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Ketoconazole P450 (e.g. CYP17) inhibitor

Name: Ketoconazole
Brand: Selleck Chemicals
SKU: S1353
Availability: InStock
Rating: 5 (25 reviews)

Cat.No.S1353

Ketoconazole inhibits cyclosporine oxidase and testosterone 6 beta-hydroxylase with IC50 of 0.19 mM and 0.22 mM, respectively. This compound is an androgen biosynthesis inhibitor.

Chemical Structure

Molecular Weight: 531.43

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.95%

99.95

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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description
LLC-PK1 epithelial cells	Function assay		Inhibition of P-glycoprotein, human L-MDR1 expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay, IC50=4.8 μM
MCF7 cells	Function assay		Inhibition of CYP26A1 in human MCF7 cells assessed as all-trans retinoic acid metabolism, IC50=12 μM
human THP1 cells	Cytotoxicity assay	48 h	Cytotoxicity against human THP1 cells after 48 hrs, IC50=44 μM
CHO cells	Function assay		Inhibition of CYP24A1 expressed in CHO cells, IC50=0.52 μM
P815B cells	Cytotoxicity assay	24 h	Cytotoxicity against mouse P815B cells after 24 hrs by MTS/PMS assay, LD50=25 μM
V79 11B2 cells	Function assay		Inhibition of human CYP11B2 expressed in V79 11B2 cells, IC50=0.081 μM
V79 cells	Function assay		Inhibition of human CYP24 hydroxylase expressed in V79 cells, IC50=0.312 μM
hamster V79MZh11B1 cells	Function assay		Inhibition of human CYP11B1 expressed in hamster V79MZh11B1 cells, IC50=0.127 μM
hamster V79MZh11B2 cells	Function assay		Inhibition of human CYP11B2 expressed in hamster V79MZh11B2 cells, IC50=0.067 μM
CHO cells	Function assay		Inhibition of human ERG expressed in CHO cells by whole cell patch clamp technique, IC50=1.90546 μM
V79 11B1 cells	Function assay		Inhibition of human CYP11B1 expressed in V79 11B1 cells, IC50=0.224 μM
Topp 3 cells	Function assay		Inhibition of human CYP51 expressed in Topp 3 cells by lanosterol demethylase assay, IC50=0.19 μM
V79 cells	Function assay		Inhibition of human CYP24A1 expressed in chinese hamster V79 cells, IC50=0.312 μM
V79MZ cells	Function assay		Inhibition of human CYP11B2 expressed in hamster V79MZ cells using 11-deoxycorticosterone substrate, IC50=0.067 μM
V79MZh cells	Function assay		Inhibition of human CYP11B2 expressed in hamster V79MZh cells, IC50=0.067 μM
human epidermal keratinocytes	Function assay		Inhibition of CYP24A1 in human epidermal keratinocytes, IC50=0.126 μM
V79MZh cells	Function assay		Inhibition of human CYP11B1 expressed in hamster V79MZh cells, IC50=0.127 μM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	531.43	Formula	C₂₆H₂₈Cl₂N₄O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	65277-42-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	R 41400			Smiles	CC(=O)N1CCN(CC1)C2=CC=C(C=C2)OCC3COC(O3)(CN4C=CN=C4)C5=C(C=C(C=C5)Cl)Cl

Solubility

In vitro
Batch:

Ethanol : 7 mg/mL

DMSO : 3 mg/mL (5.64 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (56.45mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	10%DMSO 1 40%PEG300 2 5%TWEEN80 3 45%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.500mg/ml (6.59mM)	Taking the 1 mL working solution as an example, add 100 μL of 35 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	More active than both Econazole and Miconazole against Malassezia species.
Targets/IC₅₀/Ki	Cyclosporine oxidase ^[1] 0.19 mM Testosterone 6 beta-hydroxylase ^[1] 0.22 mM
In vitro	Ketoconazole interacts with androgen receptors in a competitive fashion in intact human foreskin fibroblasts. This compound competes for [³H]dexamethasone binding to fibroblast glucocorticoid receptors with IC50 of 0.3 mM. ^[2] It reduces cell proliferation and [³H]thymidine incorporation with IC50 of 2.5 mM in the serum independent HT29-S-B6 colon cell clone. This chemical inhibits the incorporation of [³H]thymidine with IC50 of 2 μM and 13 μM in the Evsa-T cell line and MDA-MB-231 cell line, respectively. It induces a decrease of the number of cells in S phase and a corresponding increase of the percentage of cells in Go-G1 in HT29-S-B6 cells. ^[3] It is susceptable to several Malassezia species with minimum inhibitory concentrations (MICs) of 0.03 µg/mL. ^[4]
Kinase Assay	Whole Cell [³H]R1881 Binding Assay
Kinase Assay	Fibroblasts are grown to confluence in five or six 150 cm² tissue culture flasks for routine assay. This usually requires 4-6 weeks from the time of the initial seeding of the cell line. All studies are performed between passages 3-20. Two days before assay, the medium is changed to one lacking fetal calf serum. This is repeated again 24 hours before assay. Competition assays are performed with 0.5-1.0 nM [³H]R1881 and increasing amounts of the nonradioactive compounds. Binding to low affinity sites is determined in the presence of 5 × 10^-7 M R1881 and is subtracted from whole cell binding of [³H]R 1881 obtained in the absence of any inhibitor to assess binding to 5 high affinity site
In vivo	Ketoconazole (25 mg/kg, i.p.) significantly decreases plasma corticosterone and reduces low dose cocaine self-administration without affecting food-reinforced responding in rats. ^[5] This compound raises the AUC of orally administered digoxin from 63 mg x h/L to 411 mg x h/L in rats. It raises the AUC of intravenously administered digoxin from 93 mg × h/L to 486 mg × h/L in rats. This chemical increases digoxin bioavailability from 0.68 to 0.84 in rats, while mean absorption time is reduced from 1.1 hours to 0.3 hour. ^[6]
References	[1] https://pubmed.ncbi.nlm.nih.gov/11309497/ [2] https://pubmed.ncbi.nlm.nih.gov/1526623/ [3] https://pubmed.ncbi.nlm.nih.gov/1458471/ [4] https://pubmed.ncbi.nlm.nih.gov/10792228/ [5] https://pubmed.ncbi.nlm.nih.gov/10933341/ [6] https://pubmed.ncbi.nlm.nih.gov/9654217/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04869449	Recruiting	Glioblastoma\|Glioblastoma Multiforme\|Glioblastoma Multiforme of Brain\|Glioblastoma Multiforme Adult	Milton S. Hershey Medical Center	May 12 2022	Early Phase 1
NCT04212000	Completed	Healthy	Cortendo AB	December 16 2019	Phase 1
NCT03796273	Recruiting	Anatomic Stage IV Breast Cancer AJCC v8\|Astrocytoma\|Breast Carcinoma Metastatic in the Brain\|Glioma\|Invasive Breast Carcinoma\|Oligodendroglioma\|Prognostic Stage IV Breast Cancer AJCC v8\|Recurrent Glioma	Wake Forest University Health Sciences\|National Cancer Institute (NCI)	March 13 2019	Early Phase 1
NCT04872920	Recruiting	Cushing Syndrome	HRA Pharma	December 20 2018	--
NCT03473418	Unknown status	Vaginal Candidiasis	Assiut University	April 1 2018	Phase 3

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