyl)-2-methoxy-2-oxoethyl)-7-iodo-2,5-dioxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepin-1-yl)pentanoic acid Show/Hide	C29H25Cl2IN2O6	1
1	IC50 = 2820 nM
CP0441433 Compound Info	1,4-benzodiazepine-2,5-dione antagonist, 17 Show/Hide	C27H23Cl2IN2O4	1
1	IC50 = 8220 nM
CP0267493 Compound Info	4-[(4R,5S)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one Show/Hide	C30H30Cl2N4O4	3
1	IC50 = 13600 nM
2	Kd = 150 nM
3	Ki = 198.4 nM
CP0709749 Compound Info	(3S,4S)-2-(4-chlorobenzyl)-3-(4-chlorophenyl)-N-(2-methoxyethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide Show/Hide	C26H24Cl2N2O3	1
1	Kd = 5000 nM
CP0778805 Compound Info	(3S,4S)-3-(6-chloro-1H-indol-3-yl)-2-(4-chlorobenzyl)-N-(2-(4-methylpiperazin-1-yl)ethyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide Show/Hide	C32H33Cl2N5O2	1
1	Kd = 5000 nM
CP0778804 Compound Info	(3S,4S)-2-(4-chlorobenzyl)-3-(4-chlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid Show/Hide	C23H17Cl2NO3	1
1	Kd = 8000 nM
CP0357029 Compound Info	CHEMBL4537250 Show/Hide	C28H32Cl2FN3O3	1
1	Ki = 0.44 nM
CP0370689 Compound Info	2-[(3R,5S,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1R)-2-methyl-1-propan-2-ylsulfonylpropyl]-2-oxopiperidin-3-yl]acetic acid Show/Hide	C26H31Cl2NO5S	1
1	Ki = 0.6 nM
CP0215907 Compound Info	spiro-oxindole, 1 Show/Hide	C25H29Cl2N3O2	2
1	Ki = 8.5 nM
2	Ki = 86 nM
CP0461657 Compound Info	spiro-oxindole, 4 Show/Hide	C29H36Cl2N4O3	1
1	Ki = 13 nM
CP0157898 Compound Info	(3E)-3-[(2,4-dipropoxyphenyl)methylidene]-1H-indol-2-one Show/Hide	C21H23NO3	1
1	Ki = 230 nM

Clinical Information about the Protein

Target 1 ( Ubiquitin-protein ligase E3 Mdm2 (MDM2) )

Target Type	Clinical trial Target
Disease	5 Target-related Diseases				5
1	Merkel cell carcinoma [ICD-11: 2C34]
2	Prolymphocytic leukaemia [ICD-11: 2A82.1]
3	Haematological malignancy [ICD-11: 2B33.Y]
4	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
5	Triple negative breast cancer [ICD-11: 2C60-2C65]
Clinical Trial Drug(s)	4 Clinical Trial Drugs				4
1	AMG 232	Drug Info	Phase 2	Merkel cell carcinoma
2	APG-115	Drug Info	Phase 2	Prolymphocytic leukaemia
3	HDM201	Drug Info	Phase 1	Haematological malignancy
4	RG7388	Drug Info	Phase 3	Solid tumour/cancer
Investigative Drug(s)	1 Investigative Drug				1
1	MI-219	Drug Info	Investigative	Triple negative breast cancer

Target 2 ( Mdm2 messenger RNA (MDM2 mRNA) )

Target Type	Literature-reported Target

Cite

About MolBiC

Correspondence

Prof. Feng ZHU

Prof. Leo, Lianyi Han