Levoketoconazole

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
Levoketoconazole
DrugBank Accession Number
DB05667
Background

Levoketoconazole is a cortisol synthesis inhibitor that is being developed as a therapy for glucose and cholesterol control in patients with type 2 diabetes mellitus.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 531.431
Monoisotopic: 530.148760818
Chemical Formula
C26H28Cl2N4O4
Synonyms
  • Levoketoconazole
External IDs
  • COR-003
  • COR003
  • DIO-902

Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 2.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Not Available

Mechanism of action

Preliminary data suggests that DIO-902 increases insulin sensitivity by lowering cortisol levels. The primary mechanism of action is via inhibition of the 11-β-hydroxylase enzyme, the terminal step in cortisol synthesis in the adrenal gland. DIO-902 has also been shown to lower total and LDL-cholesterol by inhibiting 14-α-demethylase, a key enzyme in cholesterol synthesis. In combination with a typical glucose-lowering agent, such as metformin, DIO-902 may enhance glucose control and improve total and LDL-cholesterol. [DiObex Press Release]

TargetActionsOrganism
UCytochrome P450 11B1, mitochondrialNot AvailableHumans
ULanosterol 14-alpha demethylaseNot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Medicalerrors
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AlfentanilThe metabolism of Alfentanil can be decreased when combined with Levoketoconazole.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Levoketoconazole.
AmbrisentanThe metabolism of Ambrisentan can be decreased when combined with Levoketoconazole.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Levoketoconazole.
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Levoketoconazole.
ApixabanThe metabolism of Apixaban can be decreased when combined with Levoketoconazole.
ApomorphineThe metabolism of Apomorphine can be decreased when combined with Levoketoconazole.
AprepitantThe metabolism of Aprepitant can be decreased when combined with Levoketoconazole.
AripiprazoleThe metabolism of Aripiprazole can be decreased when combined with Levoketoconazole.
Aripiprazole lauroxilThe metabolism of Aripiprazole lauroxil can be decreased when combined with Levoketoconazole.
Interactions
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Food Interactions
Not Available

Products

Products
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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
KetoconazoleShampoo, suspension20 mg/1mLTopicalPreferred Pharmaceuticals, Inc.2012-01-30Not applicableUS flag
KetoconazoleTablet200 mg/1OralBurel Pharmaceuticals, Inc.2020-04-10Not applicableUS flag
KetoconazoleAerosol, foam20 mg/1gTopicalXiromed, Llc2021-05-21Not applicableUS flag
KetoconazoleCream20 mg/1gTopicalEncube Ethicals Private Limited2021-05-27Not applicableUS flag
KetoconazoleCream20 mg/1gTopicalPreferred Pharmaceuticals, Inc.2012-01-30Not applicableUS flag
KetoconazoleCream20 mg/1gTopicalPreferred Pharmaceuticals, Inc.2020-07-01Not applicableUS flag
KetoconazoleCream20 mg/1gTopicalREMEDYREPACK INC.2017-10-06Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
PedizolPAKLevoketoconazole (20 mg/1g) + Miconazole nitrate (20 mg/1mL)TopicalNucare Pharmaceuticals,inc.2002-12-18Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Aminophenyl ethers / Phenoxy compounds / Aniline and substituted anilines / Dialkylarylamines / Dichlorobenzenes / Alkyl aryl ethers / Ketals / Aryl chlorides / N-substituted imidazoles
show 12 more
Substituents
1,3-dichlorobenzene / Acetal / Acetamide / Alkyl aryl ether / Amine / Amino acid or derivatives / Aminophenyl ether / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Aryl chloride
show 34 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
cis-1-acetyl-4-(4-\{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy\}phenyl)piperazine (CHEBI:47518)
Affected organisms
Not Available

Chemical Identifiers

UNII
R9400W927I
CAS number
142128-57-2
InChI Key
XMAYWYJOQHXEEK-ZEQKJWHPSA-N
InChI
InChI=1S/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3/t23-,26-/m1/s1
IUPAC Name
1-[4-(4-{[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one
SMILES
CC(=O)N1CCN(CC1)C1=CC=C(OC[C@@H]2CO[C@](CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1

References

General References
  1. Link [Link]
Human Metabolome Database
HMDB0012242
ChemSpider
43284
BindingDB
31768
ChEBI
47518
ChEMBL
CHEMBL295698
ZINC
ZINC000000643153
PharmGKB
PA450146
PDBe Ligand
KLN
Wikipedia
Levoketoconazole
PDB Entries
2jjp / 2v0m

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentCushing's Disease / Cushing's Syndrome1
3CompletedTreatmentEndogenous Cushing's Syndrome2
2TerminatedTreatmentType 2 Diabetes Mellitus1
2, 3TerminatedTreatmentType 2 Diabetes Mellitus1
1CompletedOtherHealthy Volunteers3
1, 2CompletedTreatmentType 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Aerosol, foamTopical20 mg/1g
CreamTopical20 mg/1g
Shampoo, suspensionTopical20 mg/1mL
TabletOral200 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00931 mg/mLALOGPS
logP4.3ALOGPS
logP4.19ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)6.75ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area69.06 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity138.07 m3·mol-1ChemAxon
Polarizability54.67 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-3530190000-a2b05a2498270bcd4a7e

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
CYP51A1
Uniprot ID
Q16850
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
56805.26 Da

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Fleseriu M, Castinetti F: Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-653. doi: 10.1007/s11102-016-0742-1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Fleseriu M, Castinetti F: Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-653. doi: 10.1007/s11102-016-0742-1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
CYP51A1
Uniprot ID
Q16850
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
56805.26 Da
References
  1. Fleseriu M, Castinetti F: Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-653. doi: 10.1007/s11102-016-0742-1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 17-alpha-monooxygenase activity
Specific Function
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation ...
Gene Name
CYP17A1
Uniprot ID
P05093
Uniprot Name
Steroid 17-alpha-hydroxylase/17,20 lyase
Molecular Weight
57369.995 Da
References
  1. Fleseriu M, Castinetti F: Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-653. doi: 10.1007/s11102-016-0742-1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Specifically catalyzes the 21-hydroxylation of steroids. Required for the adrenal synthesis of mineralocorticoids and glucocorticoids.
Gene Name
CYP21A2
Uniprot ID
P08686
Uniprot Name
Steroid 21-hydroxylase
Molecular Weight
55886.805 Da
References
  1. Fleseriu M, Castinetti F: Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-653. doi: 10.1007/s11102-016-0742-1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
References
  1. Fleseriu M, Castinetti F: Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-653. doi: 10.1007/s11102-016-0742-1. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Inhibition of P-glycoprotein (P-gp_ is assumed based on the P-gp inhibitory activity of racemic levoketoconazole (i.e. ketoconazole).
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. EMA SmPC: Ketoconazole [Link]

Drug created on November 18, 2007 18:26 / Updated on April 16, 2021 04:47