Osilodrostat

Summary

Osilodrostat (CHEMBL3099695) is an approved small molecule (ATC H02CA02) targeting CYP11B1 and CYP11B2; indicated across 8 conditions including adrenal gland disorder and acth-dependent cushing syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: H02CA02
• Targets: 2 (CYP11B1, CYP11B2)
• Indications: 8 conditions
• Clinical trials: 20
• Chemistry: 227.24 Da · C13H10FN3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3099695
Name	Osilodrostat
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	44139752
ATC	H02CA02
Molecular formula	C13H10FN3
Molecular weight	227.24
InChIKey	USUZGMWDZDXMDG-CYBMUJFWSA-N

SMILES: C1CC2=CN=CN2[C@H]1C3=C(C=C(C=C3)C#N)F

IUPAC name: 4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile

Also known as: Lci-699, Lci699, Osilodrostat, OSILODROSTAT, osilodrostat

Parent form; salt/anhydrous children: CHEMBL3707393

Patent coverage: 126 distinct patent families (347 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 342 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CYP11B1	CYP11B1	Inhibition	8.54	0.1%	P15538
CYP11B2	CYP11B2	Inhibition	9.7	0.7%	P19099

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Cytochrome P450 11B1, mitochondrial, Aromatase, Histamine H1 receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Cytochrome P450 11B2, mitochondrial, Cytochrome P450 11B2, mitochondrial, Steroid 17-alpha-hydroxylase/17,20 lyase, Cytochrome P450 11B2, mitochondrial, Cytochrome P450 11B1, mitochondrial.

Bioactivity

ChEMBL activities: 31 potent at pChembl ≥ 5 of 32 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP11B2	9.7	IC50	0.2	nM	CHEMBL_ACT_14730179
CYP11B2	9.7	IC50	0.2	nM	CHEMBL_ACT_14730263
CYP11B2	9.7	IC50	0.2	nM	CHEMBL_ACT_15030753
CYP11B2	9.7	IC50	0.2	nM	CHEMBL_ACT_15157354
CYP11B2	9.7	IC50	0.2	nM	CHEMBL_ACT_15211512
CYP11B2	9.7	IC50	0.2	nM	CHEMBL_ACT_18078753
CYP11B2	9.3	IC50	0.5	nM	CHEMBL_ACT_24783369
CYP11B2	9.15	IC50	0.7	nM	CHEMBL_ACT_13862714
CYP11B2	9.15	IC50	0.7	nM	CHEMBL_ACT_16422884
CYP11B2	9.15	IC50	0.7	nM	CHEMBL_ACT_25500511
CYP11B2	8.92	IC50	1.2	nM	CHEMBL_ACT_18300682
CYP11B1	8.6	IC50	2.5	nM	CHEMBL_ACT_13862704
CYP11B1	8.6	IC50	2.5	nM	CHEMBL_ACT_16422972
CYP11B1	8.6	IC50	2.5	nM	CHEMBL_ACT_25500510
CYP11B1	8.54	IC50	2.9	nM	CHEMBL_ACT_14730293
CYP11B1	8.54	IC50	2.9	nM	CHEMBL_ACT_15030799
CYP11B1	8.54	IC50	2.9	nM	CHEMBL_ACT_15157373
CYP11B1	8.54	IC50	2.9	nM	CHEMBL_ACT_15211553
CYP11B2	8.52	IC50	3	nM	CHEMBL_ACT_15739706
CYP11B1	8.52	IC50	3	nM	CHEMBL_ACT_18078675
CYP11B1	8.22	IC50	6	nM	CHEMBL_ACT_24783444
CYP11B2	8.05	IC50	9	nM	CHEMBL_ACT_13862738
CYP11B1	7.66	IC50	22	nM	CHEMBL_ACT_18300708
P30099	6.96	IC50	111	nM	CHEMBL_ACT_13862710
P15539	6.68	IC50	210	nM	CHEMBL_ACT_15739708
P15393	6.3	IC50	495	nM	CHEMBL_ACT_13862700
CYP19A1	6.07	IC50	856	nM	CHEMBL_ACT_15030781
CYP19A1	5.8	IC50	1585	nM	CHEMBL_ACT_18488044
CYP17A1	5.4	IC50	3981	nM	CHEMBL_ACT_18488036
CYP19A1	5.22	IC50	6000	nM	CHEMBL_ACT_13862732

Target pathways

Aggregated over 2 target gene(s): CYP11B1, CYP11B2.

Top Reactome pathways

15 total, by targets touching each:

Pathway	Targets	Genes
Metabolism	2	CYP11B1, CYP11B2
Disease	2	CYP11B1, CYP11B2
Glucocorticoid biosynthesis	2	CYP11B1, CYP11B2
Metabolism of steroid hormones	2	CYP11B1, CYP11B2
Biological oxidations	2	CYP11B1, CYP11B2
Cytochrome P450 - arranged by substrate type	2	CYP11B1, CYP11B2
Phase I - Functionalization of compounds	2	CYP11B1, CYP11B2
Endogenous sterols	2	CYP11B1, CYP11B2
Metabolism of lipids	2	CYP11B1, CYP11B2
Metabolic disorders of biological oxidation enzymes	2	CYP11B1, CYP11B2
Diseases of metabolism	2	CYP11B1, CYP11B2
Metabolism of steroids	2	CYP11B1, CYP11B2
Mineralocorticoid biosynthesis	1	CYP11B2
Defective CYP11B2 causes CMO-1 deficiency	1	CYP11B2
Defective CYP11B1 causes AH4	1	CYP11B1

Dominant GO biological processes

GO term	Targets
C21-steroid hormone biosynthetic process	2
glucocorticoid biosynthetic process	2
cholesterol metabolic process	2
sterol metabolic process	2
aldosterone biosynthetic process	2
cellular response to hormone stimulus	2
cortisol metabolic process	2
cortisol biosynthetic process	2
cellular response to potassium ion	2
cellular response to peptide hormone stimulus	2
alcohol metabolic process	2
lipid metabolic process	2
steroid biosynthetic process	2
immune response	1
regulation of blood pressure	1

Indications & clinical

Indications

8 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
adrenal gland disorder	4	MONDO:0005495	EFO:0005539
ACTH-dependent Cushing syndrome	3	MONDO:0020528	EFO:1001110
hypertensive disorder	2	MONDO:0005044	EFO:0000537
Cushing syndrome	2	MONDO:0018912	EFO:0003099
hyperaldosteronism	2	MONDO:0003009	HP:0011736
essential hypertension	2	MONDO:0001134	MONDO:0001134
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

Clinical trials

Total trials: 20.

Phase distribution

Phase	Trials
PHASE2	9
PHASE4	4
Not specified	3
PHASE3	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07247058	PHASE4	RECRUITING	Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)
NCT07247162	PHASE4	NOT_YET_RECRUITING	Osilodrostat in Patients With Hypertension Caused by Hypercortisolaemia Due to Cushing’s Syndrome
NCT07268222	PHASE4	RECRUITING	Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS)
NCT07603466	PHASE4	ENROLLING_BY_INVITATION	Combination Osilodrostat and Cabergoline in Cushing’s Disease
NCT02180217	PHASE3	COMPLETED	Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing’s Disease
NCT02697734	PHASE3	COMPLETED	Efficacy and Safety Evaluation of Osilodrostat in Cushing’s Disease
NCT03708900	PHASE2	RECRUITING	Pharmacokinetic (PK), Pharmacodynamic (PD) and Tolerability of Osilodrostat in Pediatric Patients With Cushing’s Syndrome
NCT07104812	PHASE2	RECRUITING	Impact of 1 mg Osilodrostat Therapy on Mild Autonomous Cortisol Secretion (MACS)
NCT00732771	PHASE2	COMPLETED	Proof-of-concept for the Aldosterone Synthase Inhibitor LCI699 in Patients With Primary Hyperaldosteronism
NCT00758524	PHASE2	COMPLETED	A Study to Evaluate Efficacy and Safety of LCI699 in Participants With Essential Hypertension
NCT00817414	PHASE2	COMPLETED	A Study to Evaluate the Effects of LCI699 on Cortisol in Participants With Hypertension
NCT00817635	PHASE2	COMPLETED	A Study to Evaluate the Efficacy and Safety of LCI699 Compared to Placebo in Participants With Resistant Hypertension
NCT01331239	PHASE2	COMPLETED	Safety and Efficacy of LCI699 in Cushing’s Disease Patients
NCT02468193	PHASE2	COMPLETED	Study of Efficacy and Safety of Osilodrostat in Cushing’s Syndrome
NCT03606408	PHASE2	COMPLETED	Roll-over Study in Patients With Endogenous Cushing’s Syndrome for LCI699
NCT02372084	PHASE1	COMPLETED	A Phase 1 Study of Osilodrostat (LCI699) in Healthy Volunteers and Subjects With Impaired Hepatic Function
NCT02399202	PHASE1	COMPLETED	A Phase I Study of Osilodrostat (LCI699) in Healthy Volunteers and Subjects With Impaired Renal Function
NCT05382156	Not specified	ACTIVE_NOT_RECRUITING	Non-interventional Study on Osilodrostat in Patients With Endogenous Cushing’s Syndrome
NCT06430528	Not specified	RECRUITING	A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement
NCT05633953	Not specified	COMPLETED	Osilodrostat for the Treatment of Non-Cushing’s Disease Cushing’s Syndrome

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

13 molecules share ≥1 primary target. Top 13 by shared-target count:

Molecule	Source	Status	Shared targets
ABIRATERONE	ChEMBL + PubChem	Phase 4 (approved)	CYP11B1, CYP11B2
ETOMIDATE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
FLUCONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
KETOCONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
LETROZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
METYRAPONE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
POSACONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP11B2
BAXDROSTAT	ChEMBL	Phase 3	CYP11B1, CYP11B2
DEXFADROSTAT	ChEMBL	Phase 2	CYP11B1, CYP11B2
FADROZOLE	ChEMBL	Phase 2	CYP11B1, CYP11B2
LORUNDROSTAT	ChEMBL	Phase 3	CYP11B2
AZALANSTAT	ChEMBL	Phase 2	CYP11B1
VOROZOLE	ChEMBL	Phase 2	CYP11B1