Itraconazole
(Synonyms: 伊曲康唑 ; R51211) 目录号 : GC11056
An antifungal agent and hedgehog pathway inhibitor
Cas No.:84625-61-6
Sample solution is provided at 25 µL, 10mM.
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Itraconazole is a potent inhibitor of CYP3A4 which can be used as a triazole antifungal agent [1].
Cytochrome P450 3A4, abbreviated CYP3A4, is an important enzymethat oxidizessmall foreign organic molecules (xenobiotics).
In vitro: Itraconazole was 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 was a substrate for CYP3A and to characterize the metabolites generated. Itraconazole exhibited 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 was pharmacologically distinct from other azole antifungal agents. Itraconazole has been shown to inhibit both the hedgehog signaling pathway and angiogenesis [2] Itraconazole was active against 60 clinical isolates of Aspergillus spp. with geometric mean (GM) MICs of 0.25 mg/mL [3]. Itraconazoleshowed 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 [4].
In vivo: Oral Administration of itraconazole (200 mg) once daily for 4 days increased the area under the midazolam concentration-time curve from 10 to 15 times (p < 0.001) and mean peak concentrations three to four times (p < 0.001) compared with the placebo phase [5].
References:
[1]. Isoherranen N1,Kunze KL,Allen KE,Nelson WL,Thummel KE. Role of itraconazole metabolites in CYP3A4 inhibition.Drug Metab Dispos.2004 Oct;32(10):1121-31. Epub 2004 Jul 8.
[2]. Kim J1,Tang JY,Gong R,Kim J,Lee JJ,Clemons KV,Chong CR, et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth.Cancer Cell.2010 Apr 13;17(4):388-99. doi: 10.1016/j.ccr.2010.02.027.
[3]. Oakley KL1,Moore CB,Denning DW. In vitro activity of SCH-56592 and comparison with activities of amphotericin B and itraconazole against Aspergillus spp.Antimicrob Agents Chemother.1997 May;41(5):1124-6.
[4]. Leyden J1. Pharmacokinetics and pharmacology of terbinafine and itraconazole.J Am Acad Dermatol.1998 May;38(5 Pt 3):S42-7.
[5]. Olkkola, K.T., J.T. Backman, and P.J. Neuvonen, Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clinical Pharmacology & Therapeutics, 1994. 55(5): p. 481-485.
| Cell experiment [1]: | |
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Cell lines |
C. glabrata, C. kefyr |
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Preparation method |
The solubility of this compound in DMSO is > 8.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.016 μg/ml |
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Applications |
Itraconazole showed antifungal activity against 206 isolates of C. glabrata. For 144 isolates, two or more replicate test results were recovered from the database. In five replicate tests with two bioassay strains of C. kefyr (SA and ATCC 46764), the IC50 of itraconazole was 0.016 mg/L. |
| Animal experiment [2]: | |
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Animal models |
CD1 mice model of disseminated candidiasis |
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Dosage form |
5 mg/kg, twice daily for 5 days |
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Application |
Treatment with ITZ led to lower numbers of CFU per gram of kidney. The survival rates for mice inoculated with strain Sr and isolate B were 7 of 10 in mice treated with ITZ. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Odds F C, Bossche H V. Antifungal activity of itraconazole compared with hydroxy-itraconazole in vitro[J]. Journal of Antimicrobial Chemotherapy, 2000, 45(3): 371-373. [2]. Valentin A, Le Guennec R, Rodriguez E, et al. Comparative resistance of Candida albicans clinical isolates to fluconazole and itraconazole in vitro and in vivo in a murine model[J]. Antimicrobial agents and chemotherapy, 1996, 40(6): 1342-1345. | |
| Cas No. | 84625-61-6 | SDF | |
| 别名 | 伊曲康唑 ; R51211 | ||
| 化学名 | 2-butan-2-yl-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one | ||
| Canonical 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 | ||
| 分子式 | C35H38Cl2N8O4 | 分子量 | 705.63 |
| 溶解度 | ≥ 8.83mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4172 mL | 7.0859 mL | 14.1717 mL |
| 5 mM | 0.2834 mL | 1.4172 mL | 2.8343 mL |
| 10 mM | 0.1417 mL | 0.7086 mL | 1.4172 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet