MDM2

Summary

MDM2 (MDM2 proto-oncogene, HGNC:6973) is a protein-coding gene on chromosome 12q15, encoding E3 ubiquitin-protein ligase Mdm2 (Q00987). E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. In precision oncology, MDM2 EXPRESSION is associated with resistance to Pemetrexed + Cisplatin in Malignant Pleural Mesothelioma (CIViC Level B); 1 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 38.4% of cell lines).

This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells.

Source: NCBI Gene 4193 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Li-Fraumeni syndrome (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 174 total — 1 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 38.4% of screened cell lines
• MANE Select transcript: NM_002392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6973
Approved symbol	MDM2
Name	MDM2 proto-oncogene
Location	12q15
Locus type	gene with protein product
Status	Approved
Aliases	HDM2, MGC5370
Ensembl gene	ENSG00000135679
Ensembl biotype	protein_coding
OMIM	164785
Entrez	4193

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 22 protein_coding, 12 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000258148, ENST00000258149, ENST00000299252, ENST00000311420, ENST00000348801, ENST00000350057, ENST00000360430, ENST00000393410, ENST00000393412, ENST00000393413, ENST00000393415, ENST00000393416, ENST00000393417, ENST00000400501, ENST00000471946, ENST00000478070, ENST00000481186, ENST00000493419, ENST00000496959, ENST00000517852, ENST00000523991, ENST00000536089, ENST00000537182, ENST00000539479, ENST00000540352, ENST00000540709, ENST00000542502, ENST00000543046, ENST00000543323, ENST00000544125, ENST00000544561, ENST00000545204, ENST00000546048, ENST00000665020, ENST00000666617, ENST00000671567, ENST00000890006, ENST00000890007, ENST00000951805, ENST00000951806

RefSeq mRNA: 6 — MANE Select: NM_002392 NM_001145337, NM_001145339, NM_001145340, NM_001278462, NM_001367990, NM_002392

CCDS: CCDS61189, CCDS8986, CCDS91724

Canonical transcript exons

ENST00000258149 — 11 exons

Exon	Start	End
ENSE00001919656	68808177	68808491
ENSE00002215052	68839274	68845544
ENSE00003469551	68813554	68813628
ENSE00003476000	68836672	68836749
ENSE00003500719	68809208	68809292
ENSE00003527919	68816812	68816945
ENSE00003597511	68828771	68828931
ENSE00003645279	68835829	68835984
ENSE00003674928	68824555	68824651
ENSE00003683366	68824363	68824430
ENSE00003684852	68820325	68820374

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 97.0053 / max 7331.4544, expressed in 1827 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126620	53.8123	1826
126622	40.0467	1608
126621	1.6264	878
126623	0.3713	139
126636	0.3511	164
126638	0.2367	73
206784	0.2190	90
126637	0.1070	22
90702	0.0962	44
126639	0.0789	15

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.31	gold quality
adrenal tissue	UBERON:0018303	97.33	gold quality
ventricular zone	UBERON:0003053	97.24	gold quality
right uterine tube	UBERON:0001302	97.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.95	gold quality
sural nerve	UBERON:0015488	96.79	gold quality
colonic epithelium	UBERON:0000397	96.67	gold quality
epithelium of nasopharynx	UBERON:0001951	96.34	gold quality
nasopharynx	UBERON:0001728	96.32	gold quality
tendon	UBERON:0000043	96.21	gold quality
stromal cell of endometrium	CL:0002255	96.08	gold quality
right lobe of liver	UBERON:0001114	95.77	gold quality
lower esophagus mucosa	UBERON:0035834	95.74	gold quality
ganglionic eminence	UBERON:0004023	95.72	gold quality
body of pancreas	UBERON:0001150	95.64	gold quality
right lung	UBERON:0002167	95.50	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.33	gold quality
right adrenal gland cortex	UBERON:0035827	95.33	gold quality
right adrenal gland	UBERON:0001233	94.35	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.30	gold quality
left adrenal gland	UBERON:0001234	94.22	gold quality
left adrenal gland cortex	UBERON:0035825	94.17	gold quality
nerve	UBERON:0001021	94.11	gold quality
tibial nerve	UBERON:0001323	94.11	gold quality
adrenal gland	UBERON:0002369	94.05	gold quality
adrenal cortex	UBERON:0001235	94.00	gold quality
tonsil	UBERON:0002372	93.96	gold quality
upper lobe of left lung	UBERON:0008952	93.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.86	gold quality
vagina	UBERON:0000996	93.85	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	2243.14
E-MTAB-7051	yes	1827.48
E-GEOD-98556	yes	1721.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
DNMT3A	Activation
PIK3R1	Unknown

Upstream regulators (CollecTRI, top): AHR, AP1, AR, BCL11B, BCL3, BRCA1, CDKN2AIP, CREB1, CTNNBL1, DDIT3, DNMT1, E2F1, E2F2, EGR1, ELF4, ELL, EP300, ESR1, ETS1, ETS2, EWSR1, FEZF2, FLI1, FOS, FOSL2, FOXC1, FUS, GATA3, HES1, HEY1, HIF1A, HMGB2, HNF4A, HR, IRF8, JUN, JUND, LITAF, MLLT10, MLLT3

miRNA regulators (miRDB)

169 targeting MDM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-551B-5P	99.96	71.28	3493

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 38.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• evidence for distinct biological function of Trx-1 (PMID:11877442)
• dimer dissociation constants K(d) were found to be 2.2mM for reduced DmTrx and above 10mM for oxidized DmTrx as well as for the protein in the presence of reduced glutathione (PMID:15644209)
• Drosophila thioredoxin can function as an anti-aging agent and as a suppressor of Parkin-associated endothelin receptor-like receptor - and poly-glutamine-induced neurotoxicity (PMID:17301052)
• This study demonstrates that DHD localizes to the sperm nucleus to reduce its disulfide targets and is then rapidly degraded after fertilization. (PMID:27876811)
• thioredoxin DHD plays a critical role in early development to facilitate the switch from protamine-based sperm chromatin structures to the somatic nucleosomal chromatin. (PMID:28031247)
• Three classes of epigenomic regulators converge to hyperactivate the essential maternal gene deadhead within a heterochromatin mini-domain. (PMID:34982772)
• mdm2 has binding sites for phosphorylation by CK2 (PMID:10561590)
• protein interaction mapping with mouse p19ARF (PMID:11718560)
• a regulatory loop exists in which Hdm2 regulates the intracellular localization of Hdmx, and nuclear Hdmx regulates several functions of Hdm2 (ubiquitin ligase activity and p53 nuclear export). (PMID:11744695)
• higher expression in childhood leukemias with poor prognosis compared to long-term survivors (PMID:11764099)
• Normal cells may induce full-length MDM2 in response to oncogenic challenges to protect against premature cell cycle progression. MDM2 is regulated by p53 especially durnig embryogenesis where MDM2 function is inhibited. (PMID:11779693)
• findings suggest that amplification and overexpression of HMGIC and possibly MDM2 might be important genetic events that may contribute to malignant transformation of benign pleomorphic adenoma (PMID:11839563)
• absence of nucleolar or nucleoplasmic p14ARF/Hdm2 complexes in Reed Sternberg cells in Hodgkin’s lymphoma associated with expression of alternatively spliced Hdm2 transcripts (PMID:11839577)
• MDM2 overexpression correlates with favorable prognosis in human breast cancer (PMID:11859876)
• p53 ativation by nitric oxide involves down-regulation (PMID:11867628)
• role for IGF-I in the regulation of the MDM2/p53/p21 signaling pathway during DNA damage (PMID:11877395)
• Antisense of MDM2 enhance therapeutic efficiency of irinotecan in colon cancer (PMID:11894120)
• Akt enhances Mdm2-mediated ubiquitination and degradation of p53. (PMID:11923280)
• description of a novel MDM2 binding interface in p53 that plays a regulatory role in MDM2-dependent ubiquitination of p53 (PMID:11925449)
• Novel splice variants identified in pediatric rhabdomyosarcoma tumors and cell lines (PMID:11939408)
• MDMX, when exceedingly overexpressed, inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding (PMID:11953423)
• Cirrhotic livers reveal genetic changes in the MDM2-P14ARF system of cell cycle regulators. (PMID:11953887)
• promoter usage of mdm2 gene in human breast cancer (PMID:11956627)
• Phosphorylation of HDM2 by Akt, and protein binding (PMID:11960368)
• summarize the current understanding of post-translational modifications and their effect on conformation-based functional relationship between Mdm2 and p53 (PMID:11960904)
• MDM2 induces NF-kappaB/p65 expression transcriptionally through Sp1-binding sites; a novel, p53-independent role of MDM2 in doxorubicin resistance in acute lymphoblastic leukemia. (PMID:11964305)
• Cyclin G expression also results in reduced phosphorylation of human Hdm2 at S166. (PMID:11983168)
• p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products. (PMID:12032546)
• expression significantly correlated with favorable prognosis in esophageal squamous cell carcinoma in p53-negative patients but not p53-positive patients (PMID:12052755)
• MDM2 can inhibit PCAF-mediated p53 acetylation and activation. (PMID:12068014)
• MDM2 inhibition of p53 induces E2F1 transactivation via p21 (PMID:12080472)
• RNA polymerase III transcription can be derepressed by hdm2 (PMID:12082526)
• Multiple interacting domains contribute to p14ARF mediated inhibition of MDM2 (PMID:12085228)
• implications of phosphorylation in p53 regulation (PMID:12110584)
• Data suggest a model in which p53 directly recruits a TRRAP/acetyltransferase complex to the mdm2 gene to activate transcription. In addition, this study defines a novel mechanism utilized by the p53 tumor suppressor to regulate gene expression. (PMID:12138177)
• MDM2 has been characterized as a protein that binds to and facilitates degradation of the tumor suppressor p53. Splice variants of MDM2 transcripts have been identified in both tumors and normal tissues. (PMID:12150820)
• Hypophosphorylation of Mdm2 augments p53 stability. The degree of conservation in the central acidic domain of mouse and human Mdm2 proteins is high. (PMID:12167711)
• The candidate tumor suppressor ING1b can stabilize p53 by disrupting the regulation of p53 by MDM2. (PMID:12208736)
• MAPK as an upstream regulator of mdm2 expression (PMID:12231395)
• MDM2 is not required for p53 proteasomal degradation regulated by NADPH quinone oxidoreductase 1 (PMID:12232053)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mdm2	ENSDARG00000033443
mus_musculus	Mdm2	ENSMUSG00000020184
rattus_norvegicus	Mdm2	ENSRNOG00000006304

Paralogs (1): MDM4 (ENSG00000198625)

Protein

Protein identifiers

E3 ubiquitin-protein ligase Mdm2 — Q00987 (reviewed: Q00987)

Alternative names: Double minute 2 protein, Oncoprotein Mdm2, RING-type E3 ubiquitin transferase Mdm2, p53-binding protein Mdm2

All UniProt accessions (23): A0A0A8K986, A0A0A8KB88, Q00987, A0A0A8KBA1, A0A0C4DFR5, A0A1B0GXJ6, A7UKX8, E5RHE2, E5RJQ0, E7EMW5, E7EPE2, F5GWH7, F5GZB0, F5GZC3, F5H1M7, F5H4Q8, F6UXB6, G3XA89, J3KN53, J3QST1, Q96DS5, Q9H4C3, Q9H4C5

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. 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. 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. Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis. 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.

Subunit / interactions. Component of a ternary complex composed of FAM193A, MDM4 and MDM2; interaction of FAM193A with MDM4 is mediated by the MDM4 RING-type zinc finger and results in MDM4 destabilization, leading to enhanced p53/TP53 transcriptional activity. Although FAM193A interacts with MDM4 and MDM2, it does not affect formation of the p53-MDM2-MDM4 transcriptional repressor complex. Interacts with p53/TP53, TP73/p73, RBL5 and RP11. Binds specifically to RNA. Can interact with RB1, E1A-associated protein EP300 and the E2F1 transcription factor. Forms a ternary complex with p53/TP53 and WWOX. Interacts with CDKN2AIP, RFWD3, USP7, PYHIN1, and RBBP6. Interacts with ARRB1 and ARRB2. Interacts with PSMA3. Found in a trimeric complex with MDM2, MDM4 and USP2. Interacts with USP2 (via N-terminus and C-terminus). Interacts with MDM4. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts directly with DAXX and USP7. Interacts (via C-terminus) with RASSF1 isoform A (via N-terminus); the interaction is independent of TP53. Interacts with APEX1; leading to its ubiquitination and degradation. Interacts with RYBP; this inhibits ubiquitination of TP53. Identified in a complex with RYBP and p53/TP53. Also a component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in regulating p53/TP53 stabilization and activity. Binds directly both p53/TP53 and TRIM28. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor responses with DNA damage. Interacts directly with both TRIM28 and ERBB4 in the complex. Interacts with DYRK2. Interacts with IGF1R. Interacts with TRIM13; the interaction ubiquitinates MDM2 leading to its proteasomal degradation. Interacts with SNAI1; this interaction promotes SNAI1 ubiquitination. Interacts with NOTCH1 (via intracellular domain). Interacts with FHIT. Interacts with RFFL and RNF34; the interaction stabilizes MDM2. Interacts with CDK5RAP3 and CDKN2A/ARF; form a ternary complex involved in regulation of p53/TP53. Interacts with MTA1. Interacts with AARB2. Interacts with MTBP. Interacts with PML. Interacts with TBRG1. Interacts (via its RanBP2-type zinc finger domain) with RPL11 in the 5S RNP complex composed of 5S RNA, RPL5 and RPL11; this interaction occurs in the nucleoplasm and negatively regulates MDM2-mediated TP53 ubiquitination and degradation. Interacts with ADGRB1; the interaction results in inhibition of MDM2-mediated ubiquitination and degradation of DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity. Interacts with RPL23A; this interaction may promote p53/TP53 polyubiquitination. Interacts with NDUFS1. Interacts with MORN3; the interaction enhances the ubiquitination of p53/TP53. Interacts with RAD54B; RAD54B enhances the ubiquitin ligase activity of MDM2 on TP53 by promoting MDM2-MDM4 heterodimerization. (Microbial infection) Interacts with herpes virus 8 protein v-IRF4. (Microbial infection) Interacts with and ubiquitinates HIV-1 Tat.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm. Nucleolus.

Tissue specificity. Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform Mdm2-G are observed in a range of cancers but absent in normal tissues.

Post-translational modifications. Phosphorylation on Ser-166 by SGK1 activates ubiquitination of p53/TP53. Phosphorylated at multiple sites near the RING domain by ATM upon DNA damage; this promotes its ubiquitination and degradation, preventing p53/TP53 degradation. Autoubiquitination leads to proteasomal degradation; resulting in p53/TP53 activation it may be regulated by SFN. Also ubiquitinated by TRIM13. ATM-phosphorylated MDM2 is ubiquitinated by the SCF(FBXO31) complex in response to genotoxic stress, promoting its degradation and p53/TP53-mediated DNA damage response. Deubiquitinated by USP2 leads to its accumulation and increases deubiquitination and degradation of p53/TP53. Deubiquitinated by USP7 leading to its stabilization.

Disease relevance. Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding. Lessel-Kubisch syndrome (LSKB) [MIM:618681] An autosomal recessive progeroid syndrome characterized by short stature, pinched facial features, prematurely gray hair, scleroderma-like skin changes, small kidneys and consecutive kidney failure, followed by severe arterial hypertension. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself.

Induction. By DNA damage.

Polymorphism. A polymorphism in the MDM2 promoter is associated with susceptibility to accelerated tumor formation in both hereditary and sporadic cancers [MIM:614401]. It also contributes to susceptibility to Li-Fraumeni syndrome, in patients carrying a TP53 germline mutation.

Miscellaneous. MDM2 RING finger mutations that failed to ubiquitinate p53 in vitro did not target p53 for degradation when expressed in cells. Does not interact with p53/TP53.

Similarity. Belongs to the MDM2/MDM4 family.

Isoforms (11)

UniProt ID	Names	Canonical?
Q00987-1	Mdm2	yes
Q00987-2	Mdm2-A
Q00987-3	Mdm2-A1
Q00987-4	Mdm2-B
Q00987-5	Mdm2-C
Q00987-6	Mdm2-D
Q00987-7	Mdm2-E
Q00987-8	Mdm2-alpha
Q00987-9	Mdm2-F
Q00987-10	Mdm2-G
Q00987-11	11

RefSeq proteins (6): NP_001138809, NP_001138811, NP_001138812, NP_001265391, NP_001354919, NP_002383* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR001876	Znf_RanBP2	Domain
IPR003121	SWIB_MDM2_domain	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR016495	p53_neg-reg_MDM_2/4	Family
IPR028340	Mdm2	Family
IPR036443	Znf_RanBP2_sf	Homologous_superfamily
IPR036885	SWIB_MDM2_dom_sf	Homologous_superfamily
IPR044080	MDM2_mRING-HC-C2H2C4	Domain

Pfam: PF00641, PF02201, PF13920

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (103 total): mutagenesis site 21, strand 16, region of interest 13, modified residue 13, splice variant 11, helix 8, turn 6, binding site 4, short sequence motif 3, compositionally biased region 3, zinc finger region 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

147 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6Q9L	X-RAY DIFFRACTION	1.13
5C5A	X-RAY DIFFRACTION	1.15
6Q9O	X-RAY DIFFRACTION	1.21
5ZXF	X-RAY DIFFRACTION	1.25
7QDQ	X-RAY DIFFRACTION	1.26
8F10	X-RAY DIFFRACTION	1.28
8P0D	X-RAY DIFFRACTION	1.31
5Z02	X-RAY DIFFRACTION	1.35
8J81	X-RAY DIFFRACTION	1.35
4OGN	X-RAY DIFFRACTION	1.38
2AXI	X-RAY DIFFRACTION	1.4
7KJM	X-RAY DIFFRACTION	1.4
8F13	X-RAY DIFFRACTION	1.4
6SQO	X-RAY DIFFRACTION	1.41
4WT2	X-RAY DIFFRACTION	1.42
4UE1	X-RAY DIFFRACTION	1.45
7NUS	X-RAY DIFFRACTION	1.45
8PWC	X-RAY DIFFRACTION	1.46
8GCG	X-RAY DIFFRACTION	1.47
4OGT	X-RAY DIFFRACTION	1.54
7AI0	X-RAY DIFFRACTION	1.56
5OC8	X-RAY DIFFRACTION	1.56
5LN2	X-RAY DIFFRACTION	1.58
7BJ6	X-RAY DIFFRACTION	1.59
3LBL	X-RAY DIFFRACTION	1.6
4HG7	X-RAY DIFFRACTION	1.6
4UD7	X-RAY DIFFRACTION	1.6
4OBA	X-RAY DIFFRACTION	1.6
3TU1	X-RAY DIFFRACTION	1.6
8F0Z	X-RAY DIFFRACTION	1.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00987-F1	63.24	0.30

Antibody-complex structures (SAbDab): 1 — 5WTS

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 305; 308; 319; 322

Post-translational modifications (13): 166, 190, 240, 242, 246, 260, 262, 386, 395, 407, 419, 425, 429

Mutagenesis-validated functional residues (21):

Position	Phenotype
58	no effect on its ability to induce apoptosis.
305	no loss of ubiquitin ligase e3 activity.
374	no loss of ubiquitin ligase e3 activity.
386	in mdm2-6a mutant; abolished phosphorylation by atm and ubiquitination by the scf(fbxo31) complex; when associated with
395	in mdm2-6a mutant; abolished phosphorylation by atm and ubiquitination by the scf(fbxo31) complex; when associated with
407	in mdm2-6a mutant; abolished phosphorylation by atm and ubiquitination by the scf(fbxo31) complex; when associated with
419	in mdm2-6a mutant; abolished phosphorylation by atm and ubiquitination by the scf(fbxo31) complex; when associated with
425	in mdm2-6a mutant; abolished phosphorylation by atm and ubiquitination by the scf(fbxo31) complex; when associated with
429	in mdm2-6a mutant; abolished phosphorylation by atm and ubiquitination by the scf(fbxo31) complex; when associated with
438	no loss of ubiquitin ligase e3 activity.
441	fails to interact with mdm4.
449	loss of ubiquitin ligase e3 activity.
449	no substantial decrease of ubiquitin ligase e3 activity.
452	loss of ubiquitin ligase e3 activity.
455	significant decrease of ubiquitin ligase e3 activity.
457	loss of ubiquitin ligase e3 activity.
461	loss of ubiquitin ligase e3 activity.
464	loss of ubiquitin ligase e3 activity, enhances protein stability. does not inhibit interaction with apex1, but inhibits
475	loss of ubiquitin ligase e3 activity.
478	fails to interact with mdm4.
478	loss of ubiquitin ligase e3 activity.

Function

Pathways and Gene Ontology

Reactome pathways

48 pathways

ID	Pathway
R-HSA-198323	AKT phosphorylates targets in the cytosol
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-5689880	Ub-specific processing proteases
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-6804760	Regulation of TP53 Activity through Methylation
R-HSA-69541	Stabilization of p53
R-HSA-8941858	Regulation of RUNX3 expression and activity
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-9766229	Degradation of CDH1
R-HSA-9768919	NPAS4 regulates expression of target genes
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-3700989	Transcriptional Regulation by TP53

MSigDB gene sets: 743 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, MODULE_97, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, BROWNE_HCMV_INFECTION_6HR_DN, MORF_FLT1, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, BIOCARTA_ATM_PATHWAY, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, HOFMANN_CELL_LYMPHOMA_UP

GO Biological Process (74): negative regulation of transcription by RNA polymerase II (GO:0000122), protein polyubiquitination (GO:0000209), blood vessel development (GO:0001568), blood vessel remodeling (GO:0001974), regulation of heart rate (GO:0002027), atrioventricular valve morphogenesis (GO:0003181), endocardial cushion morphogenesis (GO:0003203), ventricular septum development (GO:0003281), atrial septum development (GO:0003283), ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), traversing start control point of mitotic cell cycle (GO:0007089), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), response to toxic substance (GO:0009636), response to iron ion (GO:0010039), positive regulation of gene expression (GO:0010628), negative regulation of protein processing (GO:0010955), negative regulation of neuron projection development (GO:0010977), protein ubiquitination (GO:0016567), protein sumoylation (GO:0016925), DNA damage response, signal transduction by p53 class mediator (GO:0030330), protein destabilization (GO:0031648), response to magnesium ion (GO:0032026), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), protein localization to nucleus (GO:0034504), regulation of protein catabolic process (GO:0042176), response to cocaine (GO:0042220), negative regulation of apoptotic process (GO:0043066), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043518), establishment of protein localization (GO:0045184), response to ether (GO:0045472), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of mitotic cell cycle (GO:0045931), response to antibiotic (GO:0046677), positive regulation of protein export from nucleus (GO:0046827), response to steroid hormone (GO:0048545), positive regulation of muscle cell differentiation (GO:0051149), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (20): p53 binding (GO:0002039), ubiquitin-protein transferase activity (GO:0004842), 5S rRNA binding (GO:0008097), zinc ion binding (GO:0008270), ligase activity (GO:0016874), SUMO transferase activity (GO:0019789), enzyme binding (GO:0019899), protein domain specific binding (GO:0019904), ubiquitin protein ligase binding (GO:0031625), receptor serine/threonine kinase binding (GO:0033612), identical protein binding (GO:0042802), peroxisome proliferator activated receptor binding (GO:0042975), ribonucleoprotein complex binding (GO:0043021), ubiquitin binding (GO:0043130), ubiquitin protein ligase activity (GO:0061630), NEDD8 ligase activity (GO:0061663), disordered domain specific binding (GO:0097718), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (16): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), transcription repressor complex (GO:0017053), endocytic vesicle membrane (GO:0030666), protein-containing complex (GO:0032991), centriolar satellite (GO:0034451), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), glutamatergic synapse (GO:0098978), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Cellular Senescence	2
SUMO E3 ligases SUMOylate target proteins	2
Regulation of TP53 Activity	2
PIP3 activates AKT signaling	1
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
PI3K/AKT Signaling in Cancer	1
Deubiquitination	1
Regulation of TP53 Expression and Degradation	1
p53-Dependent G1 DNA Damage Response	1
Transcriptional regulation by RUNX3	1
Signaling by ALK in cancer	1
Regulation of CDH1 Function	1
Transcriptional Regulation by NPAS4	1
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
protein binding	4
sperm flagellum	3
protein ubiquitination	2
cardiac septum development	2
response to chemical	2
ubiquitin-like protein transferase activity	2
catalytic activity	2
signaling receptor binding	2
ubiquitin-like protein ligase activity	2
nuclear lumen	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
vasculature development	1
anatomical structure development	1
tissue remodeling	1
regulation of heart contraction	1
regulation of biological quality	1
atrioventricular valve development	1
heart valve morphogenesis	1
heart morphogenesis	1
endocardial cushion development	1
mesenchyme morphogenesis	1
cardiac ventricle development	1
cardiac atrium development	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
positive regulation of G1/S transition of mitotic cell cycle	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to metal ion	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
protein processing	1

Protein interactions and networks

STRING

6454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MDM2	TP53	P04637	999
MDM2	CDKN2A	P42771	999
MDM2	RPL11	P25121	997
MDM2	TCHP	Q9BT92	997
MDM2	RPL5	P46777	996
MDM2	USP7	Q93009	995
MDM2	EP300	Q09472	994
MDM2	NUMBL	Q9Y6R0	992
MDM2	NUMB	P49757	990
MDM2	MDM4	O15151	986
MDM2	FOXO3	O43524	983
MDM2	E2F1	Q01094	981
MDM2	AR	P10275	980
MDM2	AKT1	P31749	980
MDM2	RPL26	P61254	971

IntAct

725 interactions, top by confidence:

A	B	Type	Score
TP53	MDM2	psi-mi:“MI:0915”(physical association)	1.000
MDM2	TP53	psi-mi:“MI:0914”(association)	1.000
MDM2	TP53	psi-mi:“MI:0915”(physical association)	1.000
MDM2	TP53	psi-mi:“MI:0407”(direct interaction)	1.000
TP53	MDM2	psi-mi:“MI:0407”(direct interaction)	1.000
TP53	MDM2	psi-mi:“MI:0914”(association)	1.000

BioGRID (2713): MDM2 (Affinity Capture-Western), TP53 (Reconstituted Complex), RCHY1 (Reconstituted Complex), MDM2 (Reconstituted Complex), MDM2 (Affinity Capture-Western), MDM2 (Affinity Capture-Western), AATF (Affinity Capture-Western), MDM2 (Affinity Capture-Western), TP53 (Biochemical Activity), MDM2 (Affinity Capture-Western), MDM2 (Affinity Capture-Western), MDM2 (Reconstituted Complex), PML (Affinity Capture-Western), RPL23 (Affinity Capture-Western), RPL26 (Affinity Capture-Western)

ESM2 similar proteins: A2VCV0, A6H8Z2, A8T6P4, C3VD30, F6QRE9, P23497, P23804, P56950, Q00987, Q0P6D6, Q13342, Q1XFL1, Q32MH5, Q4JF29, Q5BLK4, Q5PQX1, Q5VYS8, Q5ZI58, Q60524, Q62187, Q66HD8, Q68FE6, Q69ZK7, Q6DRC5, Q6IE24, Q6NYJ3, Q6P752, Q6PCX9, Q70EL1, Q76N89, Q7L190, Q7T3T8, Q7T3T9, Q7YRZ8, Q7ZUW7, Q80UF7, Q8BL06, Q8BYU6, Q8C627, Q8C9M2

Diamond homologs: B3H754, F4ISV9, O15151, O35618, P23804, P56273, P56950, P56951, Q00987, Q0WS06, Q2HJ21, Q5XIN1, Q60524, Q6DBH0, Q7YRZ8, Q7ZUW7, Q7ZYI3, O42354, Q84ME1, Q8LA32, Q9LFH6, Q9LYW5, M0R5D6, O10296, O60291, P41435, P97587, Q3TEL6, Q5M7X9, Q5M870, Q5XIQ4, Q6INH1, Q6R7I2, Q7M3S9, Q7ZUL9, Q8BMJ7, Q8BUH7, Q8CJC5, Q94HV7, Q96PX1

SIGNOR signaling

127 interactions.

A	Effect	B	Mechanism
ATM	“down-regulates activity”	MDM2	phosphorylation
AKT2	“up-regulates quantity by stabilization”	MDM2	phosphorylation
AKT2	“up-regulates activity”	MDM2	phosphorylation
AKT1	“up-regulates quantity by stabilization”	MDM2	phosphorylation
AKT1	“up-regulates activity”	MDM2	phosphorylation
ATR	“down-regulates activity”	MDM2	phosphorylation
DAPK3	“up-regulates quantity by stabilization”	MDM2	phosphorylation
AKT1	up-regulates	MDM2	phosphorylation
FHIT	down-regulates	MDM2
MAPKAPK2	“up-regulates quantity by stabilization”	MDM2	phosphorylation
MDM4	“up-regulates quantity by stabilization”	MDM2
USP7	up-regulates	MDM2	deubiquitination
BCL3	“up-regulates quantity by expression”	MDM2	“transcriptional regulation”
MDM2	down-regulates	MDM4	ubiquitination
PPM1D	up-regulates	MDM2	dephosphorylation
CDKN2AIP	“down-regulates quantity by repression”	MDM2	“transcriptional regulation”
MDM2	down-regulates	CDKN2AIP	ubiquitination
MDM2	“down-regulates quantity by repression”	CDKN1A
CSNK1D	down-regulates	MDM2	phosphorylation
NfKb-p65/p50	“up-regulates quantity by expression”	MDM2	“transcriptional regulation”
NUMB	down-regulates	MDM2	binding
ABL1	down-regulates	MDM2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Degradation	6	33.8×	1e-05
Oncogene Induced Senescence	5	32.3×	1e-04
Peptide chain elongation	6	14.6×	4e-04
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	6	13.6×	5e-04
Viral mRNA Translation	5	12.2×	2e-03
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	5	12.1×	2e-03
SRP-dependent cotranslational protein targeting to membrane	6	11.6×	9e-04
Selenocysteine synthesis	5	11.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	14.9×	4e-03
regulation of apoptotic process	6	8.1×	6e-03
protein stabilization	7	7.5×	4e-03
regulation of cell cycle	6	7.2×	9e-03
negative regulation of cell population proliferation	9	6.1×	4e-03
negative regulation of apoptotic process	10	5.6×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — LMS.

Clinical variants and AI predictions

ClinVar

174 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	96
Likely benign	56
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
694663	NM_002392.6(MDM2):c.1492T>C (p.Ter498Gln)	Likely pathogenic

SpliceAI

2366 predictions. Top by Δscore:

Variant	Effect	Δscore
12:68809203:T:TA	acceptor_gain	1.0000
12:68809204:GTA:G	acceptor_loss	1.0000
12:68809206:A:AG	acceptor_gain	1.0000
12:68809206:AG:A	acceptor_gain	1.0000
12:68809207:G:GC	acceptor_gain	1.0000
12:68809207:GG:G	acceptor_gain	1.0000
12:68809207:GGC:G	acceptor_gain	1.0000
12:68809207:GGCA:G	acceptor_gain	1.0000
12:68809207:GGCAA:G	acceptor_gain	1.0000
12:68809291:TG:T	donor_gain	1.0000
12:68809292:GG:G	donor_gain	1.0000
12:68809293:G:A	donor_loss	1.0000
12:68809293:G:GG	donor_gain	1.0000
12:68820315:T:A	acceptor_gain	1.0000
12:68824361:A:AG	acceptor_gain	1.0000
12:68824362:G:GG	acceptor_gain	1.0000
12:68824362:GA:G	acceptor_gain	1.0000
12:68824362:GAATC:G	acceptor_gain	1.0000
12:68824545:A:AG	acceptor_gain	1.0000
12:68824545:AAAT:A	acceptor_gain	1.0000
12:68824546:A:G	acceptor_gain	1.0000
12:68824548:T:G	acceptor_gain	1.0000
12:68824551:TTAGG:T	acceptor_loss	1.0000
12:68824553:AGGAC:A	acceptor_loss	1.0000
12:68824554:G:A	acceptor_loss	1.0000
12:68824650:AG:A	donor_loss	1.0000
12:68824651:GG:G	donor_loss	1.0000
12:68824652:G:GA	donor_loss	1.0000
12:68824653:T:A	donor_loss	1.0000
12:68828763:A:AG	acceptor_gain	1.0000

AlphaMissense

3295 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:68839685:T:C	C438R	1.000
12:68839694:T:C	C441R	1.000
12:68839725:T:A	V451D	1.000
12:68839754:T:C	C461R	1.000
12:68839763:T:C	C464R	1.000
12:68839765:T:G	C464W	1.000
12:68839776:T:C	L468P	1.000
12:68839796:T:C	C475R	1.000
12:68839805:T:C	C478R	1.000
12:68813561:C:A	P30Q	0.999
12:68813585:T:C	L38S	0.999
12:68816837:T:A	I61N	0.999
12:68816852:T:C	L66S	0.999
12:68816879:T:A	V75E	0.999
12:68816886:T:G	C77W	0.999
12:68816927:T:C	F91S	0.999
12:68839685:T:A	C438S	0.999
12:68839686:G:A	C438Y	0.999
12:68839686:G:C	C438S	0.999
12:68839687:T:G	C438W	0.999
12:68839694:T:A	C441S	0.999
12:68839695:G:A	C441Y	0.999
12:68839695:G:C	C441S	0.999
12:68839696:T:G	C441W	0.999
12:68839716:G:A	G448D	0.999
12:68839729:T:A	H452Q	0.999
12:68839729:T:G	H452Q	0.999
12:68839740:G:A	G456E	0.999
12:68839742:C:G	H457D	0.999
12:68839744:T:A	H457Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000065196 (12:68844417 T>G), RS1000066442 (12:68814955 A>G), RS1000091227 (12:68845383 T>C,G), RS1000101667 (12:68821490 A>C), RS1000116675 (12:68814633 A>G), RS1000225981 (12:68833497 A>C,T), RS1000273365 (12:68839128 C>T), RS1000330806 (12:68827282 C>G), RS1000374492 (12:68815418 G>A), RS1000468493 (12:68832735 T>C), RS1000492267 (12:68848490 C>T), RS1000493574 (12:68833480 G>C), RS1000496640 (12:68810441 T>C), RS1000544105 (12:68848736 G>A), RS1000573624 (12:68851174 A>C,T)

Disease associations

OMIM: gene MIM:164785 | disease phenotypes: MIM:618681

GenCC curated gene-disease

Disease	Classification	Inheritance
Li-Fraumeni syndrome	Supportive	Autosomal dominant
lessel-kubisch syndrome	Limited	Unknown

Mondo (2): lessel-kubisch syndrome (MONDO:0032868), Li-Fraumeni syndrome (MONDO:0018875)

Orphanet (0):

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000135	Hypogonadism
HP:0000160	Narrow mouth
HP:0000446	Narrow nasal bridge
HP:0000822	Hypertension
HP:0001482	Subcutaneous nodule
HP:0001620	Abnormally high-pitched voice
HP:0001909	Leukemia
HP:0002216	Premature graying of hair
HP:0002225	Sparse pubic hair
HP:0002579	Gastrointestinal dysmotility
HP:0002664	Neoplasm
HP:0002665	Lymphoma
HP:0002669	Osteosarcoma
HP:0002859	Rhabdomyosarcoma
HP:0002861	Melanoma
HP:0002863	Myelodysplasia
HP:0002885	Medulloblastoma
HP:0002888	Ependymoma
HP:0002890	Thyroid carcinoma
HP:0002894	Neoplasm of the pancreas
HP:0003002	Breast carcinoma
HP:0003003	Colon cancer
HP:0004322	Short stature
HP:0004808	Acute myeloid leukemia
HP:0006721	Acute lymphoblastic leukemia
HP:0006744	Adrenocortical carcinoma
HP:0007378	Neoplasm of the gastrointestinal tract

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002515_1	Pneumoconiosis in silica exposure	2.000000e-08
GCST90002403_454	Red blood cell count	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016864	Li-Fraumeni Syndrome	C04.700.600; C16.320.700.600; C18.452.284.520

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (16): CHEMBL1907611 (PROTEIN-PROTEIN INTERACTION), CHEMBL3038493 (PROTEIN COMPLEX), CHEMBL3883306 (PROTEIN-PROTEIN INTERACTION), CHEMBL4106123 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523702 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523718 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523719 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523720 (PROTEIN-PROTEIN INTERACTION), CHEMBL4879538 (PROTEIN-PROTEIN INTERACTION), CHEMBL4888446 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 341,740 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL572	NITROFURANTOIN	4	26,231
CHEMBL53	APOMORPHINE	4	25,813
CHEMBL803	CYTARABINE	4	202,889
CHEMBL2402737	IDASANUTLIN	3	1,511
CHEMBL3125702	NAVTEMADLIN	3	1,107
CHEMBL4292264	MILADEMETAN	3	466
CHEMBL5314455	BRIGIMADLIN	3	10
CHEMBL120563	THIRAM	2	79,340
CHEMBL3653256	SIREMADLIN	2	1,320
CHEMBL4091801	ALRIZOMADLIN	2	556
CHEMBL2381408	SAR-405838	1	547
CHEMBL3128043	PF-03758309	1	233
CHEMBL3601398	CGM-097	1	921
CHEMBL2386346	RO-5045337	1	796

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 3 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
MDM2 EXPRESSION	Pemetrexed + Cisplatin	Malignant Pleural Mesothelioma	Resistance	CIViC B	EID827
MDM2 EXPRESSION	Navtemadlin	Ovarian Cancer	Sensitivity/Response	CIViC D	EID9852

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1690924	Efficacy	3	Platinum compounds	Non-Small Cell Lung Carcinoma

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1690924	MDM2	3	2.00	1	Platinum compounds
rs2279744	MDM2		0.00	0
rs1470383	MDM2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — E3 ubiquitin ligase components

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
navtemadlin	Inhibition	10.35	pKd
JN122	Binding	9.15	pKi
milademetan	Binding	8.25	pIC50

Binding affinities (BindingDB)

3565 measured of 3818 human assays (3829 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(2-chlorophenyl)-5-(dimethylamino)-1,3-oxazole-4-carbonitrile	EC50	0.00186 nM
(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-[5-(hydroxymethyl)-2-methoxyphenyl]-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.04 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-N-(2-hydroxyethyl)-4-methoxybenzamide	IC50	0.05 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
(4S)-5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-4-(4-chlorophenyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-3-[(2R)-1-methoxypropan-2-yl]-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.059 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
2-[3-[(6S)-5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxyphenyl]acetic acid	IC50	0.061 nM	US-9365576: Pyrrolopyrrolidinone compounds
(6S)-5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-4-one	IC50	0.065 nM	US-9365576: Pyrrolopyrrolidinone compounds
(4S)-5-(5-chloro-2-oxopiperidin-3-yl)-4-(4-chlorophenyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.068 nM	US-8969341: Pyrazolopyrrolidine compounds
5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-4-one	IC50	0.068 nM	US-9365576: Pyrrolopyrrolidinone compounds
4-[(6S)-5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-6-yl]benzonitrile	IC50	0.069 nM	US-9365576: Pyrrolopyrrolidinone compounds
3-[4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxy-N,N-dimethylbenzamide	IC50	0.07 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
N-[[3-[4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxyphenyl]methyl]acetamide	IC50	0.07 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.07 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
(6S)-6-(4-chloro-3-fluorophenyl)-5-(5-chloro-2-oxopiperidin-3-yl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-4-one	IC50	0.071 nM	US-9365576: Pyrrolopyrrolidinone compounds
3-[(6S)-5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-N,N-dimethylbenzamide	IC50	0.075 nM	US-9365576: Pyrrolopyrrolidinone compounds
(6S)-2-(2-amino-4-methoxypyrimidin-5-yl)-5-(3-chloro-4-fluorophenyl)-6-(4-chlorophenyl)-1-[(2R)-1-methoxypropan-2-yl]-6H-pyrrolo[3,4-b]pyrrol-4-one	IC50	0.078 nM	US-9365576: Pyrrolopyrrolidinone compounds
(6S)-5-(3-chloro-2-oxo-3H-pyridin-5-yl)-6-(4-chlorophenyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-4-one	IC50	0.079 nM	US-9365576: Pyrrolopyrrolidinone compounds
3-[5-(3-chloro-4-fluorophenyl)-4-(4-chlorophenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxybenzamide	IC50	0.08 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxy-N-propan-2-ylbenzamide	IC50	0.08 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
N-[[3-[4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxyphenyl]methyl]-2-hydroxyacetamide	IC50	0.08 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
4-[5-(3-chloro-2-fluorophenyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-4-yl]-2-fluorobenzonitrile	IC50	0.08 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[(6S)-5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxybenzoic acid	IC50	0.08 nM	US-9365576: Pyrrolopyrrolidinone compounds
(4S)-5-(5-chloro-1-methyl-2-oxo-3-pyridinyl)-4-(4-chlorophenyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.081 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
(6S)-5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-6-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-4-one	IC50	0.087 nM	US-9365576: Pyrrolopyrrolidinone compounds
(4S)-5-(3-chloro-4-fluorophenyl)-4-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-[(2R)-1-methoxypropan-2-yl]-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.089 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
2-[5-(aminomethyl)-2-methoxyphenyl]-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.09 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
5-(5-chloro-2-methylphenyl)-4-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-[(2R)-1-hydroxypropan-2-yl]-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.09 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[5-(5-chloro-2-methylphenyl)-4-(4-chlorophenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxy-N-propan-2-ylbenzamide	IC50	0.09 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxy-N,N-dimethylbenzamide	IC50	0.09 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[(6S)-6-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-N-methylbenzamide	IC50	0.094 nM	US-9365576: Pyrrolopyrrolidinone compounds
3-[(6S)-5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-N-methylbenzamide	IC50	0.095 nM	US-9365576: Pyrrolopyrrolidinone compounds
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	IC50	0.0962 nM	US-8952036: Benzoic acid derivative MDM2 inhibitor for the treatment of cancer
4-[(4S)-5-(5-chloro-2-oxopiperidin-3-yl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-4-yl]benzonitrile	IC50	0.097 nM	US-8969341: Pyrazolopyrrolidine compounds
(4S)-5-(5-chloro-2-oxo-1H-pyridin-3-yl)-4-(4-chlorophenyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.1 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[5-(5-chloro-2-methylphenyl)-4-(4-chlorophenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-2-yl]-4-methoxybenzamide	IC50	0.1 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-[difluoromethyl(ethylsulfonyl)amino]ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-[cyclopropylsulfonyl(difluoromethyl)amino]ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(N-ethylsulfonyl-2-fluoroanilino)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9296736: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-[(2S)-1-[(3-methyloxetan-3-yl)methylsulfonyl]butan-2-yl]-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-1-[(2S)-1-[(2R)-butan-2-yl]sulfonylbutan-2-yl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-[(3-methyloxetan-3-yl)methylsulfonyl]ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(cyclopropylmethylsulfonyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-2-cyclohexylsulfonyl-1-cyclopropylethyl]-3-ethyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-1-[(2S)-1-tert-butylsulfonylbutan-2-yl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-ethyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-ethylsulfonylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-cyclopropylsulfonylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-propan-2-ylsulfonylethyl]-3-ethyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-pentan-3-ylsulfonylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2S,3S)-2-ethylsulfonylpentan-3-yl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R)-1-[(1S)-2-(tert-butylsulfamoyl)-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
2-[(3R,5R,6S)-1-[(2S)-1-tert-butylsulfonylbutan-2-yl]-5-(3-chloro-5-fluorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.1 nM	US-9593129: Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.89	IC50	0.013	nM	CHEMBL5283210
10.72	IC50	0.019	nM	CHEMBL5272028
10.44	Kd	0.036	nM	CHEMBL3125527
10.42	Kd	0.038	nM	NAVTEMADLIN
10.40	IC50	0.04	nM	CHEMBL3653245
10.35	Kd	0.045	nM	NAVTEMADLIN
10.35	Ki	0.045	nM	CHEMBL4463050
10.30	IC50	0.05	nM	CHEMBL3657031
10.23	IC50	0.059	nM	CHEMBL3318761
10.23	IC50	0.059	nM	CHEMBL3318783
10.23	IC50	0.059	nM	CHEMBL3657124
10.21	IC50	0.061	nM	CHEMBL3892862
10.19	IC50	0.065	nM	CHEMBL3901716
10.17	IC50	0.068	nM	CHEMBL3691776
10.17	IC50	0.068	nM	CHEMBL3945756
10.16	IC50	0.069	nM	CHEMBL3911501
10.15	IC50	0.071	nM	CHEMBL3318768
10.15	IC50	0.07	nM	CHEMBL3639520
10.15	IC50	0.07	nM	CHEMBL3653166
10.15	IC50	0.07	nM	CHEMBL3653231
10.15	IC50	0.071	nM	CHEMBL3920430
10.13	IC50	0.074	nM	CHEMBL3318781
10.13	IC50	0.074	nM	CHEMBL4290086
10.12	IC50	0.075	nM	CHEMBL3318771
10.12	IC50	0.075	nM	CHEMBL3916525
10.11	IC50	0.078	nM	CHEMBL4110580
10.10	IC50	0.079	nM	CHEMBL3318756
10.10	IC50	0.08	nM	CHEMBL3657058
10.10	IC50	0.08	nM	CHEMBL3657040
10.10	IC50	0.08	nM	CHEMBL3657038
10.10	IC50	0.08	nM	CHEMBL3656990
10.10	IC50	0.08	nM	CHEMBL3893972
10.10	IC50	0.079	nM	CHEMBL3928320
10.10	IC50	0.08	nM	CHEMBL3653231
10.09	IC50	0.081	nM	CHEMBL3318758
10.09	IC50	0.081	nM	CHEMBL3657083
10.07	IC50	0.086	nM	CHEMBL3318762
10.06	IC50	0.088	nM	CHEMBL3318782
10.06	IC50	0.087	nM	CHEMBL3895404
10.05	IC50	0.09	nM	CHEMBL3657035
10.05	IC50	0.09	nM	CHEMBL3653173
10.05	IC50	0.09	nM	CHEMBL3653271
10.05	IC50	0.09	nM	CHEMBL3657024
10.05	IC50	0.089	nM	CHEMBL3657117
10.04	IC50	0.091	nM	CHEMBL3318764
10.03	IC50	0.094	nM	CHEMBL3937629
10.02	IC50	0.096	nM	CHEMBL3318767
10.02	IC50	0.095	nM	CHEMBL3916664
10.01	IC50	0.098	nM	CHEMBL3318760
10.01	IC50	0.097	nM	CHEMBL3691779

PubChem BioAssay actives

2453 with measured affinity, of 4567 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(3R,5S,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1R)-2-methyl-1-propan-2-ylsulfonylpropyl]-2-oxopiperidin-3-yl]acetic acid	1555419: Inhibition of p53 protein binding to MDM2 in human SJSA1 cells	ki	<0.0001	uM
4-[[(2R,3S,4S,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-5-(2,2-dimethylpropyl)-4-[(piperidin-4-ylmethylamino)methyl]pyrrolidine-2-carbonyl]amino]-3-methoxybenzoic acid	1908077: Displacement of 5-FAM labeled PDI peptide from MDM2 (1 to 118 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as inhibition constant incubated for 1.5 hrs by fluorescence polarization competition assay	ki	<0.0001	uM
(3R,4S,5S,6R)-2-[4-(2,4-difluorophenyl)triazol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1928056: Inhibition of human DM2-p53 protein-protein interaction by fluorescence anisotropy analysis	ic50	<0.0001	uM
(3R,4S,5S,6R)-2-[4-[(1S)-1-(3-fluorophenyl)-1-hydroxyethyl]triazol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1928056: Inhibition of human DM2-p53 protein-protein interaction by fluorescence anisotropy analysis	ic50	<0.0001	uM
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	1075196: Binding affinity to human MDM2 by by Surface Plasmon Resonace (SPR) spectroscopy binding assay	kd	<0.0001	uM
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	1128403: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli after 1 to 2 mins by surface plasmon resonance spectroscopic analysis	kd	<0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(ethylsulfamoyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(propylsulfamoyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(cyclopropylmethylsulfamoyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(cyclopropylsulfamoyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-2-(cyclobutylsulfamoyl)-1-cyclopropylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-2-(cyclopentylsulfamoyl)-1-cyclopropylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(diethylsulfamoyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(phenylsulfamoyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-[(2-fluorophenyl)sulfamoyl]ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-[ethyl(phenyl)sulfamoyl]ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2S)-3,3-dimethyl-1-[(2R)-2-methylpyrrolidin-1-yl]sulfonylbutan-2-yl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2S)-3,3-dimethyl-1-(4-methylpiperazin-1-yl)sulfonylbutan-2-yl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2S)-3,3-dimethyl-1-piperazin-1-ylsulfonylbutan-2-yl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2S)-1-[(1,1-dioxo-1,4-thiazinan-4-yl)sulfonyl]-3,3-dimethylbutan-2-yl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2S)-1-[(3,3-dimethyl-2H-indol-1-yl)sulfonyl]-3,3-dimethylbutan-2-yl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
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	1195685: Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as inhibition of interaction with human p53 preincubated with compound for 20 mins by HTRF assay	ic50	0.0001	uM
4-[[2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetyl]amino]bicyclo[2.2.2]octane-1-carboxylic acid	1195685: Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as inhibition of interaction with human p53 preincubated with compound for 20 mins by HTRF assay	ic50	0.0001	uM
(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	1421138: Inhibition of Cy5-labeled p53 derived TFSDLWKLL peptide binding to C-terminal biotin-labelled human MDM2 (2 to 188 residues) by TR-FRET assay	ic50	0.0001	uM
(4S)-5-[3-chloro-5-[2-(dimethylamino)ethoxy]phenyl]-4-(4-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	1873011: Inhibition of recombinant human MDM2/p53 interaction	ic50	0.0001	uM
4-[[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino]-3-methoxybenzoic acid	1075196: Binding affinity to human MDM2 by by Surface Plasmon Resonace (SPR) spectroscopy binding assay	kd	0.0001	uM
2-[(3R,5R,6S)-1-[(1S)-2-(tert-butylsulfamoyl)-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-methylsulfonylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-morpholin-4-ylsulfonylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-pyrrolidin-1-ylsulfonylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclopropyl-2-(propan-2-ylsulfamoyl)ethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1184469: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay in presence of 15% human serum	ic50	0.0001	uM
2-[(3R,5R,6S)-1-[(1S)-2-(azetidin-1-ylsulfonyl)-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
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	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
3-[[6-chloro-3-[3-[(1S)-1-(2,4-dichlorophenyl)ethyl]-5-phenylimidazol-4-yl]-1H-indole-2-carbonyl]amino]-4-[4-(2-oxo-1,3-oxazinan-3-yl)piperidin-1-yl]benzoic acid	1908066: Inhibition of human MDM2 by TR-FRET assay	ic50	0.0001	uM
(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	1421138: Inhibition of Cy5-labeled p53 derived TFSDLWKLL peptide binding to C-terminal biotin-labelled human MDM2 (2 to 188 residues) by TR-FRET assay	ic50	0.0001	uM
2-[2-[[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-6-(4-chloro-3-fluorophenyl)-5-(3-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]methyl]-1,3-thiazol-5-yl]acetic acid	1129363: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay	ic50	0.0001	uM
6-[[(2S,5R,6R)-4-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-6-(3-chlorophenyl)-5-(4-chlorophenyl)-2-methyl-3-oxomorpholin-2-yl]methyl]pyridine-3-carboxylic acid	1129363: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay	ic50	0.0001	uM
6-[[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]methyl]pyridine-3-carboxylic acid	1129363: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay	ic50	0.0001	uM
6-[[(2R,5R,6R)-4-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-6-(3-chlorophenyl)-5-(4-chlorophenyl)-2-methyl-3-oxomorpholin-2-yl]methyl]pyridine-3-carboxylic acid	1129363: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay	ic50	0.0001	uM
2-[(3R,5R,6S)-1-[(2S)-1-tert-butylsulfonyl-4,4,4-trifluorobutan-2-yl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
2-[(3R,5R,6S)-1-[(2S)-1-tert-butylsulfonylpropan-2-yl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(1S)-1-cyclobutyl-2-propan-2-ylsulfonylethyl]-3-methyl-2-oxopiperidin-3-yl]acetic acid	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclobutylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	1075194: Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay	ic50	0.0001	uM
2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-6-(4-chloro-3-fluorophenyl)-5-(3-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	1195685: Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as inhibition of interaction with human p53 preincubated with compound for 20 mins by HTRF assay	ic50	0.0001	uM
4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-(5-fluoro-2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	1421138: Inhibition of Cy5-labeled p53 derived TFSDLWKLL peptide binding to C-terminal biotin-labelled human MDM2 (2 to 188 residues) by TR-FRET assay	ic50	0.0001	uM
(4S)-4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	1421138: Inhibition of Cy5-labeled p53 derived TFSDLWKLL peptide binding to C-terminal biotin-labelled human MDM2 (2 to 188 residues) by TR-FRET assay	ic50	0.0001	uM
2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetamide	1129363: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay	ic50	0.0001	uM
4-[[2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetyl]amino]-2-methoxybenzoic acid	1195685: Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as inhibition of interaction with human p53 preincubated with compound for 20 mins by HTRF assay	ic50	0.0001	uM
2-[[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]methyl]pyridine-4-carboxylic acid	1129363: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay	ic50	0.0001	uM
(3R,5R,6S)-1-[(2S)-1-tert-butylsulfonylbutan-2-yl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-3-(2H-tetrazol-5-ylmethyl)piperidin-2-one	1129363: Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay	ic50	0.0001	uM

CTD chemical–gene interactions

267 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases reaction, affects cotreatment, decreases expression, decreases reaction, increases phosphorylation (+4 more)	21
Doxorubicin	affects binding, increases activity, increases expression, increases phosphorylation, decreases response to substance (+4 more)	12
sodium arsenite	increases expression, increases reaction, affects expression, affects cotreatment, decreases expression (+2 more)	11
nutlin 3	affects cotreatment, increases secretion, decreases reaction, affects reaction, increases expression (+5 more)	11
Cisplatin	affects binding, increases reaction, increases activity, increases cleavage, affects reaction (+3 more)	11
Fluorouracil	increases expression, increases reaction, affects reaction, increases phosphorylation	10
Resveratrol	increases reaction, affects binding, decreases reaction, affects cotreatment, increases expression (+2 more)	9
Etoposide	affects reaction, increases phosphorylation, decreases expression, increases expression, decreases response to substance (+2 more)	9
Aflatoxin B1	affects expression, decreases methylation, increases expression	7
bisphenol A	affects expression, increases expression, increases phosphorylation, decreases reaction, affects cotreatment	5
Oxygen	decreases reaction, increases expression, increases reaction, affects cotreatment	5
Quercetin	decreases expression, decreases phosphorylation, increases expression	5
Tobacco Smoke Pollution	decreases expression, increases expression	5
arsenite	increases expression, decreases reaction, decreases stability, increases activity, increases degradation (+3 more)	4
Arsenic Trioxide	decreases expression, increases expression	4
Arsenic	affects response to substance, decreases expression, increases abundance, affects reaction, affects methylation (+1 more)	4
Methotrexate	increases activity, increases expression, increases reaction, affects reaction	4
Tetrachlorodibenzodioxin	increases expression, increases reaction, decreases expression, decreases response to substance, increases phosphorylation (+1 more)	4
Particulate Matter	increases abundance, increases expression, affects expression, decreases expression	4
Curcumin	increases expression, decreases reaction, increases phosphorylation, decreases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Hydrogen Peroxide	decreases expression, decreases reaction, increases expression, affects binding, increases reaction	3
Valproic Acid	affects expression, decreases expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	3
Cyclosporine	increases expression	3
Cadmium Chloride	increases phosphorylation, affects reaction, decreases expression, decreases phosphorylation, increases reaction (+1 more)	3
Sirolimus	decreases reaction, increases phosphorylation, affects binding, increases reaction, decreases expression	3
thymoquinone	decreases expression	2
2,4,5,2’,5’-pentachlorobiphenyl	decreases reaction, increases phosphorylation, decreases phosphorylation	2
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases phosphorylation, decreases reaction	2

ChEMBL screening assays

1007 unique, capped per target: 979 binding, 28 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1040569	Binding	Inhibition of MDM2-p53 interaction in human SJSA1 cells assessed as p53 activation by Western blot	Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. — J Med Chem
CHEMBL907753	Functional	Induction of p53 dependent transcription in SJSA cell line by reporter gene assay	Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. — J Med Chem

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D272	MDM2-RNB	Transformed cell line	Sex unspecified
CVCL_D8QI	Ubigene HCT 116 MDM2 KO	Cancer cell line	Male
CVCL_D9K3	Ubigene HEK293 MDM2 KO	Transformed cell line	Female
CVCL_E0HT	Ubigene HeLa MDM2 KO	Cancer cell line	Female
CVCL_SX67	HAP1 MDM2 (-) 1	Cancer cell line	Male
CVCL_SX68	HAP1 MDM2 (-) 2	Cancer cell line	Male
CVCL_VS52	QIMR-SB2b	Cancer cell line	Male

Clinical trials (associated diseases)

21 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01464086	PHASE3	COMPLETED	LIFSCREEN : Evaluation of Whole Body MRI for Early Detection of Cancers in Subjects With P53 Mutation (Li-Fraumeni Syndrome)
NCT06088030	PHASE2	RECRUITING	Arsenic Trioxide Combined With Chemotherapy for the Treatment of p53-mutated Pediatric Cancer
NCT01981525	PHASE1	COMPLETED	A Pilot Study of Metformin in Patients With a Diagnosis of Li-Fraumeni Syndrome
NCT00406445	Not specified	COMPLETED	Role of p53 Gene in Metabolism Regulation in Patients With Li-Fraumeni Syndrome
NCT01143454	Not specified	RECRUITING	Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System
NCT01443468	Not specified	RECRUITING	Clinical and Genetic Studies of Li-Fraumeni Syndrome
NCT01737255	Not specified	COMPLETED	Magnetic Resonance Imaging Screening in Li Fraumeni Syndrome
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02950987	Not specified	ACTIVE_NOT_RECRUITING	Screening With Whole Body MRI For Detection Of Primary Tumors In Children And Adults With Li-Fraumeni Syndrome (LFS) And Other Cancer Predisposition Syndromes
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03176836	Not specified	ENROLLING_BY_INVITATION	Li-Fraumeni Syndrome Imaging Study
NCT04367246	Not specified	RECRUITING	Li-Fraumeni Syndrome/TP53 Biobank
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04966923	Not specified	COMPLETED	Phenotype and Prognosis of Patients With Breast Cancer and Pathogenic Variants of TP53
NCT04982744	Not specified	RECRUITING	Registry of Li Fraumeni and Li Fraumeni Like Syndromes
NCT05126810	Not specified	RECRUITING	Willingness to Participate in a Trial Comparing Standard Genetic Counseling Versus Personalized Genetic Counseling
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
NCT06712095	Not specified	RECRUITING	Video Capsule Examination in Patients With Lynch Syndrome
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07032922	Not specified	COMPLETED	Exploring How to Adapt an Evidence-Based Mindful Self-Compassion Program for Young Adults With Li-Fraumeni Syndrome