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Itraconazole (R 51211)

Name: Itraconazole (R 51211)
Brand: Selleck Chemicals
SKU: S2476
Rating: 5 (30 reviews)

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 30 publications

Purity & Quality Control

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Hedgehog/Smoothened Signaling Pathway Map

Biological Activity

Description

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	NIe2O2ZHfW6ldHnvckBie3OjeR?=			NX\VVm92UW6qaXLpeIlwdiCxZjDDXXA{STRiaX6gbJVu[W5iaHXwZZRw[3m2ZYOgeZNqdmdidHXzeI9{fGW{b37lJIF{KHO3YoP0doF1\SCkeTDIVGxEN02VL13TJI1mfGixZDygTWM2OD1yLkC3JO69VQ>?	NHHIN2gzPDl2OEW2OS=>
human HTLA cells	M1ja[2Z2dmO2aX;uJIF{e2G7		NHfyO2wzOCCvaX7z	Mk\MTY5pcWKrdHnvckBw\iCFWEPDUFEue3SrbYXsZZRm\CCFWEPDVlEhcW5iaIXtZY4hUFSOQTDj[YxteyCycnWtbY5kfWKjdHXkJIZweiB{MDDtbY5{KG2nYYP1doVlKG:wIHThfUA1KGK7IHLleIEh[XK{ZYP0bY4uemWlcoXpeI1mdnRibXXkbYF1\WRibIXjbYZmemG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBKSzVyPUCuNUDPxE1?	MVmyN\|Q{Pzd5Mh?=
LLC-PK1 epithelial cells	NETGV4NHfW6ldHnvckBie3OjeR?=			Mk[0TY5pcWKrdHnvckBw\iCSLXfsfYNweHKxdHXpckwhdW:3c3WgUE1u\HJzYTDlfJBz\XO\|ZXSgbY4hVEyFLWDLNUBmeGm2aHXsbYFtKGOnbHzzJJV{cW6pIHPhcINmcW5vQV2gdI9t[XKrc3H0bY9vKGG\|c3H5MEBKSzVyPUCuNkDPxE1?	MnzUNVI3QTl\|OEm=
human PBMC	MXzDfZRwfG:6aXPpeJkh[XO\|YYm=		NWfxb41QPzJiaB?=	NV;oZW1vS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWEKPQzDhd5Nme3OnZDDhd{Bk\WyuII\pZYJqdGm2eTDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTFwNUOg{txO	NHLxeFQzPDR6NUe4Ny=>
Topp 3 cells	MV;GeY5kfGmxbjDhd5NigQ>?			M37oNGlvcGmkaYTpc44hd2ZiaIXtZY4hS1mSNUGg[ZhxemW\|c3XkJIlvKFSxcICgN{Bk\WyuczDifUBt[W6xc4Tldo9tKGSnbXX0bJlt[XOnIHHzd4F6NCCLQ{WwQVMvPiEQvF2=	NUi0cW5bOTdzOUS3NVY>
human MRC5 cells	Mm\KR5l1d3SxeHnjbZR6KGG\|c3H5			MYjDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNVmM2KGOnbHzzMEBESzVyPUS5MlM{KM7:TR?=	NH;XXFkzODhyNUO5PC=>
human HUVEC cells	NIj4OVRHfW6ldHnvckBie3OjeR?=	NYT6[4VGOiEQvF2=	NIXTc\|AzPCCq	M2fYPGlvcGmkaYTpc44hd2ZiVlXHSnIzKGeueXPvd5lt[XSrb36gbY4hcHWvYX6gTHVXTUNiY3XscJMh[XRiMjD1UUBi\nSncjCyOEBpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{	MWiyNVk{PjVzNB?=

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)

References

+ Expand

Solubility (25°C)

In vitro


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. Click to purchase: PEG300 Tween 80	1.75mg/mL

Chemical Information

Molecular Weight	705.65031
Formula	C₃₅H₃₈Cl₂N₈O₄
CAS No.	84625-61-6
Storage	3 years	-20°C	powder
Storage	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

Download Itraconazole (R 51211) SDF

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.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

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

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