Home Stem Cells & Wnt Hedgehog/Smoothened inhibitor - P450 (e.g. CYP17) inhibitor - Autophagy activator - Fungal inhibitor Itraconazole For research use only.

Itraconazole

Synonyms: R 51211

Itraconazole is a relatively potent inhibitor of CYP3A4 with IC50 of 6.1 nM, used as a triazole antifungal agent. Itraconazole is a potent antagonist of the Hedgehog (Hh) signaling pathway. Itraconazole suppresses the growth of glioblastoma through induction of autophagy.

Itraconazole Chemical Structure

Itraconazole Chemical Structure

CAS No. 84625-61-6

Purity & Quality Control

Itraconazole Related Products

Signaling Pathway

Hedgehog/Smoothened Signaling Pathways

Hedgehog/Smoothened Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human hepatocytes Function assay Inhibition of CYP3A4 in human hepatocytes using testosterone as substrate by HPLC/MS/MS method, IC50=0.07 μM 24948565
human HTLA cells Function assay 20 mins Inhibition of CX3CL1-stimulated CX3CR1 in human HTLA cells pre-incubated for 20 mins measured on day 4 by beta arrestin-recruitment mediated luciferase reporter gene assay, IC50=0.1 μM 23437772
LLC-PK1 epithelial cells Function assay Inhibition of P-glycoprotein, mouse L-mdr1a expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay, IC50=0.2 μM 12699389
human PBMC Cytotoxicity assay 72 h Cytotoxicity against human PBMC assessed as cell viability after 72 hrs by MTT assay, IC50=1.53 μM 24485783
Topp 3 cells Function assay Inhibition of human CYP51 expressed in Topp 3 cells by lanosterol demethylase assay, IC50=3.6 μM 17194716
human MRC5 cells Cytotoxicity assay Cytotoxicity against human MRC5 cells, CC50=49.33 μM 20805398
human HUVEC cells Function assay 2 μM 24 h Inhibition of VEGFR2 glycosylation in human HUVEC cells at 2 uM after 24 hrs by Western blot analysis 21936514
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Biological Activity

Description Itraconazole is a relatively potent inhibitor of CYP3A4 with IC50 of 6.1 nM, used as a triazole antifungal agent. Itraconazole is a potent antagonist of the Hedgehog (Hh) signaling pathway. Itraconazole suppresses the growth of glioblastoma through induction of autophagy.
Targets
CYP3A4 [6]
(human liver microsomes)
6.1 nM
In vitro
In vitro Itraconazole is metabolized into hydroxy-itraconazole (OH-ITZ), a known in vivo metabolite of ITZ, and two new metabolites: keto-itraconazole (keto-ITZ) and N-desalkyl-itraconazole (ND-ITZ). Itraconazole is a substrate for CYP3A in vitro and to characterize the metabolites generated. Itraconazole exhibits an unbound Km of 3.9 nM for CYP3A. Itraconazole metabolites are as potent as or more potent CYP3A4 inhibitors than ITZ itself. [1] Itraconazole appears to act on the essential Hh pathway component Smoothened (SMO) by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation. [2] Itraconazole is active against 60 clinical isolates of Aspergillus spp. with geometric mean (GM) MICs of 0.25 mg/mL. [3] Itraconazole acts primarily by impairing the synthesis of ergosterol, resulting in a defective fungal cell membrane with altered permeability and function. Itraconazole is effective for a wide variety of mycotic infections and some fungal meningeal infections. [4] Itraconazole has an affinity for mammalian cytochrome P-450 enzymes as well as for fungal P-450-dependent enzyme, and thus has the potential for clinically important interactions (e.g., astemizole, terfenadine, rifampin, oral contraceptives, H2 receptor antagonists, warfarin, cyclosporine). [5]
Experimental Result Images Methods Biomarkers Images PMID
Western blot pACC / ACC / p-S6K / S6K GLI1 / GLI2 / p-AKT1 / AKT1 / Cyclin D1 28103683
Growth inhibition assay Cell viability 24905460
In Vivo
In vivo Itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model. [2]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05563766 Not yet recruiting
Esophageal Adenocarcinoma|Esophageal Squamous Cell Carcinoma|Gastroesophageal Junction Carcinoma
VA Office of Research and Development|Durham VA Health Care System|VA Palo Alto Health Care System|Portland VA Medical Center|VA Puget Sound Health Care System|Michael E. DeBakey VA Medical Center|VA Boston Healthcare System
 May 1 2024 Phase 2
NCT06357520 Recruiting
Healthy Participants
AstraZeneca
 April 16 2024 Phase 1
NCT06348888 Recruiting
Advanced Non-small Cell Lung Cancer|EGFR Mutation|HER2 Mutation|Healthy Volunteers
Bayer
 April 10 2024 Phase 1
NCT06362642 Recruiting
Healthy Volunteers
PMV Pharmaceuticals Inc
 March 28 2024 Phase 1

Chemical Information & Solubility

Molecular Weight 705.65031 Formula

C35H38Cl2N8O4
CAS No. 84625-61-6 SDF Download Itraconazole SDF
Smiles CCC(C)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OCC5COC(O5)(CN6C=NC=N6)C7=C(C=C(C=C7)Cl)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 13 mg/mL ( (18.42 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
We are finding the best vehicle to administer Itraconazole to mice. We want a mild vehicle (unlike DMSO) which resembles water, PBS, saline (for i.p/ injection) or methyl cellulose (for oral).

Answer:
We are not able to dissolve S2476 Itraconazole clearly without DMSO. For oral gavage, this compound can be dissolved in 1% CMC Na at 20mg/ml as a homogeneous suspension.

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