Itraconazole

別名：R 51211

製品コード：S2476 純度：99.98%

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.

CAS No. 84625-61-6

サイズ	価格(税別)	在庫状況
200mg	JPY 37000	国内在庫あり
1g	JPY 85500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（40）

製品安全説明書

現在のバッチを見る：純度： 99.98%

99.98

Itraconazole関連製品

関連ターゲット	Hedgehog Smoothened GLI	もっと見る
関連製品	Vismodegib (GDC-0449) Cyclopamine GANT61 SAG (Smoothened Agonist) HCl Sonidegib Purmorphamine SANT-1 SAG (Smoothened Agonist) BMS-833923 HPI-4 (Ciliobrevin A) Taladegib (LY2940680) PF-5274857 Glasdegib Jervine Ciliobrevin D MK-4101 JK184	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Stem Cell Signaling Compound Library GPCR Compound Library Stem Cell Differentiation Compound Library	もっと見る

シグナル伝達経路

Hedgehog/Smoothenedシグナル伝達経路

Hedgehog/Smoothened阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
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
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
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
human hepatocytes	Function assay			Inhibition of CYP3A4 in human hepatocytes using testosterone as substrate by HPLC/MS/MS method, IC50=0.07 μM	24948565
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
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
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

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]
実験結果図	Methods	Biomarkers	結果図	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
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT06194864	Not yet recruiting	Drug Interaction	Emalex Biosciences Inc.\|Syneos Health\|Cambridge Cognition Ltd	January 2024	Phase 1
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	January 15 2024	Phase 2
NCT05949385	Not yet recruiting	Pharmacokinetics	Nanjing Zenshine Pharmaceuticals	July 12 2023	Phase 1
NCT05860933	Recruiting	Healthy	Eli Lilly and Company\|Loxo Oncology Inc.	May 8 2023	Phase 1

参考
[1] Isoherranen N, et al. Drug Metab Dispos, 2004, 32(10), 1121-1131. [2] Kim J, et al. Cancer Cell, 2010, 17(4), 388-399. [3] Oakley KL, et al. Antimicrob Agents Chemother, 1997, 41(5), 1124-1126. [4] Zuckerman JM, et al. Infect Control Hosp Epidemiol, 1994, 15(6), 397-410. [5] Leyden J, et al. J Am Acad Dermatol, 1998, 38(5 Pt 3), S42-47. [6] Isoherranen N, et al. Drug Metab Dispos. 2004, 32(10):1121-31. + 展開

参考

+ 展開

化学情報

分子量	705.65031	化学式	C₃₅H₃₈Cl₂N₈O₄
CAS No.	84625-61-6	SDF	Download Itraconazole SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 13 mg/mL ( (18.42 mM)； Warmed with 50℃ water bath; 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

よくある質問（FAQ）

質問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).

回答
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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