Levoketoconazole

Summary

Levoketoconazole (CHEMBL295698) is an approved small molecule (ATC H02CA04) targeting CYP11B1 and CYP17A1; indicated across 5 conditions including cushing syndrome and adrenal gland hyperfunction.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: H02CA04
• Targets: 2 (CYP11B1, CYP17A1)
• Indications: 5 conditions
• Clinical trials: 152
• Chemistry: 531.4 Da · C26H28Cl2N4O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL295698
Name	Levoketoconazole
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	47576
ChEBI	CHEBI:47518
ATC	H02CA04
Molecular formula	C26H28Cl2N4O4
Molecular weight	531.4
InChIKey	XMAYWYJOQHXEEK-ZEQKJWHPSA-N

SMILES: CC(=O)N1CCN(CC1)C2=CC=C(C=C2)OC[C@@H]3CO[C@@](O3)(CN4C=CN=C4)C5=C(C=C(C=C5)Cl)Cl

IUPAC name: 1-[4-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone

ChEBI definition: A cis-1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine which dioxolane moiety has (2S,4R)-configuration.

Also known as: (-)-(2s,4r)-ketoconazole, 2s,4r ketoconazole, 2s,4r-ketoconazole, COR-003, COR003, DIO-902, Ketoconazole, (2s,4r)-, Levoketoconazol, Levoketoconazole, Normocort, Recorlev, LEVOKETOCONAZOLE

Patent coverage: 2,426 distinct patent families (6,603 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 6,563 (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	6.22	0.1%	P15538
CYP17A1	CYP17A1	Inhibition	7.42	0.1%	P05093

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Cytochrome P450 3A4.

Bioactivity

ChEMBL activities: 2 potent at pChembl ≥ 5 of 2 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP3A4	7.57	IC50	26.9	nM	CHEMBL_ACT_23259675
CYP3A4	7.1	IC50	79	nM	CHEMBL_ACT_29186736

Target pathways

Aggregated over 2 target gene(s): CYP11B1, CYP17A1.

Top Reactome pathways

15 total, by targets touching each:

Pathway	Targets	Genes
Glucocorticoid biosynthesis	2	CYP11B1, CYP17A1
Metabolism	1	CYP11B1
Disease	1	CYP11B1
Androgen biosynthesis	1	CYP17A1
Metabolism of steroid hormones	1	CYP11B1
Biological oxidations	1	CYP11B1
Cytochrome P450 - arranged by substrate type	1	CYP11B1
Phase I - Functionalization of compounds	1	CYP11B1
Endogenous sterols	1	CYP11B1
Metabolism of lipids	1	CYP11B1
Defective CYP11B1 causes AH4	1	CYP11B1
Defective CYP17A1 causes AH5	1	CYP17A1
Metabolic disorders of biological oxidation enzymes	1	CYP11B1
Diseases of metabolism	1	CYP11B1
Metabolism of steroids	1	CYP11B1

Dominant GO biological processes

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

Indications & clinical

Indications

5 indications (3 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
Cushing syndrome	4	MONDO:0018912	EFO:0003099
adrenal gland hyperfunction	4	MONDO:0006640	EFO:1000797
adrenal gland disorder	4	MONDO:0005495	EFO:0005539
ACTH-dependent Cushing syndrome	3	MONDO:0020528	EFO:1001110
type 2 diabetes mellitus	2	MONDO:0005148	MONDO:0005148

Clinical trials

Total trials: 152.

Phase distribution

Phase	Trials
PHASE1	85
PHASE2	26
PHASE3	14
Not specified	8
PHASE4	7
EARLY_PHASE1	6
PHASE1/PHASE2	4
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07333170	PHASE4	NOT_YET_RECRUITING	Comparison of the Efficacy of Topical Luliconazole 2% Cream vs Topical Ketoconazole 1% Cream in the Treatment of Pityriasis Versicolor.
NCT07471178	PHASE4	NOT_YET_RECRUITING	Mycological Efficacy and Safety of Ketoconazole 2% Shampoo With a Seven-Day Versus Three-Day Treatment Duration in Pityriasis Versicolor
NCT00703846	PHASE4	COMPLETED	STUDY TO ASSESS THE LONG-TERM SAFETY OF EXTINA (KETOCONAZOLE) FOAM, 2%
NCT00824863	PHASE4	COMPLETED	Safety and Efficacy of Ketoconazole 2% Foam in the Treatment of Pityrosporum Folliculitis
NCT00830388	PHASE4	COMPLETED	Ketoconazole Foam 2% for the Treatment of Versicolor
NCT01288521	PHASE4	COMPLETED	Pharmacogenetics to Predict Drug Interactions in Kidney Transplant Recipients
NCT01378520	PHASE4	COMPLETED	Effect of Ketoconazole on Breathlessness
NCT00000579	PHASE3	COMPLETED	Acute Respiratory Distress Syndrome Clinical Network (ARDSNet)
NCT00002760	PHASE3	COMPLETED	Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer
NCT00002855	PHASE3	COMPLETED	Chemotherapy Plus Hormone Therapy Versus Androgen Suppression in Treating Patients With Metastatic or Unresectable Prostate Cancer
NCT00024167	PHASE3	TERMINATED	Chemotherapy With or Without Strontium-89 in Treating Patients With Prostate Cancer
NCT00027859	PHASE3	COMPLETED	Hormone Therapy Compared With Combination Chemotherapy in Treating Patients With Prostate Cancer
NCT00030654	PHASE3	COMPLETED	Hormone Therapy Plus Chemotherapy in Treating Patients With Prostate Cancer
NCT00622089	PHASE2/PHASE3	TERMINATED	Open Label Safety & Pharmacodynamic Study 24Wk w/DIO-902 Combo w/Metformin & Atorvastatin in T2DM Patients
NCT00675714	PHASE2/PHASE3	TERMINATED	Assessment of the Treatment of Severely Burned With Anabolic Agents on Clinical Outcomes, Recovery and Rehabilitation
NCT01110330	PHASE3	TERMINATED	An Efficacy Study of a New Formulation of Ketoconazole 2% Cream in Patients With Tinea Pedis, Commonly Known as Athlete’s Foot
NCT01838551	PHASE3	COMPLETED	Treatment for Endogenous Cushing’s Syndrome
NCT02606383	PHASE3	WITHDRAWN	Non-inferiority Phase III Trial Comparing Dapaconazole Cream 2% With Ketoconazole Cream 2% in Patients With Tinea Pedis
NCT03277690	PHASE3	COMPLETED	A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing’s Syndrome.
NCT03320486	PHASE3	COMPLETED	Non-inferiority Trial of Dapaconazole Versus Ketoconazole
NCT03473418	PHASE3	UNKNOWN	Ketoconazole Gel Versus Terconazole Cream for Vaginal Candidiasis
NCT03621280	PHASE3	COMPLETED	Open-label Treatment in Cushing’s Syndrome
NCT03845348	PHASE3	UNKNOWN	To Evaluate the Efficacy and Safety of Shampoo TD03 and TD07 in Scalp Diseases
NCT00859781	PHASE2	ACTIVE_NOT_RECRUITING	177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients With Prostate Cancer
NCT00003084	PHASE2	COMPLETED	Combination Chemotherapy With Ketoconazole in Treating Patients With Prostate Cancer
NCT00006371	PHASE2	TERMINATED	A Phase II Trial of Early Medical Adrenalectomy for D0.5 Prostate Cancer
NCT00014352	PHASE2	COMPLETED	Combination Chemotherapy Plus Warfarin in Treating Patients With Prostate Cancer
NCT00019695	PHASE2	TERMINATED	Ketoconazole With or Without Alendronate Sodium in Treating Patients With Metastatic Prostate Cancer
NCT00211393	PHASE2	COMPLETED	A Pilot Study of the Treatment of Central Serous Chorioretinopathy With Ketoconazole
NCT00212095	PHASE2	COMPLETED	Docetaxel Combined With Ketoconazole in Treatment of Breast Cancer
NCT00298155	PHASE2	COMPLETED	Maximal Suppression of the Androgen Axis in Clinically Localized Prostate Cancer
NCT00309894	PHASE2	COMPLETED	Ketoconazole, Hydrocortisone, and GM-CSF in Treating Patients With Progressive Prostate Cancer After Hormone Therapy
NCT00393848	PHASE2	COMPLETED	Effectiveness of Two Types of Treatment in Restoring Muscle After Hip or Knee Surgery
NCT00403559	PHASE2	COMPLETED	A 4 Week Study of Elidel (Pimecrolimus) for the Treatment of Seborrheic Dermatitis
NCT00447473	PHASE2	TERMINATED	Trial of GM-CSF Given in Combination With Ketoconazole and Mitoxantrone in Patients With Progressive Prostate Cancer
NCT00460031	PHASE2	COMPLETED	Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy
NCT00494663	PHASE2	TERMINATED	A Phase 2b Study of DIO-902 or DIO-902 Placebo in Addition to Metformin and Atorvastatin or Atorvastatin Placebo for Type 2 Diabetes
NCT00536991	PHASE1/PHASE2	TERMINATED	Calcitriol in Combination With Ketoconazole and Therapeutic Hydrocortisone in Treating Patients With Prostate Cancer
NCT00586898	PHASE2	COMPLETED	Rapid Hormonal Cycling as Treatment for Patients With Prostate Cancer: The Men’s Cycle
NCT00697437	PHASE2	COMPLETED	Effect of Ketoconazole Inhibition of CYP3A on Urinary Excretion of Docetaxel

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 14 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

26 molecules share ≥1 primary target. Top 26 by shared-target count:

Molecule	Source	Status	Shared targets
ABIRATERONE	ChEMBL + PubChem	Phase 4 (approved)	CYP11B1, CYP17A1
FLUCONAZOLE	ChEMBL + PubChem	Phase 4 (approved)	CYP11B1, CYP17A1
LETROZOLE	ChEMBL + PubChem	Phase 4 (approved)	CYP11B1, CYP17A1
METYRAPONE	ChEMBL + PubChem	Phase 4 (approved)	CYP11B1, CYP17A1
OSILODROSTAT	ChEMBL + PubChem	Phase 4 (approved)	CYP11B1, CYP17A1
KETOCONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP17A1
POSACONAZOLE	ChEMBL	Phase 4 (approved)	CYP11B1, CYP17A1
AZALANSTAT	ChEMBL	Phase 2	CYP11B1, CYP17A1
CLOTRIMAZOLE	ChEMBL + PubChem	Phase 4 (approved)	CYP17A1
ECONAZOLE	ChEMBL + PubChem	Phase 4 (approved)	CYP17A1
MICONAZOLE	ChEMBL + PubChem	Phase 4 (approved)	CYP17A1
AMINOGLUTETHIMIDE	ChEMBL	Phase 4 (approved)	CYP17A1
BIFONAZOLE	ChEMBL	Phase 4 (approved)	CYP17A1
ETOMIDATE	ChEMBL	Phase 4 (approved)	CYP11B1
ISOCONAZOLE	ChEMBL	Phase 4 (approved)	CYP17A1
TESTOSTERONE PROPIONATE	ChEMBL	Phase 4 (approved)	CYP17A1
TIOCONAZOLE	ChEMBL	Phase 4 (approved)	CYP17A1
BAXDROSTAT	ChEMBL	Phase 3	CYP11B1
GALETERONE	ChEMBL	Phase 3	CYP17A1
ORTERONEL	ChEMBL	Phase 3	CYP17A1
DEXFADROSTAT	ChEMBL	Phase 2	CYP11B1
FADROZOLE	ChEMBL	Phase 2	CYP11B1
VOROZOLE	ChEMBL	Phase 2	CYP11B1
Bicalutamide	PubChem	Approved	CYP17A1
Enzalutamide	PubChem	Approved	CYP17A1
Flutamide	PubChem	Approved	CYP17A1