Cushing disease due to pituitary adenoma

Summary

Cushing disease due to pituitary adenoma (MONDO:0009050) is a cancer with 4 cohort genes (3 CIViC-evidence somatic drivers; 14 ClinVar predisposition records) and 41 clinical trials. Top therapeutic interventions include pasireotide, cabergoline, and mifepristone.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 14
• Phenotypes (HPO): 64
• Clinical trials: 41

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	4	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.2	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

64 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0003118	Increased circulating cortisol level	Very frequent (80-99%)
HP:0003466	Paradoxical increased cortisol secretion on dexamethasone suppression test	Very frequent (80-99%)
HP:0008291	Pituitary corticotropic cell adenoma	Very frequent (80-99%)
HP:0012030	Increased urinary cortisol level	Very frequent (80-99%)
HP:0000939	Osteoporosis	Frequent (30-79%)
HP:0000953	Hyperpigmentation of the skin	Frequent (30-79%)
HP:0000963	Thin skin	Frequent (30-79%)
HP:0000978	Bruising susceptibility	Frequent (30-79%)
HP:0001007	Hirsutism	Frequent (30-79%)
HP:0001050	Plethora	Frequent (30-79%)
HP:0001058	Poor wound healing	Frequent (30-79%)
HP:0001061	Acne	Frequent (30-79%)
HP:0001065	Striae distensae	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001626	Abnormality of the cardiovascular system	Frequent (30-79%)
HP:0001888	Lymphopenia	Frequent (30-79%)
HP:0001956	Truncal obesity	Frequent (30-79%)
HP:0001974	Leukocytosis	Frequent (30-79%)
HP:0002721	Immunodeficiency	Frequent (30-79%)
HP:0003154	Increased circulating ACTH level	Frequent (30-79%)
HP:0004324	Increased body weight	Frequent (30-79%)
HP:0007126	Proximal amyotrophy	Frequent (30-79%)
HP:0008221	Adrenal hyperplasia	Frequent (30-79%)
HP:0010284	Intra-oral hyperpigmentation	Frequent (30-79%)
HP:0012743	Abdominal obesity	Frequent (30-79%)
HP:0025017	Capillary fragility	Frequent (30-79%)
HP:0025383	Dorsocervical fat pad	Frequent (30-79%)
HP:0000141	Amenorrhea	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000712	Emotional lability	Frequent (30-79%)
HP:0000819	Diabetes mellitus	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0031891	Decreased eosinophil count	Frequent (30-79%)
HP:0040270	Impaired glucose tolerance	Frequent (30-79%)
HP:0500011	Moon facies	Frequent (30-79%)
HP:0030200	Fatiguable weakness of proximal limb muscles	Frequent (30-79%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000725	Psychotic episodes	Occasional (5-29%)
HP:0000869	Secondary amenorrhea	Occasional (5-29%)
HP:0000876	Oligomenorrhea	Occasional (5-29%)
HP:0000979	Purpura	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001658	Myocardial infarction	Occasional (5-29%)
HP:0002086	Abnormality of the respiratory system	Occasional (5-29%)
HP:0002209	Sparse scalp hair	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0002690	Large sella turcica	Occasional (5-29%)
HP:0002953	Vertebral compression fracture	Occasional (5-29%)
HP:0011370	Recurrent cutaneous fungal infections	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Cushing disease due to pituitary adenoma
Mondo ID	MONDO:0009050
MeSH	D049913
OMIM	219090
Orphanet	96253
DOID	DOID:7004
ICD-11	380861892
NCIT	C113210
SNOMED CT	254958004
UMLS	C0221406
MedGen	66381
GARD	0012867
MedDRA	10035109
Is cancer (heuristic)	yes

Also known as: ACTH producing pituitary adenoma · corticotroph adenoma · corticotroph pituitary adenoma · Cushing disease · Cushing disease, pituitary · Cushing’s disease · PITA4 · pituitary adenoma 4, ACTH-secreting · pituitary adenoma 4, ACTH-secreting, somatic · pituitary adenoma, ACTH-secreting · pituitary corticotroph micro-adenoma · pituitary dependent Cushing syndrome · pituitary-dependent Cushing syndrome

Data availability: 14 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › endocrine gland neoplasm › pituitary tumor › functioning pituitary gland neoplasm › functioning pituitary gland adenoma › Cushing disease due to pituitary adenoma

Related subtypes (4): TSH producing pituitary tumor, Nelson syndrome, mixed functioning pituitary adenoma, functioning gonadotropic adenoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

14 retrieved; paginated sample, class counts are floors:

6 pathogenic, 3 uncertain significance, 3 conflicting classifications of pathogenicity, 1 likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
161994	NM_005154.3(USP8):c.[2138T>G;2150A>G]		Pathogenic	no assertion criteria provided
15905	NM_002070.4(GNAI2):c.535C>G (p.Arg179Gly)	GNAI2	Pathogenic	no assertion criteria provided
161991	NM_005154.5(USP8):c.2152TCC[1] (p.Ser719del)	USP8	Pathogenic	no assertion criteria provided
161992	NM_005154.5(USP8):c.2152T>C (p.Ser718Pro)	USP8	Pathogenic	no assertion criteria provided
161993	NM_005154.5(USP8):c.2153C>G (p.Ser718Cys)	USP8	Pathogenic	no assertion criteria provided
161995	NM_005154.5(USP8):c.2159C>G (p.Pro720Arg)	USP8	Pathogenic	no assertion criteria provided
485052	NM_003977.4(AIP):c.26G>A (p.Arg9Gln)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485056	NM_003977.4(AIP):c.827C>T (p.Ala276Val)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4893	NM_003977.4(AIP):c.911G>A (p.Arg304Gln)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485072	NM_003977.4(AIP):c.355C>T (p.Arg119Trp)	AIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
824564	NM_003977.4(AIP):c.406G>T (p.Ala136Ser)	AIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1379085	NM_005154.5(USP8):c.2108C>A (p.Pro703His)	USP8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1117565	NM_003977.4(AIP):c.792C>T (p.Asn264=)	AIP	Likely benign	criteria provided, multiple submitters, no conflicts
548911	NM_001370259.2(MEN1):c.913-42G>C	MEN1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 15 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
USP8	Act	HCC,LUSC,PCM
GNAI2	Act	NHL	CIViC #2312
MEN1	LoF	ACC,BLCA,BRCA,HCC,LUNG,PANCREAS,PANET,WDTC	CIViC #3485

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
USP8	Orphanet:401795	Autosomal recessive spastic paraplegia type 59
USP8	Orphanet:96253	Cushing disease
AIP	Orphanet:2965	Prolactinoma
AIP	Orphanet:314777	Familial isolated pituitary adenoma
AIP	Orphanet:314786	Silent pituitary adenoma
AIP	Orphanet:314790	Null pituitary adenoma
AIP	Orphanet:963	Acromegaly
AIP	Orphanet:99725	Pituitary gigantism
MEN1	Orphanet:2965	Prolactinoma
MEN1	Orphanet:314786	Silent pituitary adenoma
MEN1	Orphanet:314790	Null pituitary adenoma
MEN1	Orphanet:652	Multiple endocrine neoplasia type 1
MEN1	Orphanet:97279	Insulinoma
MEN1	Orphanet:99725	Pituitary gigantism
MEN1	Orphanet:99879	Familial isolated hyperparathyroidism

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
USP8	HGNC:12631	ENSG00000138592	P40818	Ubiquitin carboxyl-terminal hydrolase 8	clinvar
AIP	HGNC:358	ENSG00000110711	O00170	AH receptor-interacting protein	clinvar
GNAI2	HGNC:4385	ENSG00000114353	P04899	Guanine nucleotide-binding protein G(i) subunit alpha-2	clinvar
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
USP8	Ubiquitin carboxyl-terminal hydrolase 8	Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation.
AIP	AH receptor-interacting protein	May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.
GNAI2	Guanine nucleotide-binding protein G(i) subunit alpha-2	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.
MEN1	Menin	Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	9.2×	0.210
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
USP8	Protease	yes	3.4.19.12	Peptidase_C19_UCH, Rhodanese-like_dom, USP8_dimer
AIP	Other/Unknown	no		PPIase_FKBP_dom, TPR-like_helical_dom_sf, TPR_rpt
GNAI2	Other/Unknown	no		Gprotein_alpha_su, Gprotein_alpha_I, GproteinA_insert
MEN1	Other/Unknown	no		Menin

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	3
calcaneal tendon	1
colonic epithelium	1
sural nerve	1
popliteal artery	1
tibial artery	1
monocyte	1
right lung	1
lower esophagus mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
USP8	284	ubiquitous	marker	calcaneal tendon, sural nerve, colonic epithelium
AIP	241	ubiquitous	marker	granulocyte, popliteal artery, tibial artery
GNAI2	291	ubiquitous	marker	granulocyte, monocyte, right lung
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEN1	5,226
GNAI2	3,311
USP8	2,737
AIP	1,268

Intra-cohort edges

A	B	Sources
AIP	MEN1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEN1	O00255	69
GNAI2	P04899	34
USP8	P40818	9
AIP	O00170	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Aryl hydrocarbon receptor signalling	1	475.8×	0.043	AIP
Downregulation of ERBB2:ERBB3 signaling	1	203.9×	0.043	USP8
Adenylate cyclase inhibitory pathway	1	190.3×	0.043	GNAI2
Regulation of FZD by ubiquitination	1	129.8×	0.043	USP8
Negative regulation of MET activity	1	129.8×	0.043	USP8
ADP signalling through P2Y purinoceptor 12	1	124.1×	0.043	GNAI2
Interleukin-12 family signaling	1	119.0×	0.043	AIP
Interleukin-12 signaling	1	102.0×	0.043	AIP
Adrenaline,noradrenaline inhibits insulin secretion	1	98.5×	0.043	GNAI2
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	92.1×	0.043	MEN1
RHO GTPases activate IQGAPs	1	86.5×	0.043	MEN1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	77.2×	0.043	MEN1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	75.1×	0.043	AIP
Formation of WDR5-containing histone-modifying complexes	1	66.4×	0.043	MEN1
ADORA2B mediated anti-inflammatory cytokines production	1	63.4×	0.043	GNAI2
GPER1 signaling	1	62.1×	0.043	GNAI2
Deactivation of the beta-catenin transactivating complex	1	58.3×	0.043	MEN1
G alpha (z) signalling events	1	58.3×	0.043	GNAI2
Phase I - Functionalization of compounds	1	54.9×	0.043	AIP
Regulation of insulin secretion	1	54.9×	0.043	GNAI2
Signaling by TGF-beta Receptor Complex	1	50.1×	0.045	MEN1
Extra-nuclear estrogen signaling	1	42.6×	0.051	GNAI2
Epigenetic regulation by WDR5-containing histone modifying complexes	1	38.6×	0.054	MEN1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	36.6×	0.054	MEN1
Biological oxidations	1	32.4×	0.058	AIP
Formation of the beta-catenin:TCF transactivating complex	1	30.1×	0.058	MEN1
TCF dependent signaling in response to WNT	1	29.4×	0.058	MEN1
Signaling by TGFB family members	1	28.8×	0.058	MEN1
Signaling by WNT	1	28.0×	0.058	MEN1
Post-translational protein phosphorylation	1	25.0×	0.063	MEN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of protein catabolic process at postsynapse, modulating synaptic transmission	1	1053.2×	0.016	USP8
negative regulation of lysosomal protein catabolic process	1	842.6×	0.016	USP8
positive regulation of amyloid fibril formation	1	842.6×	0.016	USP8
G protein-coupled adenosine receptor signaling pathway	1	601.9×	0.016	GNAI2
negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway	1	601.9×	0.016	GNAI2
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	526.6×	0.016	MEN1
T-helper 2 cell differentiation	1	468.1×	0.016	MEN1
negative regulation of calcium ion-dependent exocytosis	1	468.1×	0.016	GNAI2
negative regulation of synaptic transmission	1	421.3×	0.016	GNAI2
negative regulation of adenylate cyclase activity	1	351.1×	0.017	GNAI2
positive regulation of urine volume	1	324.1×	0.017	GNAI2
G protein-coupled acetylcholine receptor signaling pathway	1	263.3×	0.017	GNAI2
osteoblast development	1	247.8×	0.017	MEN1
positive regulation of superoxide anion generation	1	221.7×	0.017	GNAI2
regulation of calcium ion transport	1	200.6×	0.017	GNAI2
positive regulation of neural precursor cell proliferation	1	191.5×	0.017	GNAI2
obsolete negative regulation of DNA-binding transcription factor activity	1	183.2×	0.017	MEN1
protein K48-linked deubiquitination	1	162.0×	0.017	USP8
protein K63-linked deubiquitination	1	156.0×	0.017	USP8
negative regulation of protein phosphorylation	1	145.3×	0.017	MEN1
obsolete protein targeting to mitochondrion	1	145.3×	0.017	AIP
response to gamma radiation	1	145.3×	0.017	MEN1
cellular response to dexamethasone stimulus	1	145.3×	0.017	USP8
negative regulation of JNK cascade	1	140.4×	0.017	MEN1
negative regulation of apoptotic signaling pathway	1	140.4×	0.017	GNAI2
gamma-aminobutyric acid signaling pathway	1	135.9×	0.017	GNAI2
positive regulation of transforming growth factor beta receptor signaling pathway	1	131.7×	0.017	MEN1
cellular response to nerve growth factor stimulus	1	117.0×	0.019	USP8
positive regulation of vascular associated smooth muscle cell proliferation	1	108.0×	0.019	GNAI2
transcription initiation-coupled chromatin remodeling	1	95.8×	0.021	MEN1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 1

Druggability breadth: 4 of 4 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MEN1	LOPERAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
GNAI2	2	3
AIP	1	2
USP8	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1
PROTRIPTYLINE HYDROCHLORIDE	4	MEN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MEN1	93	Binding:86, Functional:7
USP8	54	Binding:51, Functional:3
AIP	10	Binding:10
GNAI2	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
USP8	3.4.19.12	ubiquitinyl hydrolase 1

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

29 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1
PROTRIPTYLINE HYDROCHLORIDE	4	MEN1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MEN1
B	Phased (≥1) drug, not yet approved	2	AIP, GNAI2
C	Druggable family + PDB, no drug	1	USP8
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
USP8	54	—

Clinical trials & evidence

Clinical trials

Clinical trials: 41.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	19
PHASE3	8
PHASE2	8
PHASE4	3
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01794793	PHASE4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT02060383	PHASE4	COMPLETED	Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing’s Disease or Acromegaly
NCT03080181	PHASE4	COMPLETED	Adipokine Profile in Patients With Cushing’s Disease on Pasireotide Treatment
NCT00434148	PHASE3	COMPLETED	Safety and Efficacy of Different Dose Levels of Pasireotide in Patients With de Novo, Persistent or Recurrent Cushing’s Disease
NCT00889525	PHASE3	COMPLETED	Study of Cabergoline in Treatment of Corticotroph Pituitary Tumor
NCT01371565	PHASE3	COMPLETED	Compassionate Use of CORLUX® (Mifepristone) in the Treatment of Signs and Symptoms of Endogenous Cushing’s Syndrome
NCT01374906	PHASE3	COMPLETED	Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing’s Disease
NCT01582061	PHASE3	COMPLETED	An Open-label, Multi-center, Expanded Access Study of Pasireotide s.c. in Patients With Cushing’s Disease.
NCT01925092	PHASE3	WITHDRAWN	Mifepristone in Children With Refractory Cushing’s Disease
NCT02697734	PHASE3	COMPLETED	Efficacy and Safety Evaluation of Osilodrostat in Cushing’s Disease
NCT03621280	PHASE3	COMPLETED	Open-label Treatment in Cushing’s Syndrome
NCT03774446	PHASE2	RECRUITING	Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease
NCT05804669	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing’s Syndrome
NCT05971758	PHASE2	RECRUITING	Fimepinostat, Combination HDAC and Pi3-kinase Inhibitor Tumor-Directed Therapy for Cushing Disease
NCT06471829	PHASE2	RECRUITING	A Trial of Lu AG13909 in Adult Participants With Cushing’s Disease
NCT00171951	PHASE2	COMPLETED	Extension Study to Assess the Safety and Efficacy of Pasireotide in Participants With Cushing’s Disease
NCT00612066	PHASE2	TERMINATED	Rosiglitazone in Treating Patients With Newly Diagnosed ACTH-Secreting Pituitary Tumor (Cushing Disease)
NCT00845351	PHASE1/PHASE2	UNKNOWN	Preoperative Bexarotene Treatment for Cushing’s Disease
NCT01331239	PHASE2	COMPLETED	Safety and Efficacy of LCI699 in Cushing’s Disease Patients
NCT02484755	PHASE2	UNKNOWN	Targeted Therapy With Gefitinib in Patients With USP8-mutated Cushing’s Disease
NCT04339751	PHASE2	WITHDRAWN	Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease
NCT07460232	EARLY_PHASE1	RECRUITING	FET PET/CT Imaging To Localize Pituitary Adenomas In Cushing Disease
NCT00001595	Not specified	RECRUITING	An Investigation of Pituitary Tumors and Related Hypothalmic Disorders
NCT03364803	Not specified	RECRUITING	Collecting Information About Treatment Results for Patients With Cushing’s Syndrome
NCT03831958	Not specified	RECRUITING	Long-Term Follow-Up of Survivors of Pediatric Cushing Disease
NCT03974789	Not specified	ACTIVE_NOT_RECRUITING	Discriminant Capacity and Thresholds of Salivary Cortisol in Chemiluminescence in the Diagnosis of Hypercorticisms
NCT04486859	Not specified	ACTIVE_NOT_RECRUITING	Postoperative Thrombosis Prevention in Patients With CD
NCT04569591	Not specified	RECRUITING	DDAVP for Pituitary Adenoma
NCT07108244	Not specified	ENROLLING_BY_INVITATION	Use of [18F]FET PET-MRI to Improve Detection of Pituitary Adenomas in Cushing’s Disease
NCT07335315	Not specified	RECRUITING	Evaluation of Intraoperative Contrast Enhanced Ultrasound for the Identification of Pituitary Adenoma in Cushing’s Disease Compared to Other Pituitary Tumors
NCT07463625	Not specified	RECRUITING	Evaluation of Positron Emission Tomography (PET) With [18F]FET for the Detection of ACTH-Secreting Corticotroph Pituitary Neuroendocrine Tumors.
NCT00881283	Not specified	TERMINATED	Long-term Cardiovascular Risk in Cured Cushing’s Patients
NCT02233335	Not specified	COMPLETED	The Factors Associated With the Recurrence in Patients With Cushing Disease
NCT02350153	Not specified	COMPLETED	Cushing´s Disease Epidemiology in Sweden
NCT02568982	Not specified	COMPLETED	Cushing’s Disease Complications
NCT02603653	Not specified	COMPLETED	Assessment of Persistent Cognitive Impairment After Cure of Cushing’s Disease
NCT03297892	Not specified	UNKNOWN	Health Status of the Patients Followed for a Disease of Cushing in the Region Large-West of 1990 to 2015
NCT03346954	Not specified	COMPLETED	Impact of [11C]-Methionine PET/MRI in the Detection of Pituitary Adenomas Secreting ACTH and Causing Cushing’s Disease
NCT03474601	Not specified	UNKNOWN	Seoul National University Pituitary Disease Cohort Study
NCT04201444	Not specified	COMPLETED	Hair Cortisol and Cushing’s Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PASIREOTIDE	4	6
CABERGOLINE	4	2
MIFEPRISTONE	4	2
OSILODROSTAT	4	2
BEXAROTENE	4	1
DESMOPRESSIN ACETATE	4	1
INSULIN HUMAN	4	1
LEVOKETOCONAZOLE	4	1
LIRAGLUTIDE	4	1
SITAGLIPTIN	4	1
ATUMELNANT	2	1
FIMEPINOSTAT	2	1
SELICICLIB	2	1
CHEMBL4593105	0	2
CHEMBL5192470	0	2
CHEMBL3185489	0	1
CHEMBL439305	0	1
CHEMBL4524066	0	1
CHEMBL4645029	0	1
CHEMBL4785366	0	1
CHEMBL5219405	0	1
CHEMBL5275397	0	1
CHEMBL5287934	0	1
CHEMBL5405257	0	1