MDM4

Summary

MDM4 (MDM4 regulator of p53, HGNC:6974) is a protein-coding gene on chromosome 1q32.1, encoding Protein Mdm4 (O15151). Contributes to p53/TP53 regulation. It is a selective cancer dependency (DepMap: 11.8% of cell lines).

This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter’s degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.

Source: NCBI Gene 4194 — RefSeq curated summary.

At a glance

• Gene–disease (curated): bone marrow failure syndrome 6 (Moderate, ClinGen) — +1 more curated relationship
• GWAS associations: 25
• Clinical variants (ClinVar): 74 total — 1 pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 11.8% of screened cell lines
• MANE Select transcript: NM_002393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6974
Approved symbol	MDM4
Name	MDM4 regulator of p53
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	MDMX, HDMX
Ensembl gene	ENSG00000198625
Ensembl biotype	protein_coding
OMIM	602704
Entrez	4194

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000367179, ENST00000367180, ENST00000367182, ENST00000367183, ENST00000454264, ENST00000462012, ENST00000463049, ENST00000470797, ENST00000470908, ENST00000471783, ENST00000612738, ENST00000614459, ENST00000616250, ENST00000880814, ENST00000880815, ENST00000880816, ENST00000880817, ENST00000922675, ENST00000922676, ENST00000922677, ENST00000922678, ENST00000922679, ENST00000959566, ENST00000959567, ENST00000959568

RefSeq mRNA: 7 — MANE Select: NM_002393 NM_001204171, NM_001204172, NM_001278516, NM_001278517, NM_001278518, NM_001278519, NM_002393

CCDS: CCDS1447, CCDS55674, CCDS55675, CCDS60396, CCDS73007, CCDS73008, CCDS73009

Canonical transcript exons

ENST00000367182 — 11 exons

Exon	Start	End
ENSE00001039927	204537430	204537497
ENSE00001123001	204549113	204558120
ENSE00001841654	204516406	204516509
ENSE00003495179	204532191	204532246
ENSE00003526016	204530684	204530817
ENSE00003552617	204525484	204525596
ENSE00003622295	204544535	204544684
ENSE00003656110	204526360	204526434
ENSE00003662322	204546797	204546877
ENSE00003686502	204542784	204542944
ENSE00003687904	204538209	204538308

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 98.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.2008 / max 597.0157, expressed in 1806 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7971	30.1489	1804
7985	3.1563	1107
7972	0.7779	456
7970	0.6210	384
7973	0.1057	59
201896	0.1016	33
7975	0.0875	14
7974	0.0794	37
7976	0.0366	10
7980	0.0240	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	98.24	gold quality
oocyte	CL:0000023	97.86	gold quality
colonic epithelium	UBERON:0000397	97.83	gold quality
trabecular bone tissue	UBERON:0002483	97.76	gold quality
upper leg skin	UBERON:0004262	97.43	gold quality
pylorus	UBERON:0001166	96.82	gold quality
calcaneal tendon	UBERON:0003701	96.77	gold quality
sural nerve	UBERON:0015488	96.71	gold quality
cardia of stomach	UBERON:0001162	96.67	gold quality
pericardium	UBERON:0002407	96.58	gold quality
superior surface of tongue	UBERON:0007371	96.52	gold quality
seminal vesicle	UBERON:0000998	96.21	gold quality
corpus callosum	UBERON:0002336	96.19	gold quality
trigeminal ganglion	UBERON:0001675	96.14	gold quality
superficial temporal artery	UBERON:0001614	96.10	gold quality
epithelium of nasopharynx	UBERON:0001951	96.08	gold quality
skin of hip	UBERON:0001554	95.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.85	gold quality
inferior vagus X ganglion	UBERON:0005363	95.84	gold quality
mammalian vulva	UBERON:0000997	95.72	gold quality
adult organism	UBERON:0007023	95.71	gold quality
corpus epididymis	UBERON:0004359	95.68	gold quality
renal medulla	UBERON:0000362	95.60	gold quality
tendon	UBERON:0000043	95.54	gold quality
buccal mucosa cell	CL:0002336	95.41	gold quality
penis	UBERON:0000989	95.39	gold quality
caput epididymis	UBERON:0004358	95.20	gold quality
saphenous vein	UBERON:0007318	95.10	gold quality
secondary oocyte	CL:0000655	94.94	gold quality
cauda epididymis	UBERON:0004360	94.93	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	744.46
E-MTAB-9067	yes	13.20
E-MTAB-6678	yes	4.92
E-CURD-122	yes	4.36
E-CURD-97	no	670.07
E-GEOD-124858	no	473.03
E-MTAB-9801	no	4.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TP53	Unknown

Upstream regulators (CollecTRI, top): ELK1, ETS1, TP53, TP73

miRNA regulators (miRDB)

339 targeting MDM4, 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-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AW	99.99	72.57	3559

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• stability is regulated by p53-induced caspase cleavage, which plays an important functional role. proteolytic modifications may regulate its intracellular levels (PMID:11840332)
• MDMX, when exceedingly overexpressed, inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding (PMID:11953423)
• MDMX dramatically inhibits the acetylation of p53 induced by both endogenous and ectopically expressed p300/CBP. (PMID:12162806)
• MDMX is transported to the cell nucleus upon DNA damage with or without p53 (PMID:12370303)
• MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination (PMID:12393902)
• Smad-induced transactivation by MdmX occurs by altering Smad interaction with its coactivator p300 (PMID:12483531)
• mouse double minute 4 homolog gene amplification is associated with malignant gliomas on 1q32 (PMID:12640683)
• MDMX is ubiquinated and degraded by MDM2 (PMID:12860999)
• DNA damage-induced MDMX degradation is mediated by MDM2 (PMID:12963717)
• findings reveal a novel role for MDM4 protein by demonstrating that in non-tumor cells under stress conditions it may act as a positive regulator of p53 protein activity (PMID:14660608)
• MdmX represses E2F1 transactivation (PMID:14739777)
• hMdmx is overexpressed in a significant percentage of various human tumors and amplified in 5% of primary breast tumors, all of which retained wild-type p53. iRNA-mediated reduction of hMdmx inhibited cell growth potential in a p53-dependent manner (PMID:15199139)
• Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53. (PMID:15782125)
• sites important for Hdm2-mediated ubiquitination of Hdmx after double-strand break induction (PMID:15788536)
• MdmX can affect post-translational modification and stability of Mdm2 and p53 activity through interaction with ARF (PMID:15876864)
• HDMX gene was amplified in 17% of soft tissue sarcoma patienets and gene amplification was associated with poor prognosis. (PMID:15906355)
• sumoylation-deficient MDMX mutant undergoes normal ubiquitination and degradation by MDM2, normal nuclear translocation and degradation after DNA damage, and inhibits p53 with wild type efficiency (PMID:15907800)
• identification of functionally different alleles of genes and suggestion that the different alleles at this SNP locus in the MRP1 gene may account, in part, for inter-individual variations and population differences in drug response (PMID:15944197)
• deletion of Mdm4 enhances the ability of Mdm2 to promote cell growth and tumor formation, indicating that Mdm4 has antioncogenic properties when Mdm2 is overexpressed (PMID:16027727)
• ATM directly activates p53 while activating a safe-lock mechanism to inactivate the negative regulators of p53, Mdm2, and Mdmx [review] (PMID:16082221)
• ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. (PMID:16163388)
• MdmX may have different roles in the regulation of Mdm2 activity for ubiquitination of pRB and p53 (PMID:16510145)
• Mdm4 regulates tumor suppressor p53 activity, while Mdm2 mainly controls p53 stability (PMID:16616333)
• These results demonstrate a sophisticated control by ATM of a target protein, Hdmx, which itself is one of several ATM targets in the ATM-p53 axis of the DNA damage response. (PMID:16943424)
• MDM4 is alternatively spliced following UV irradiation. Alternate forms of MDM4 place selective pressure on the cells to acquire additional alterations in the p53 pathway. (PMID:17018606)
• amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells (PMID:17080083)
• MDMX is an important regulator of p53 response to ribosomal stress and RNA-targeting chemotherapy agents. (PMID:17110929)
• functions of the extreme C-terminus of MDM2 can be provided by MDMX (PMID:17159902)
• the MDM2 and MDMX complex has a role in abundance and activity of p53 (PMID:17616658)
• Expression of both MDM2 and MDM4 in tumors without p53 mutations strongly suggests that MDM2 and MDM4 inhibit the activity of this tumor suppressor in head and neck squamous carcinomas. (PMID:17651783)
• These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G(1) and early S phases. (PMID:18086887)
• MDMX expression is regulated by mitogenic signaling pathways. This mechanism may protect normal proliferating cells from p53 but also hamper p53 response during tumor development. (PMID:18172009)
• There is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients. (PMID:18279506)
• Levels of MDM2, MDM4, and its variants, MDM4-S (originally HDMX-S) and MDM4-211 (originally HDMX211), in a group of 57 papillary thyroid carcinomas, were estimated. (PMID:18335186)
• stabilization of MDMX by Akt may be an alternative mechanism by which Akt up-regulates MDM2 protein levels and exerts its oncogenic effects on p53 in tumor cells (PMID:18356162)
• data indicate that gain/amplification and overexpression of MDM4 is a novel molecular mechanism by which a subset of urothelial cell carcinoma escapes p53-dependent growth control, thus providing new avenues for therapeutic intervention. (PMID:18451213)
• Overexpression of MDM2 and MDM4 is not a necessary step in retinoblastoma development. (PMID:18644346)
• Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain. (PMID:18677113)
• MDM4 gain is associated with the early transition from normal retina to retinoma. (PMID:18785023)
• the presence of conserved and non-conserved interactions along the conformational transition pathway that may be exploited in the design of selective and dual modulators of MDMX activity (PMID:18826207)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mdm4	ENSDARG00000057513
mus_musculus	Mdm4	ENSMUSG00000054387
rattus_norvegicus	Mdm4	ENSRNOG00000009696

Paralogs (1): MDM2 (ENSG00000135679)

Protein

Protein identifiers

Protein Mdm4 — O15151 (reviewed: O15151)

Alternative names: Double minute 4 protein, Mdm2-like p53-binding protein, Protein Mdmx, p53-binding protein Mdm4

All UniProt accessions (8): A0A087WTR9, A0A087WUE3, A0A087WZ58, O15151, Q5T0Y2, Q5T0Y4, Q68DC0, Q6MZR7

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to p53/TP53 regulation. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding their transcriptional activation domains. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.

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 MDM2; enhances the ubiquitin ligase activity of MDM2 on TP53. Interacts with TP53. Interacts with TP73 and USP2. Found in a trimeric complex with USP2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53. Interacts with RAD54B; RAD54B enhances the ubiquitin ligase activity of MDM2 on TP53 by promoting MDM2-MDM4 heterodimerization.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in all tissues tested with high levels in thymus.

Post-translational modifications. Phosphorylated. Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation. Phosphorylation at Ser-342 also induces ubiquitination and degradation but to a lower extent. Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein.

Disease relevance. Bone marrow failure syndrome 6 (BMFS6) [MIM:618849] A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS6 is an autosomal dominant form characterized by intermittent neutropenia, lymphopenia, or anemia associated with hypocellular bone marrow, and increased susceptibility to cancer. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Region I is sufficient for binding TP53 and inhibiting its G1 arrest and apoptosis functions. It also binds TP73. Region II contains most of a central acidic region and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc mediates the heterooligomerization with MDM2.

Induction. Down-regulated by cisplatin (at protein level).

Miscellaneous. Cancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation.

Similarity. Belongs to the MDM2/MDM4 family.

Isoforms (5)

UniProt ID	Names	Canonical?
O15151-1	1	yes
O15151-2	2, MDMX-S
O15151-3	3, MDMX
O15151-4	HDMX211
O15151-5	5

RefSeq proteins (7): NP_001191100, NP_001191101, NP_001265445, NP_001265446, NP_001265447, NP_001265448, NP_002384* (*=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
IPR015458	MDM4	Family
IPR016495	p53_neg-reg_MDM_2/4	Family
IPR036443	Znf_RanBP2_sf	Homologous_superfamily
IPR036885	SWIB_MDM2_dom_sf	Homologous_superfamily
IPR051652	MDM2_MDM4_MUL1	Family

Pfam: PF00641, PF13920

UniProt features (42 total): strand 11, helix 7, splice variant 4, region of interest 4, sequence variant 3, turn 3, modified residue 2, zinc finger region 2, chain 1, domain 1, mutagenesis site 1, sequence conflict 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

39 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6Q9Y	X-RAY DIFFRACTION	1.2
3FEA	X-RAY DIFFRACTION	1.33
3FE7	X-RAY DIFFRACTION	1.35
3FDO	X-RAY DIFFRACTION	1.4
3LBJ	X-RAY DIFFRACTION	1.5
4RXZ	X-RAY DIFFRACTION	1.55
6Q9W	X-RAY DIFFRACTION	1.55
3EQY	X-RAY DIFFRACTION	1.63
7C3Y	X-RAY DIFFRACTION	1.63
7C44	X-RAY DIFFRACTION	1.65
8HDG	X-RAY DIFFRACTION	1.73
3JZP	X-RAY DIFFRACTION	1.74
3JZO	X-RAY DIFFRACTION	1.8
3JZQ	X-RAY DIFFRACTION	1.8
3MQR	X-RAY DIFFRACTION	1.8
3U15	X-RAY DIFFRACTION	1.8
7C3Q	X-RAY DIFFRACTION	1.8
3DAB	X-RAY DIFFRACTION	1.9
8IA5	X-RAY DIFFRACTION	1.93
2VYR	X-RAY DIFFRACTION	2
6Q9Q	X-RAY DIFFRACTION	2.1
6YR7	X-RAY DIFFRACTION	2.1
7EL4	X-RAY DIFFRACTION	2.11
5MNJ	X-RAY DIFFRACTION	2.16
2VJE	X-RAY DIFFRACTION	2.2
6YR5	X-RAY DIFFRACTION	2.25
2VJF	X-RAY DIFFRACTION	2.3
6Q9S	X-RAY DIFFRACTION	2.4
6Q9U	X-RAY DIFFRACTION	2.4
5VK1	X-RAY DIFFRACTION	2.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15151-F1	60.78	0.27

Antibody-complex structures (SAbDab): 1 — 2VYR

Functional residue map

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

Post-translational modifications (2): 342, 367

Mutagenesis-validated functional residues (1):

Position	Phenotype
437	fails to interact with mdm2.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559585	Oncogene Induced Senescence
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-1640170	Cell Cycle
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-392499	Metabolism of proteins
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-6806003	Regulation of TP53 Expression and Degradation
R-HSA-69563	p53-Dependent G1 DNA Damage Response
R-HSA-69580	p53-Dependent G1/S DNA damage checkpoint
R-HSA-69615	G1/S DNA Damage Checkpoints
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 367 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, MAZ_Q6, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ENDOCARDIAL_CUSHION_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, RODRIGUES_NTN1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, CATRRAGC_UNKNOWN, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CARDIAC_ATRIUM_DEVELOPMENT, GOBP_ATRIAL_SEPTUM_DEVELOPMENT

GO Biological Process (20): negative regulation of transcription by RNA polymerase II (GO:0000122), heart valve development (GO:0003170), atrioventricular valve morphogenesis (GO:0003181), endocardial cushion morphogenesis (GO:0003203), ventricular septum development (GO:0003281), atrial septum development (GO:0003283), negative regulation of cell population proliferation (GO:0008285), protein ubiquitination (GO:0016567), DNA damage response, signal transduction by p53 class mediator (GO:0030330), negative regulation of protein catabolic process (GO:0042177), negative regulation of apoptotic process (GO:0043066), negative regulation of DNA-templated transcription (GO:0045892), protein stabilization (GO:0050821), regulation of cell cycle (GO:0051726), protein-containing complex assembly (GO:0065003), cellular response to hypoxia (GO:0071456), negative regulation of signal transduction by p53 class mediator (GO:1901797), regulation of cell population proliferation (GO:0042127), protein-containing complex organization (GO:0043933), regulation of biological quality (GO:0065008)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription repressor complex (GO:0017053)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Regulation of TP53 Activity	3
Cellular Senescence	2
Deubiquitination	1
Regulation of TP53 Expression and Degradation	1
p53-Dependent G1 DNA Damage Response	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Post-translational protein modification	1
Metabolism of proteins	1
p53-Dependent G1/S DNA damage checkpoint	1
G1/S DNA Damage Checkpoints	1
Cell Cycle Checkpoints	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cardiac septum development	2
cell population proliferation	2
signal transduction by p53 class mediator	2
regulation of cellular process	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
heart development	1
anatomical structure development	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
regulation of cell population proliferation	1
negative regulation of cellular process	1
protein modification by small protein conjugation	1
signal transduction in response to DNA damage	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of protein stability	1
cell cycle	1
cellular component assembly	1
protein-containing complex organization	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
regulation of signal transduction by p53 class mediator	1
negative regulation of intracellular signal transduction	1
cellular component organization	1

Protein interactions and networks

STRING

2824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MDM4	TP53	P04637	998
MDM4	MDM2	Q00987	986
MDM4	TCHP	Q9BT92	863
MDM4	ATM	Q13315	802
MDM4	CDKN2A	P42771	795
MDM4	BRCA1	P38398	770
MDM4	USP7	Q93009	768
MDM4	CSNK1A1	P48729	756
MDM4	PPM1D	O15297	728
MDM4	E2F1	Q01094	663
MDM4	CCND1	P24385	652
MDM4	RPL11	P25121	648
MDM4	IDH1	O75874	645
MDM4	HIPK2	Q9H2X6	617
MDM4	TP73	O15350	613

IntAct

191 interactions, top by confidence:

A	B	Type	Score
TP53	MDM4	psi-mi:“MI:0915”(physical association)	0.970
TP53	MDM4	psi-mi:“MI:0914”(association)	0.970
TP53	MDM4	psi-mi:“MI:0407”(direct interaction)	0.970
MDM4	TP53	psi-mi:“MI:0407”(direct interaction)	0.970
MDM4	TP53	psi-mi:“MI:0914”(association)	0.970
MDM4	TP53	psi-mi:“MI:0220”(ubiquitination reaction)	0.970
MDM4	TP53	psi-mi:“MI:2364”(proximity)	0.970
TP53	MDM4	psi-mi:“MI:0403”(colocalization)	0.970
MDM4	TP53	psi-mi:“MI:0915”(physical association)	0.970
MDM2	MDM4	psi-mi:“MI:0915”(physical association)	0.940
MDM4	MDM2	psi-mi:“MI:0915”(physical association)	0.940

BioGRID (416): CD160 (Two-hybrid), CAPN7 (Two-hybrid), RNF115 (Two-hybrid), MDM4 (Reconstituted Complex), MDM4 (Affinity Capture-Western), RAD54B (Affinity Capture-Western), SMARCA2 (Reconstituted Complex), RAD54B (Reconstituted Complex), MDM2 (Reconstituted Complex), MDM4 (Reconstituted Complex), MDM2 (Affinity Capture-Western), MDM4 (Affinity Capture-Western), MDM4 (Reconstituted Complex), MDM4 (Affinity Capture-MS), MDM4 (Affinity Capture-MS)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A7YWH3, B1WBU4, O15151, O35618, O43298, O88850, P24278, P97303, Q01954, Q0V8G8, Q15916, Q17RG1, Q562E2, Q5RC05, Q5RDQ6, Q5SXH7, Q5TC79, Q5VYS8, Q5W0Q7, Q5XIN1, Q6ZPY5, Q6ZSB9, Q6ZU67, Q7ZUW7, Q7ZYI3, Q8BLK9, Q8BSV3, Q8IW35, Q8K088, Q8N680, Q8N7W2, Q8TCN5, Q8VHI4, Q8WW38, Q90W33, Q96BR9, Q96S38, Q99ME3

Diamond homologs: B3H754, F4ISV9, O15151, O35618, P23804, P56273, P56950, P56951, Q00987, Q0WS06, Q2HJ21, Q5XIN1, Q60524, Q6DBH0, Q7YRZ8, Q7ZUW7, Q7ZYI3, O42354, Q84ME1, Q8LA32, Q9LYW5

SIGNOR signaling

24 interactions.

A	Effect	B	Mechanism
CDK1	down-regulates	MDM4	phosphorylation
MDM4	“up-regulates quantity by stabilization”	MDM2
ATM	down-regulates	MDM4	phosphorylation
USP7	up-regulates	MDM4	deubiquitination
CHEK2	down-regulates	MDM4	phosphorylation
MDM2	down-regulates	MDM4	ubiquitination
ATM	“down-regulates quantity by destabilization”	MDM4	phosphorylation
AKT	“up-regulates activity”	MDM4	phosphorylation
CHEK1	“down-regulates quantity by destabilization”	MDM4	phosphorylation
CHEK2	“down-regulates quantity by destabilization”	MDM4	phosphorylation
58131-57-0	down-regulates	MDM4	“chemical inhibition”
CSNK1A1	up-regulates	MDM4	phosphorylation
CHEK1	“down-regulates activity”	MDM4	phosphorylation
AKT1	“up-regulates quantity by stabilization”	MDM4	phosphorylation
Ub:E2	“up-regulates activity”	MDM4	ubiquitination
MDM4	“up-regulates quantity by stabilization”	MDM2	binding
PPM1D	“up-regulates quantity by stabilization”	MDM4	dephosphorylation
PELI1	“up-regulates activity”	MDM4	ubiquitination
58131-57-0	“down-regulates activity”	MDM4	“chemical inhibition”
MDM4	“down-regulates quantity by destabilization”	TP53	ubiquitination
MDM4	“down-regulates quantity by destabilization”	MDM4	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
Activation of BAD and translocation to mitochondria	8	148.6×	5e-14
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	131.1×	7e-14
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	131.1×	7e-14
Activation of BH3-only proteins	8	96.9×	1e-12
Intrinsic Pathway for Apoptosis	8	57.1×	8e-11
RHO GTPases activate PKNs	7	54.2×	3e-09
FOXO-mediated transcription	6	49.1×	7e-08
Regulation of TP53 Degradation	5	35.7×	6e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	37.4×	5e-05
regulation of protein localization	6	25.2×	5e-05
negative regulation of cell growth	6	17.6×	2e-04
intracellular protein localization	8	17.1×	1e-05
protein polyubiquitination	6	14.1×	4e-04
cellular response to hypoxia	5	12.4×	2e-03
regulation of cell cycle	7	10.7×	4e-04
protein ubiquitination	8	6.8×	1e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	46
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4820129	NC_000001.10:g.204445085_205890679dup	Pathogenic

SpliceAI

1946 predictions. Top by Δscore:

Variant	Effect	Δscore
1:204516505:G:GG	donor_gain	1.0000
1:204525482:A:AG	acceptor_gain	1.0000
1:204525483:G:GG	acceptor_gain	1.0000
1:204525483:GT:G	acceptor_gain	1.0000
1:204525483:GTT:G	acceptor_gain	1.0000
1:204525483:GTTT:G	acceptor_gain	1.0000
1:204525483:GTTTT:G	acceptor_gain	1.0000
1:204525598:T:G	donor_loss	1.0000
1:204526354:TATCA:T	acceptor_loss	1.0000
1:204526356:TCAGG:T	acceptor_loss	1.0000
1:204526357:CAGG:C	acceptor_loss	1.0000
1:204526358:AGGTA:A	acceptor_loss	1.0000
1:204526359:G:A	acceptor_loss	1.0000
1:204526432:GAG:G	donor_gain	1.0000
1:204538205:TCA:T	acceptor_loss	1.0000
1:204538206:CA:C	acceptor_loss	1.0000
1:204538207:A:AC	acceptor_loss	1.0000
1:204538207:A:AG	acceptor_gain	1.0000
1:204538208:G:GG	acceptor_gain	1.0000
1:204538208:GC:G	acceptor_gain	1.0000
1:204538208:GCA:G	acceptor_gain	1.0000
1:204538208:GCAA:G	acceptor_gain	1.0000
1:204538208:GCAAA:G	acceptor_gain	1.0000
1:204538307:AGG:A	donor_loss	1.0000
1:204538309:G:GA	donor_loss	1.0000
1:204538310:T:A	donor_loss	1.0000
1:204542779:TATA:T	acceptor_loss	1.0000
1:204542781:T:G	acceptor_gain	1.0000
1:204542782:A:AG	acceptor_gain	1.0000
1:204542782:A:T	acceptor_loss	1.0000

AlphaMissense

3243 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:204549125:T:C	C306R	0.998
1:204549167:T:C	C320R	0.998
1:204549125:T:A	C306S	0.997
1:204549126:G:C	C306S	0.997
1:204549169:T:G	C320W	0.997
1:204549176:T:A	C323S	0.997
1:204549176:T:C	C323R	0.997
1:204549177:G:C	C323S	0.997
1:204526391:T:C	L37S	0.996
1:204530798:T:C	F90L	0.996
1:204530800:C:A	F90L	0.996
1:204530800:C:G	F90L	0.996
1:204549119:T:A	W304R	0.996
1:204549119:T:C	W304R	0.996
1:204549168:G:A	C320Y	0.996
1:204549587:T:C	C460R	0.996
1:204549600:C:A	A464D	0.996
1:204549629:T:C	C474R	0.996
1:204530799:T:C	F90S	0.995
1:204549121:G:C	W304C	0.995
1:204549121:G:T	W304C	0.995
1:204549134:T:A	C309S	0.995
1:204549135:G:C	C309S	0.995
1:204549178:T:G	C323W	0.995
1:204549518:T:C	C437R	0.995
1:204530772:T:C	L81S	0.994
1:204549127:T:G	C306W	0.994
1:204549134:T:C	C309R	0.994
1:204549167:T:A	C320S	0.994
1:204549168:G:C	C320S	0.994

dbSNP variants (sampled 300 via entrez): RS1000021179 (1:204557354 T>A), RS1000067274 (1:204557102 A>C), RS1000086224 (1:204521149 T>C), RS1000095008 (1:204517255 G>GA), RS1000164212 (1:204539757 A>G), RS1000215959 (1:204539913 G>C), RS1000268341 (1:204527906 C>G,T), RS1000329478 (1:204527543 T>C), RS1000369930 (1:204527877 C>T), RS1000400717 (1:204555860 CA>C,CAA), RS1000461029 (1:204552166 A>G), RS1000493322 (1:204533472 T>G), RS1000524626 (1:204552574 G>A), RS1000526386 (1:204521432 C>G,T), RS1000535689 (1:204521531 C>T)

Disease associations

OMIM: gene MIM:602704 | disease phenotypes: MIM:618849, MIM:101600

GenCC curated gene-disease

Disease	Classification	Inheritance
bone marrow failure syndrome	Moderate	Autosomal dominant
bone marrow failure syndrome 6	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
bone marrow failure syndrome 6	Moderate	AD

Mondo (3): bone marrow failure syndrome 6 (MONDO:0030015), Pfeiffer syndrome (MONDO:0007043), bone marrow failure syndrome (MONDO:0000159)

Orphanet (1): Pfeiffer syndrome (Orphanet:710)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0003326	Myalgia
HP:0005518	Increased mean corpuscular volume
HP:0005528	Bone marrow hypocellularity
HP:0011108	Recurrent sinusitis
HP:0011904	Persistence of hemoglobin F
HP:0012432	Chronic fatigue
HP:0030413	Squamous cell carcinoma of the tongue
HP:0031413	Short telomere length

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000477_53	Cognitive performance	5.000000e-06
GCST001916_3	Breast Cancer in BRCA1 mutation carriers	1.000000e-07
GCST001930_14	Breast cancer	2.000000e-12
GCST001942_20	Prostate cancer	2.000000e-11
GCST002305_1	Breast cancer (estrogen-receptor negative, progesterone-receptor negative, and human epidermal growth factor-receptor negative)	4.000000e-06
GCST003842_2	Breast cancer (estrogen-receptor negative)	6.000000e-15
GCST003845_3	Breast cancer	8.000000e-18
GCST004347_1	Glioma	3.000000e-07
GCST004348_13	Non-glioblastoma glioma	3.000000e-09
GCST005076_8	Breast cancer (estrogen-receptor negative)	3.000000e-23
GCST006166_16	Diastolic blood pressure x alcohol consumption interaction (2df test)	4.000000e-09
GCST006187_4	Diastolic blood pressure (cigarette smoking interaction)	2.000000e-09
GCST006258_43	Diastolic blood pressure	5.000000e-09
GCST006259_27	Systolic blood pressure	1.000000e-06
GCST006922_4	Regular attendance at a religious group	3.000000e-08
GCST007268_79	Diastolic blood pressure	6.000000e-09
GCST010118_8	Type 2 diabetes	3.000000e-08
GCST010135_42	Oily fish consumption	2.000000e-08
GCST010140_32	Pork consumption	2.000000e-08
GCST010142_21	Fish- and plant-related diet	9.000000e-10
GCST010322_2	Levodopa wearing off effect (time symptoms uncontrolled) in Parkinson’s disease (response to zonisamide)	4.000000e-08
GCST90000025_842	Appendicular lean mass	4.000000e-16
GCST90002381_13	Eosinophil count	2.000000e-11
GCST90002382_23	Eosinophil percentage of white cells	6.000000e-12
GCST90014033_4	Haemorrhoidal disease	3.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0009592	social interaction measurement
EFO:0008111	diet measurement
EFO:0010747	response to levodopa
EFO:0010749	motor function measurement
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1255126 (SINGLE PROTEIN), CHEMBL2221344 (PROTEIN-PROTEIN INTERACTION), CHEMBL3883306 (PROTEIN-PROTEIN INTERACTION), CHEMBL4106123 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 26,762 (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
CHEMBL231884	DIOSMIN	4	4,880
CHEMBL5314346	VERTEPORFIN	4
CHEMBL3653256	SIREMADLIN	2	1,320
CHEMBL359965	ALLICIN	2	14,806
CHEMBL2381408	SAR-405838	1	547
CHEMBL3601398	CGM-097	1	921
CHEMBL376408	ABT 737	1	4,288

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1563828	Efficacy	3	docetaxel;epirubicin	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1563828	MDM4	3	2.50	1	docetaxel;epirubicin

Binding affinities (BindingDB)

302 measured of 306 human assays (306 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
(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
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
(4S)-5-[5-chloro-2-[2-(dimethylamino)ethoxy]phenyl]-4-(4-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.101 nM	US-8969341: Pyrazolopyrrolidine compounds
3-[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	0.116 nM	US-9365576: Pyrrolopyrrolidinone compounds
3-[(6S)-5-(3-chloro-2-fluorophenyl)-6-(4-chloro-2-methylphenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-N-methylbenzamide	IC50	0.119 nM	US-9365576: Pyrrolopyrrolidinone compounds
3-[5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-N-(2-hydroxyethoxy)-4-methoxybenzamide	IC50	0.125 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-methoxybenzonitrile	IC50	0.14 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
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	0.14 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-c]pyrazol-6-one	IC50	0.146 nM	US-8969341: Pyrazolopyrrolidine 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]-N-(2-hydroxyethyl)-4-methoxybenzamide	IC50	0.15 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
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-propan-2-ylbenzamide	IC50	0.15 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-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.161 nM	US-8969341: Pyrazolopyrrolidine compounds
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	IC50	0.17 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-(2-fluoro-6-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.17 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
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	0.17 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
5-(3-chloro-2-fluorophenyl)-4-(4-chlorophenyl)-2-[5-(hydroxymethyl)-2-methoxyphenyl]-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.17 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
5-(3-chloro-2-fluorophenyl)-4-(4-chlorophenyl)-2-[2-methoxy-5-(morpholine-4-carbonyl)phenyl]-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.18 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
4-(4-chlorophenyl)-5-[5-chloro-2-(2H-tetrazol-5-ylmethoxy)phenyl]-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.18 nM	US-8969341: Pyrazolopyrrolidine compounds
3-[4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-2-yl]-4-methoxybenzonitrile	IC50	0.187 nM	US-8969341: Pyrazolopyrrolidine compounds
3-[4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-2-yl]-4-methoxy-N,N-dimethylbenzamide	IC50	0.195 nM	US-8969341: Pyrazolopyrrolidine 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-methylbenzamide	IC50	0.2 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-(3-methoxy-4-pyridinyl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.22 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-2-yl]-4-methoxy-N-(2-pyrrolidin-1-ylethyl)benzamide	IC50	0.238 nM	US-8969341: Pyrazolopyrrolidine compounds
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	IC50	0.25 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
3-[5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-4-(4-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-2-yl]-4-methoxy-N-methylbenzamide	IC50	0.259 nM	US-8969341: Pyrazolopyrrolidine compounds
5-[5-chloro-1-(2-methoxyethyl)-6-oxo-3-pyridinyl]-4-(4-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.267 nM	US-8969341: Pyrazolopyrrolidine compounds
5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-4-(4-isocyanophenyl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.27 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
5-(5-chloro-2-methylphenyl)-6-(4-chlorophenyl)-2-(2-methoxyphenyl)-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-4-one	IC50	0.298 nM	US-9365576: Pyrrolopyrrolidinone compounds
5-(5-chloro-1-ethyl-6-oxo-3-pyridinyl)-4-(4-chlorophenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.377 nM	US-8969341: Pyrazolopyrrolidine compounds
5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-4-(4-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.393 nM	US-8969341: Pyrazolopyrrolidine compounds
5-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.41 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
5-(5-chloro-1-ethyl-6-oxo-3-pyridinyl)-4-(4-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.42 nM	US-8969341: Pyrazolopyrrolidine compounds
5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-4-(4-chlorophenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.425 nM	US-8969341: Pyrazolopyrrolidine compounds
methyl 3-[5-(3-chloro-4-fluorophenyl)-4-(4-chlorophenyl)-2-(2-methoxyphenyl)-6-oxo-3-propan-2-ylpyrrolo[3,4-c]pyrazol-4-yl]propanoate	IC50	0.499 nM	US-8969341: Pyrazolopyrrolidine compounds
5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-4-(4-isocyanophenyl)-2-[4-methoxy-2-(methylamino)pyrimidin-5-yl]-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.6 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-3-propan-2-yl-2-[2-(trifluoromethoxy)phenyl]-4H-pyrrolo[3,4-d]imidazol-6-one	IC50	0.65 nM	US-8815926: Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-2-[2-(4-methylpiperazin-1-yl)ethyl]-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.7 nM	US-8969341: Pyrazolopyrrolidine compounds
4-(4-chlorophenyl)-5-(3,4-difluorophenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.701 nM	US-8969341: Pyrazolopyrrolidine compounds
3-[5-(3-chloro-2-fluorophenyl)-6-(4-chloro-2-methylphenyl)-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-2-yl]-4-methoxy-N-methylbenzamide	IC50	0.757 nM	US-9365576: Pyrrolopyrrolidinone compounds
(1S)-1-(4-chlorophenyl)-6-methoxy-2-[4-[methyl-[[4-(4-methyl-3-oxopiperazin-1-yl)cyclohexyl]methyl]amino]phenyl]-7-propan-2-yloxy-1,4-dihydroisoquinolin-3-one	IC50	0.8 nM	US-9051279: Substituted isoquinolinones and quinazolinones
4-[(6S)-5-(5-chloro-2-oxopiperidin-3-yl)-2-[2-(dimethylamino)-4-methoxypyrimidin-5-yl]-4-oxo-1-propan-2-yl-6H-pyrrolo[3,4-b]pyrrol-6-yl]benzonitrile	IC50	0.8 nM	US-9365576: Pyrrolopyrrolidinone compounds
5-(2-chloro-5-methoxy-4-pyridinyl)-4-(4-chloro-2-methylphenyl)-2-(2-methoxyphenyl)-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	0.926 nM	US-8969341: Pyrazolopyrrolidine compounds
4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-3-propan-2-yl-2-prop-2-enyl-4H-pyrrolo[3,4-c]pyrazol-6-one	IC50	1.1 nM	US-8969341: Pyrazolopyrrolidine compounds
methyl 2-[[4-(4-chloro-2-methylphenyl)-5-(5-chloro-2-methylphenyl)-6-oxo-3-propan-2-yl-4H-pyrrolo[3,4-c]pyrazol-2-yl]methyl]pyrrolidine-1-carboxylate	IC50	1.1 nM	US-8969341: Pyrazolopyrrolidine compounds
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	IC50	1.1 nM	US-8969341: Pyrazolopyrrolidine compounds
(1S)-1-(4-chlorophenyl)-6-methoxy-2-[5-[methyl-[[4-(4-oxo-3-propan-2-ylimidazolidin-1-yl)cyclohexyl]methyl]amino]-2-pyridinyl]-7-propan-2-yloxy-1,4-dihydroisoquinolin-3-one	IC50	1.2 nM	US-9051279: Substituted isoquinolinones and quinazolinones
5-(3-chloro-4-fluorophenyl)-4-(4-chlorophenyl)-4-(2-hydroxyethyl)-2-(2-methoxyphenyl)-3-propan-2-ylpyrrolo[3,4-c]pyrazol-6-one	IC50	1.3 nM	US-8969341: Pyrazolopyrrolidine compounds
(1S)-1-(4-chlorophenyl)-6-methoxy-2-[4-[methyl-[[4-(3-oxo-1,4-diazepan-1-yl)cyclohexyl]methyl]amino]phenyl]-7-propan-2-yloxy-1,4-dihydroisoquinolin-3-one	IC50	1.4 nM	US-9051279: Substituted isoquinolinones and quinazolinones

ChEMBL bioactivities

482 potent at pChembl≥5 of 719 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL5272028
9.68	IC50	0.21	nM	CHEMBL3657129
9.62	IC50	0.24	nM	CHEMBL5283210
9.10	Ki	0.8	nM	ABT 737
8.76	IC50	1.74	nM	CHEMBL5268205
8.70	Kd	2	nM	CHEMBL3347606
8.68	IC50	2.1	nM	CHEMBL4514512
8.64	Kd	2.3	nM	CHEMBL2381409
8.64	Kd	2.3	nM	CHEMBL4175039
8.62	Kd	2.4	nM	CHEMBL3347580
8.61	IC50	2.46	nM	CHEMBL5276426
8.52	IC50	3	nM	CHEMBL4068667
8.48	IC50	3.3	nM	CHEMBL4068667
8.43	IC50	3.74	nM	CHEMBL1352521
8.40	Kd	4	nM	CHEMBL3347578
8.34	IC50	4.6	nM	CHEMBL4065471
8.24	IC50	5.77	nM	CHEMBL5282600
8.22	IC50	6	nM	CHEMBL4095983
8.21	Kd	6.1	nM	CHEMBL502723
8.21	IC50	6.1	nM	CHEMBL4095983
8.17	Ki	6.8	nM	CHEMBL3621947
8.17	Ki	6.8	nM	CHEMBL5290323
8.16	Kd	6.9	nM	CHEMBL5394570
8.15	Ki	7	nM	CHEMBL5439046
8.15	Kd	7	nM	CHEMBL5439046
8.10	IC50	8	nM	CHEMBL5287696
8.07	Kd	8.5	nM	CHEMBL3347578
8.05	IC50	9	nM	CHEMBL5410760
8.03	IC50	9.3	nM	NUTLIN-3
8.00	Kd	10	nM	CHEMBL5592260
7.98	IC50	10.4	nM	CHEMBL4105199
7.97	IC50	10.7	nM	CHEMBL4095042
7.97	Ki	10.8	nM	CHEMBL5395366
7.96	IC50	11	nM	ALLICIN
7.94	IC50	11.4	nM	CHEMBL5267883
7.92	IC50	12.1	nM	CHEMBL4165669
7.91	IC50	12.42	nM	CHEMBL5284067
7.90	Ki	12.7	nM	CHEMBL5408686
7.89	Kd	12.9	nM	CHEMBL5271788
7.83	IC50	14.8	nM	CHEMBL5186444
7.80	Kd	16	nM	CHEMBL3347579
7.77	IC50	17	nM	CHEMBL5180980
7.77	IC50	17	nM	CHEMBL5280843
7.77	IC50	17	nM	CHEMBL3220312
7.74	IC50	18.3	nM	CHEMBL5199785
7.74	IC50	18.3	nM	CHEMBL2313487
7.73	Kd	18.5	nM	CHEMBL4075572
7.70	Kd	20	nM	CHEMBL5180980
7.70	IC50	20	nM	CHEMBL5593446
7.70	IC50	20	nM	CHEMBL2313487

PubChem BioAssay actives

340 with measured affinity, of 747 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
(3R,4S,5S,6R)-2-[4-(2,4-difluorophenyl)triazol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC 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	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC analysis	ic50	0.0002	uM
5-(5-chloro-1-methyl-2-oxo-3-pyridinyl)-4-(4-chlorophenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4H-pyrrolo[3,4-d]imidazol-6-one	1921010: Inhibition of human MDM4 by SRP assay	ic50	0.0002	uM
4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide	2074070: Binding affinity to MDM4/p53 interaction (unknown origin) assessed as inhibition constant	ki	0.0008	uM
(2S)-3-[4-(2,4-difluorophenyl)triazol-1-yl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC analysis	ic50	0.0017	uM
(1S)-6-methoxy-2-[4-[methyl-[[4-(4-methyl-3-oxopiperazin-1-yl)cyclohexyl]methyl]amino]phenyl]-1-phenyl-7-propan-2-yloxy-1,4-dihydroisoquinolin-3-one	1555414: Inhibition of MDMX (unknown origin)	ic50	0.0021	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(3S,6S,9S,12S,15S,18S,21S,28Z,33S)-33-[[(2S)-5-amino-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]carbamoyl]-18-(2-amino-2-oxoethyl)-9-(3-carbamimidamidopropyl)-12-(1H-indol-3-ylmethyl)-21,33-dimethyl-3,6,15-tris(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-28-en-21-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]pentanediamide	1350470: Binding affinity to full length human MDM4 by fluorescence polarization assay	kd	0.0023	uM
(2S)-2-acetamido-N-[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(3S,6S,9S,12S,15S,18S,21R,28Z,33S)-33-[[(2S)-5-amino-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]carbamoyl]-18-(2-amino-2-oxoethyl)-9-(4-carbamimidamidobutyl)-12-(1H-indol-3-ylmethyl)-21,33-dimethyl-3,6,15-tris(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-28-en-21-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]pentanediamide	746385: Binding affinity to human recombinant full length N-terminal his-tagged MDMX expressed in Escherichia coli BL21(DE3) by fluorescence polarization assay	kd	0.0023	uM
(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-phenyltriazol-1-yl)propanoic acid	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC analysis	ic50	0.0025	uM
(2S)-2-(3-phenylbutanoylamino)-3-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]propanoic acid	2117910: Inhibition of MDMX (unknown origin)	ic50	0.0030	uM
(2S)-3-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]-2-(3,3,3-triphenylpropanoylamino)propanoic acid	1452025: Inhibition of MDM4 in human SH-SY5Y cells assessed as reduction in MDM4 interaction with p53 after 10 mins by quantitative sandwich immune-enzymatic assay	ic50	0.0046	uM
(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[4-[(1S)-1-hydroxy-1-phenylethyl]triazol-1-yl]propanoic acid	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC analysis	ic50	0.0058	uM
(2S)-2-(3,3-diphenylpropanoylamino)-3-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]propanoic acid	2117910: Inhibition of MDMX (unknown origin)	ic50	0.0060	uM
3-[(2S,5S,8S,11S,14S,17S,20S,24E,32R)-32-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-20-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]-14-(3-amino-3-oxopropyl)-17-(cyclobutylmethyl)-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-11,20,32-trimethyl-3,6,9,12,15,18,33-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-24-en-2-yl]propanoic acid	1920980: Binding affinity to human MDM4 assessed as inhibition constant	ki	0.0068	uM
3-[(2S,5S,8S,11S,14S,17S,20S,24E,32R)-32-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-20-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]-14-(3-amino-3-oxopropyl)-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-11,20,32-trimethyl-17-(2-methylpropyl)-3,6,9,12,15,18,33-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-24-en-2-yl]propanoic acid	1997908: Binding affinity to 6x-His-TEV-tagged human MDMX (15 to 111 residues) assessed as dissociation constant by SPR analysis	kd	0.0069	uM
3-[(2S,5S,8S,11S,14S,17S,21Z,29R)-29-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-17-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]-14-(cyclobutylmethyl)-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-11,17,29-trimethyl-3,6,9,12,15,30-hexaoxo-1,4,7,10,13,16-hexazacyclotriacont-21-en-2-yl]propanoic acid	1997906: Binding affinity to 6x-His-TEV-tagged human MDMX (15 to 111 residues) assessed as inhibition constant by SPR analysis	ki	0.0070	uM
(1S)-1-(3-fluorophenyl)-1-[1-(phenylsulfanylmethyl)triazol-4-yl]ethanol	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC analysis	ic50	0.0080	uM
(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carboxylic acid	1464362: Inhibition of p53 binding to MDMX (unknown origin) after 30 mins by SPR analysis	kd	0.0085	uM
(1S,4R,13S,16S,19S,26S,29S,32S)-34-benzoyl-19-benzyl-16-(1H-indol-3-ylmethyl)-2,11,14,17,20,23,27,30-octaoxo-13,26-di(propan-2-yl)-29-[[3-(trifluoromethyl)phenyl]methyl]-3,7,8,9,12,15,18,21,24,28,31,34-dodecazatricyclo[30.2.1.16,9]hexatriaconta-6(36),7-diene-4-carboxamide	1968799: Inhibition of human MDM4 (1 to 116 residues) incubated for 1 hrs by fluorescence polarization assay	ic50	0.0090	uM
4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one	1908071: Inhibition of GST-tagged MDM4/Biotin-tagged p53 interaction (unknown origin) incubated for 40 mins by TR-FRET assay	ic50	0.0093	uM
8-[(4S,5R)-4,5-bis(4-chlorophenyl)-1-(3-oxopiperazine-1-carbonyl)-4,5-dihydroimidazol-2-yl]-1-phenyl-3,4-dihydro-1,4-benzodiazepine-2,5-dione	2117903: Binding affinity to N-terminal human MDMX (22 to 110 residues) extracted from Escherichia coli BL21 (DE3) assessed as dissociation constant	kd	0.0100	uM
methyl (2S)-3-(4-hydroxyphenyl)-2-(3,3,3-triphenylpropanoylamino)propanoate	1452025: Inhibition of MDM4 in human SH-SY5Y cells assessed as reduction in MDM4 interaction with p53 after 10 mins by quantitative sandwich immune-enzymatic assay	ic50	0.0104	uM
(2S)-3-(4-chlorophenyl)-2-(3,3-diphenylpropanoylamino)propanoic acid	1452025: Inhibition of MDM4 in human SH-SY5Y cells assessed as reduction in MDM4 interaction with p53 after 10 mins by quantitative sandwich immune-enzymatic assay	ic50	0.0107	uM
7-[(4S,5R)-4,5-bis(4-chlorophenyl)-1-(3-oxopiperazine-1-carbonyl)-4,5-dihydroimidazol-2-yl]-1-phenyl-3,4-dihydro-1,4-benzodiazepine-2,5-dione	2024721: Binding affinity to MDM4/p53 (unknown origin) assessed as inhibition constant by FP assay	ki	0.0108	uM
3-prop-2-enylsulfinylsulfanylprop-1-ene	2074071: Inhibition of MDM4/p53 (unknown origin)	ic50	0.0110	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-6-amino-2-[[(2R)-2-[[(2S)-4-amino-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-4-oxobutanoyl]amino]-3-sulfanylpropanoyl]amino]hexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-amino-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1920984: Inhibition of human MDM4/p53 interaction by SPR analysis	ic50	0.0114	uM
(3S)-3-[[2-[[3-(diaminomethylideneamino)benzoyl]amino]acetyl]amino]-4-oxo-4-[[(1R)-1-phenylethyl]amino]butanoic acid	1350413: Displacement of p53 from MDM4 in human SHSY-5Y cells incubated for 10 mins by sandwich ELISA method	ic50	0.0121	uM
1-[(2R,4S,5S)-4-[4-[(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC analysis	ic50	0.0124	uM
(2S,5S,8S,11S,14S,17S,20S,24E,32R)-32-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]-14-(3-amino-3-oxopropyl)-5-[(4-hydroxyphenyl)methyl]-2-(1H-imidazol-5-ylmethyl)-8-(1H-indol-3-ylmethyl)-11,20,32-trimethyl-17-(2-methylpropyl)-3,6,9,12,15,18,33-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-24-ene-20-carboxamide	1997906: Binding affinity to 6x-His-TEV-tagged human MDMX (15 to 111 residues) assessed as inhibition constant by SPR analysis	ki	0.0127	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-5-amino-5-oxopentanoyl]amino]-5-[[(2S,3R)-1-[[(2S)-1-[[(3S,6S,9S,12S,15S,18S,21R,28Z,33S)-9-(4-aminobutyl)-33-[[(2S)-4-carboxy-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxobutan-2-yl]carbamoyl]-18-(carboxymethyl)-12-(1H-indol-3-ylmethyl)-21,33-dimethyl-3,6,15-tris(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-28-en-21-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1920987: Binding affinity to human MDM4 assessed as dissociation constant by FP assay	kd	0.0129	uM
ethyl 6-chloro-4’-(3-chloro-2-fluorophenyl)-1’-cyclohexyl-2-oxospiro[1H-indole-3,5’-4H-pyrazole]-3’-carboxylate	1855505: Inhibition of MDM4/p53 interaction in human SH-SY5Y cells preincubated for 10 mins under shaking condition and measured after 1.5 hrs by immuno-enzymatic assay	ic50	0.0148	uM
2-[5-[(Z)-(6-chloro-7-methylindol-3-ylidene)methyl]-4-hydroxy-2-oxo-1H-imidazol-3-yl]-2-(3,4-difluorophenyl)-N-(1,3-dihydroxypropan-2-yl)acetamide	2117910: Inhibition of MDMX (unknown origin)	ic50	0.0170	uM
3-[[6-chloro-3-[3-[(1S)-1-(3-chlorophenyl)ethyl]-5-phenylimidazol-4-yl]-1H-indole-2-carbonyl]amino]-4-[4-(2-oxo-1,3-oxazinan-3-yl)piperidin-1-yl]benzoic acid	1921008: Inhibition of human MDM4 by TR-FRET assay	ic50	0.0170	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	1908067: Inhibition of human MDM4 by TR-FRET assay	ic50	0.0170	uM
5-[[2-[1-(benzenesulfonyl)pyrrol-3-yl]-1H-indol-3-yl]methyl]-2,3-dimethoxyphenol	1855506: Inhibition of MDM4 (unknown origin)	ic50	0.0183	uM
2-[1-(benzenesulfonyl)pyrrol-3-yl]-3-[(3,4,5-trimethoxyphenyl)methyl]-1H-indole	1908068: Inhibition of MDM4/p53 interaction in human SH-SY5Y cells using TMB as substrate incubated for 10 mins by quantitative immuno-enzymatic assay	ic50	0.0183	uM
(2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carboxylic acid	1464362: Inhibition of p53 binding to MDMX (unknown origin) after 30 mins by SPR analysis	kd	0.0185	uM
ethyl (3R,4’R)-6-chloro-4’-(3-chloro-2-fluorophenyl)-1’-cyclohexyl-2-oxospiro[1H-indole-3,5’-4H-pyrazole]-3’-carboxylate	2117910: Inhibition of MDMX (unknown origin)	ic50	0.0200	uM
(2S)-1-[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carboxylic acid	1464362: Inhibition of p53 binding to MDMX (unknown origin) after 30 mins by SPR analysis	kd	0.0214	uM
N-[(3S,4R,5R,6R)-2-[4-[(1S)-1-(3-fluorophenyl)-1-hydroxyethyl]triazol-1-yl]-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-3-yl]acetamide	1928057: Inhibition of human DMX-p53 protein-protein interaction by ITC analysis	ic50	0.0224	uM
methyl (2S)-2-(3,3-diphenylpropanoylamino)-3-(4-hydroxyphenyl)propanoate	1452025: Inhibition of MDM4 in human SH-SY5Y cells assessed as reduction in MDM4 interaction with p53 after 10 mins by quantitative sandwich immune-enzymatic assay	ic50	0.0228	uM
2-[5-[(Z)-(6-chloro-7-methylindol-2-ylidene)methyl]-4-hydroxy-2-oxo-1H-imidazol-3-yl]-2-(3,4-difluorophenyl)-N-(1,3-dihydroxypropan-2-yl)acetamide	1855506: Inhibition of MDM4 (unknown origin)	ic50	0.0247	uM
(2S,5S,8S,11S,14S,17S,20S,24E,32R)-32-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-14-(3-amino-3-oxopropyl)-5-[(4-hydroxyphenyl)methyl]-8-(1H-indol-3-ylmethyl)-2,11,20,32-tetramethyl-17-(2-methylpropyl)-3,6,9,12,15,18,33-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-24-ene-20-carboxamide	1920993: Binding affinity to human MDM4 assessed as inhibition constant by fluorescence based assay	ki	0.0247	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-5-amino-5-oxopentanoyl]amino]-5-[[(2S,3R)-1-[[(2S)-1-[[(3S,6S,9S,12S,15S,18S,21R,28Z,33S)-9-(4-aminobutyl)-33-[[(2S)-4-carboxy-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxobutan-2-yl]carbamoyl]-3-(2-carboxyethyl)-18-(carboxymethyl)-12-(1H-indol-3-ylmethyl)-21,33-dimethyl-6,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotritriacont-28-en-21-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	1920989: Binding affinity to human MDM4 assessed as dissociation constant	kd	0.0247	uM
4-[(4S,5R)-2-[4-(3-amino-3-oxopropanoyl)-2-[(2-methylpropan-2-yl)oxy]phenyl]-5-(5-chloro-1H-indol-3-yl)-1-(3-oxopiperazine-1-carbonyl)-4,5-dihydroimidazol-4-yl]benzoic acid	1855506: Inhibition of MDM4 (unknown origin)	ic50	0.0270	uM
4-[(4S,5R)-2-[4-(3-amino-3-oxopropanoyl)-2-[(2-methylpropan-2-yl)oxy]phenyl]-5-(1H-indol-3-yl)-1-(3-oxopiperazine-1-carbonyl)-4,5-dihydroimidazol-4-yl]benzoic acid	1921001: Inhibition of human his-tagged MDM4 assessed as dissociation constant by ITC assay	kd	0.0270	uM
(3S,6S,9S,12S,15S,18R,21S,24S,27S,30R)-3-benzyl-9-tert-butyl-6-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-27-(2-methoxyethyl)-4,15,16,18,19,24,25-heptamethyl-21-(1,3-thiazol-4-ylmethyl)-1,4,7,10,13,16,19,22,25,28-decazabicyclo[28.3.0]tritriacontane-2,5,8,11,14,17,20,23,26,29-decone	2015548: Inhibition of N-terminal biotin-his-tagged MDMX (24 to 108 residues)(unknown origin) binding to p53 incubated for 1 hr by Alphascreen assay	ic50	0.0300	uM
(3S,6S,9S,12S,15S,18R,21S,24S,30R)-3-benzyl-9-tert-butyl-6-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-4,15,16,18,19,24,25-heptamethyl-21-(1,3-thiazol-4-ylmethyl)-1,4,7,10,13,16,19,22,25,28-decazabicyclo[28.3.0]tritriacontane-2,5,8,11,14,17,20,23,26,29-decone	2117910: Inhibition of MDMX (unknown origin)	ic50	0.0300	uM
(3E)-3-[(3-chlorophenyl)methylidene]-1-(3-chlorophenyl)sulfonylindol-2-one	1980397: Binding affinity to MDM4/p53 interaction (unknown origin) assessed as inhibition constant	ki	0.0310	uM
[2-(1H-pyrrol-3-yl)-1H-indol-3-yl]-(3,4,5-trimethoxyphenyl)methanol	2117910: Inhibition of MDMX (unknown origin)	ic50	0.0400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
Cyclosporine	increases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
methacrylaldehyde	affects cotreatment, affects expression, increases expression, increases abundance	2
Acrolein	affects cotreatment, affects expression, increases expression, increases abundance	2
Copper	affects binding, increases expression	2
Ozone	affects cotreatment, affects expression, increases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
GSK3235025	affects expression, affects splicing	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
naringenin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
deoxynivalenol	increases expression	1
5’-methylthioadenosine	affects expression, affects splicing	1
trichostatin A	affects expression	1
beta-lapachone	increases expression, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
nickel chloride	decreases expression	1
leptomycin B	affects cotreatment, decreases expression	1
arsenic disulfide	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
cylindrospermopsin	increases expression	1
hexabromocyclododecane	decreases expression, increases expression	1
CGP 52608	affects binding, increases reaction	1
platycodin D	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

149 unique, capped per target: 148 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1068494	Binding	Inhibition of GST-tagged HDMX expressed in Escherichia coli BL21 (DE3) assessed as inhibition of HDMX binding to p53 protein by fluorescence anisotropy competition method	N-acylpolyamine inhibitors of HDM2 and HDMX binding to p53. — Bioorg Med Chem
CHEMBL1738436	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of Inhibitors of Mdm2/MdmX interaction in luminescent format. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID485346, AID488776]	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1049	647V	Cancer cell line	Male
CVCL_A666	RO-H85-1	Cancer cell line	Male
CVCL_A9SX	BL1391	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00774527	PHASE3	COMPLETED	Comparison of Cy-Atg Vs Cy-Flu-Atg for the Conditioning Therapy in Allo-HCT
NCT02393508	PHASE3	UNKNOWN	The Impact of Red Cell Age on Product Utilization in the Chronically Transfused Outpatient Population
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT01050439	PHASE2	TERMINATED	Unrelated Donor Transplant for Malignant and Non-Malignant Disorders
NCT01596699	PHASE2	TERMINATED	Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
NCT01757145	PHASE2	UNKNOWN	Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation
NCT02224872	PHASE2	COMPLETED	Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia
NCT02277639	PHASE2	COMPLETED	Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases
NCT02349906	PHASE2	COMPLETED	Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases
NCT02722668	PHASE2	COMPLETED	UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep
NCT04356469	PHASE2	RECRUITING	TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children
NCT04558736	PHASE2	RECRUITING	Haploidentical HCT for Severe Aplastic Anemia
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT07585136	PHASE1	NOT_YET_RECRUITING	Stem Cell Mobilization and Apheresis for Life-threatening Blood Disorders
NCT01419704	PHASE1/PHASE2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02055456	PHASE1/PHASE2	COMPLETED	Nandrolone Decanoate in the Treatment of Telomeropathies
NCT02337595	PHASE1/PHASE2	COMPLETED	Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation
NCT03128996	PHASE1/PHASE2	RECRUITING	Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT02356653	EARLY_PHASE1	RECRUITING	Expanded Access Protocol Using CD3+/CD19+ Depleted PBSC
NCT02928991	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Fludarabine Based RIC for Bone Marrow Failure Syndromes
NCT06787560	EARLY_PHASE1	RECRUITING	CD7 CAR-T Cell Sequential Allo-HSCT for Non-malignant Blood and Immune System Diseases
NCT00315419	Not specified	UNKNOWN	Identifying Characteristics of Bone Marrow Failure Syndromes
NCT00897260	Not specified	COMPLETED	Umbilical Cord Blood Transplantation As Treatment Of Adult Patients With Hematologic Disorders
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03145545	Not specified	AVAILABLE	Expanded Access Protocol Using Alpha/Beta T and CD19+ Depleted PBSC
NCT04781790	Not specified	RECRUITING	French National Registry of Bone Marrow Failures
NCT04819607	Not specified	UNKNOWN	The Evaluating Multidisciplinary Bone Marrow Failure Care in Bone Marrow Failure and Related Disorders.
NCT05236764	Not specified	ACTIVE_NOT_RECRUITING	Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion
NCT07535372	Not specified	NOT_YET_RECRUITING	ASO Treatment for Syndromic Craniosynostoses