Itraconazole (R 51211)

For research use only.

Catalog No.S2476

26 publications

Itraconazole (R 51211) Chemical Structure

CAS No. 84625-61-6

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.

Selleck's Itraconazole (R 51211) has been cited by 26 publications

Purity & Quality Control

Choose Selective Hedgehog/Smoothened Inhibitors

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 MnjZSpVv[3Srb36gZZN{[Xl? NYLiSHpOUW6qaXLpeIlwdiCxZjDDXXA{STRiaX6gbJVu[W5iaHXwZZRw[3m2ZYOgeZNqdmdidHXzeI9{fGW{b37lJIF{KHO3YoP0doF1\SCkeTDIVGxEN02VL13TJI1mfGixZDygTWM2OD1yLkC3JO69VQ>? MlzHNlQ6PDh3NkW=
human HTLA cells MXPGeY5kfGmxbjDhd5NigQ>? MkXuNlAhdWmwcx?= M{K5O2lvcGmkaYTpc44hd2ZiQ2izR2wyNXO2aX31cIF1\WRiQ2izR3IyKGmwIHj1cYFvKEiWTFGgZ4VtdHNicILlMYlv[3WkYYTl[EBnd3JiMkCgcYlveyCvZXHzeZJm\CCxbjDkZZkhPCCkeTDi[ZRiKGG{cnXzeIlvNXKnY4L1bZRu\W62IH3l[IlifGWmIHz1Z4ln\XKjc3WgdoVxd3K2ZYKg[4Vv\SCjc4PhfUwhUUN3ME2wMlEh|ryP M1HDZ|I{PDN5N{ey
LLC-PK1 epithelial cells MYPGeY5kfGmxbjDhd5NigQ>? NITxWJJKdmirYnn0bY9vKG:oIGCt[4x6[2:ycn;0[YlvNCCvb4Xz[UBNNW2mckHhJIV5eHKnc4Pl[EBqdiCOTFOtVGsyKGWyaYTo[Yxq[WxiY3XscJMhfXOrbnegZ4Ft[2Wrbj3BUUBxd2yjcnnzZZRqd25iYYPzZZktKEmFNUC9NE4zKM7:TR?= M4P3SVEzPjl7M{i5
human PBMC NW[xNpR5S3m2b4TvfIlkcXS7IHHzd4F6 MWC3NkBp MkPpR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVGJOSyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVEvPTNizszN M{nlOVI1PDh3N{iz
Topp 3 cells NX;WUmJ[TnWwY4Tpc44h[XO|YYm= Mm[2TY5pcWKrdHnvckBw\iCqdX3hckBEYVB3MTDlfJBz\XO|ZXSgbY4hXG:ycDCzJINmdGy|IHL5JIxidm:|dHXyc4wh\GWvZYTofYxie2ViYYPzZZktKEmFNUC9N{43KM7:TR?= MWOxO|E6PDdzNh?=
human MRC5 cells NXmyXnBHS3m2b4TvfIlkcXS7IHHzd4F6 NFPsPIhEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOWkN3IHPlcIx{NCCFQ{WwQVQ6NjN|IN88US=> MYiyNFgxPTN7OB?=
human HUVEC cells M3HjbmZ2dmO2aX;uJIF{e2G7 M3\GdlIh|ryP MnnQNlQhcA>? MYHJcohq[mm2aX;uJI9nKF[HR1\SNkBodHmlb4P5cIF1cW:wIHnuJIh2dWGwIFjVWmVEKGOnbHzzJIF1KDJidV2gZYZ1\XJiMkSgbJJ{KGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=> NFP1RZIzOTl|NkWxOC=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pACC / ACC / p-S6K / S6K ; 

PubMed: 28103683     


HUVEC were treated with drugs as indicated for 1 h, and AMPK/mTOR activity was monitored by phosphorylation of their respective substrates. Unlike itraconazole, the NPC phenotype-inducing compounds U18666A and imipramine inhibited mTOR without affecting AMPK activity. 

GLI1 / GLI2 / p-AKT1 / AKT1 / Cyclin D1 ; 

PubMed: 27388747     


Pathway components of Hh and AKT signaling are decreased in ASZ001 cells treated with itraconazole. ASZ001 cells were treated with varying concentrations of itraconazole for 24 hours. The levels of GLI1, GLI2, p-AKT1, and cyclin D1 were assessed by Western blotting.

28103683 27388747
Growth inhibition assay
Cell viability; 

PubMed: 24905460     


U87 or C6 cells were treated with indicated concentrations of itraconazole for 36 h. Cell viability was measured by the MTT assay. The data were representative of 5 independent experiments. 

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

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 powder
in solvent
Synonyms N/A
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)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04942652 Not yet recruiting Drug: Itraconazole 200 mg|Drug: Esomeprazole 40 mg Achlorhydria Seoul National University Hospital July 1 2021 Phase 1
NCT04962022 Recruiting Drug: PF-07321332/ritonavir|Drug: Itraconazole Healthy Participant Pfizer July 20 2021 Phase 1
NCT04880980 Recruiting Drug: Terbinafine Pill|Drug: Itraconazole capsule Dermatophyte Infection|Terbinafine Adverse Reaction|Itraconazole Adverse Reaction Pak Emirates Military Hospital March 1 2021 Phase 3

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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

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.

Hedgehog/Smoothened Signaling Pathway Map

Related Hedgehog/Smoothened Products

Tags: buy Itraconazole (R 51211) | Itraconazole (R 51211) supplier | purchase Itraconazole (R 51211) | Itraconazole (R 51211) cost | Itraconazole (R 51211) manufacturer | order Itraconazole (R 51211) | Itraconazole (R 51211) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID