Home Stem Cells & Wnt Hedgehog/Smoothened inhibitor - P450 (e.g. CYP17) inhibitor - Autophagy activator - Fungal inhibitor Itraconazole (R 51211)

Itraconazole (R 51211)

Catalog No.S2476

For research use only.

Itraconazole (R 51211) 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 (R 51211) Chemical Structure

CAS No. 84625-61-6

Selleck's Itraconazole (R 51211) has been cited by 27 publications

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Biological Activity

Description Itraconazole (R 51211) 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

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human hepatocytes M4nldGZ2dmO2aX;uJIF{e2G7 NV3xblVEUW6qaXLpeIlwdiCxZjDDXXA{STRiaX6gbJVu[W5iaHXwZZRw[3m2ZYOgeZNqdmdidHXzeI9{fGW{b37lJIF{KHO3YoP0doF1\SCkeTDIVGxEN02VL13TJI1mfGixZDygTWM2OD1yLkC3JO69VQ>? M4\Sc|I1QTR6NU[1
human HTLA cells M{fIXmZ2dmO2aX;uJIF{e2G7 MXGyNEBucW6| NFnXd4FKdmirYnn0bY9vKG:oIFPYN2NNOS2|dHnteYxifGWmIFPYN2NTOSCrbjDoeY1idiCKVFzBJINmdGy|IIDy[U1qdmO3YnH0[YQh\m:{IEKwJI1qdnNibXXhd5Vz\WRib36g[IF6KDRiYomgZoV1[SCjcoLld5Rqdi2{ZXPyeYl1dWWwdDDt[YRq[XSnZDDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEmFNUC9NE4yKM7:TR?= M4PIeVI{PDN5N{ey
LLC-PK1 epithelial cells M{jYOWZ2dmO2aX;uJIF{e2G7 MWPJcohq[mm2aX;uJI9nKFBvZ3z5Z49xem:2ZXnuMEBud3W|ZTDMMY1lejGjIHX4dJJme3OnZDDpckBNVENvUFuxJIVxcXSqZXzpZYwh[2WubIOgeZNqdmdiY3HsZ4Vqdi2DTTDwc4xiemm|YYTpc44h[XO|YYmsJGlEPTB;MD6yJO69VQ>? NHrKeGwyOjZ7OUO4PS=>
human PBMC NX3WcJFDS3m2b4TvfIlkcXS7IHHzd4F6 MkO0O|IhcA>? NHvONHBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBRSk2FIHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:OS53MzFOwG0> M4THd|I1PDh3N{iz
Topp 3 cells NVfzTIZUTnWwY4Tpc44h[XO|YYm= M2iyNWlvcGmkaYTpc44hd2ZiaIXtZY4hS1mSNUGg[ZhxemW|c3XkJIlvKFSxcICgN{Bk\WyuczDifUBt[W6xc4Tldo9tKGSnbXX0bJlt[XOnIHHzd4F6NCCLQ{WwQVMvPiEQvF2= M3zzWVE4OTl2N{G2
human MRC5 cells M3vBbGN6fG:2b4jpZ4l1gSCjc4PhfS=> MW\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNVmM2KGOnbHzzMEBESzVyPUS5MlM{KM7:TR?= NUm3OIY3OjB6MEWzPVg>
human HUVEC cells M1LMUmZ2dmO2aX;uJIF{e2G7 M2rWN|Ih|ryP NF3jW2YzPCCq NFG5XJFKdmirYnn0bY9vKG:oIG\FS2ZTOiCpbInjc5N6dGG2aX;uJIlvKGi3bXHuJGhWXkWFIHPlcIx{KGG2IEKgeW0h[W[2ZYKgNlQhcHK|IHL5JHdme3Sncn6gZoxwfCCjbnHsfZNqew>? NX\YeFhGOjF7M{[1NVQ>
Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot pACC / ACC / p-S6K / S6K ; GLI1 / GLI2 / p-AKT1 / AKT1 / Cyclin D1 28103683 27388747
Growth inhibition assay Cell viability 24905460
In vivo Itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model. [2]

Protocol (from reference)

Solubility (25°C)

In vitro

 DMSO 7 mg/mL warmed
(9.91 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMSO+40% PEG 300+10% Tween 80+45% ddH2O
For best results, use promptly after mixing.

 1.75mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 705.65031
Formula

C35H38Cl2N8O4
CAS No. 84625-61-6
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

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

mg/kg g μL

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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05156892 Not yet recruiting Drug: SUBA-itraconazole|Drug: Tamoxifen Ovarian Cancer Anthony Joshua FRACP|Royal Prince Alfred Hospital Sydney Australia|Concord Hospital|Prince of Wales Hospital Sydney|St Vincent''s Hospital Sydney February 1 2022 Phase 1
NCT05154136 Completed Drug: Etrumadenant|Drug: Itraconazole Healthy Participants Arcus Biosciences Inc. October 27 2021 Phase 1
NCT04942652 Completed Drug: Itraconazole 200 mg|Drug: Esomeprazole 40 mg Achlorhydria Seoul National University Hospital July 13 2021 Phase 1
NCT04962022 Completed Drug: PF-07321332/ritonavir|Drug: Itraconazole Healthy Participant Pfizer July 20 2021 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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