Ketoconazole

SKU: orb1310393

Description

Ketoconazole (R-41400) is an imidazole-derived antifungal compound that also acts as a potent CYP3A4 enzyme inhibitor. It is widely used in biochemical research to study drug metabolism, enzyme inhibition, and fungal pathogenesis in both in vitro and in vivo experimental models.

Research Area

Immunology & Inflammation, Infectious Disease & Virology, Metabolism Research, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 65277-42-1
• MW: 531.43
• Purity: >98%
• Formula: C₂₆H₂₈Cl₂N₄O₄
• SMILES: C([C@]1(O[C@@H](COC2=CC=C(C=C2)N3CCN(C(C)=O)CC3)CO1)C4=C(Cl)C=C(Cl)C=C4)N5C=CN=C5
• Target: Cytochrome/MDR
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 20 mg/ml).

Bioactivity

• Target IC50:
  Testosterone 6β-hydroxylase:0.22 mM|Cyclosporine oxidase:0.19 mM
• In Vivo:
  In HT29-S-B6 colorectal cancer cells, Ketoconazole decreased cell proliferation and [3H]thymidine uptake in a dose-dependent manner, with an IC50 of 2.5 mM. Ketoconazole also inhibited [3H]thymidine uptake in both Evsa-T and MDA-MB-231 cell lines, with respective IC50 values of 2 μM and 13 μM. Within 24 hours, Ketoconazole induced a dose-dependent reduction in the S-phase cell population (from 17% to 3%) and a corresponding increase in the Go-G1 phase cell percentage (from 64% to 80%) in HT29-S-B6 cells. By competitively binding with [3H]Dexamethasone, Ketoconazole inhibited fibroblast glucocorticoid receptors, with an IC50 of 0.3 mM. Several Aspergillus species were sensitive to Ketoconazole, with a minimum inhibitory concentration of 0.03 μg/mL.
• In Vitro:
  Intraperitoneal administration of Ketoconazole (25 mg/kg) in rats significantly reduced plasma corticosterone levels and decreased self-administration of low doses of cocaine. Rats treated with Ketoconazole exhibited enhanced bioavailability of digoxin, increasing from 0.68 to 0.84, with the mean absorption time decreasing from 1.1 h to 0.3 h. Moreover, the oral area under the curve (AUC) for digoxin increased from 63 mg·h/L to 411 mg·h/L, while the intravenous AUC also rose from 93 mg·h/L to 486 mg·h/L.
• Cell Research:
  HT29-S-B6 cells (5×105) are plated in 35-mm Petri dishes. The next day, the medium is changed and effectors are added in a small volume (10-20 μL). The incubation medium is renewed every day during the experiments. The same triplicate dishes are used for cell counts, [3H]thymidine incorporation, and flow cytometry. [3H]Thymidine (0.5 μCi) is allowed to incorporate for 24 hours; at the end of incubation, cells are rinsed with 1 mL of medium, detached with 1 mL of trypsin-EDTA, and diluted (1:3) with the culture medium. An aliquot (0.5-1 mL) is used for cell count with a Coulter Counter.(Only for Reference)

Storage & Handling

• Storage: RT
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

12-hydroxylase, 17-hydroxylase, (±)-Ketoconazol, Cyclosporine oxidase, CYP24A1, CYP3A4, CYPs, Cytochrome P450, Extina, Fungal, NADPHoxidase, Ketoconazol, Ketoconazole, Inhibitor, inhibit, Steroid 21-hydroxylase, Ras, Xolegel, R41400, R-41400, R 41400, Testosterone 6 beta-hydroxylase

Compound Identifiers

PubChem CID

456201