AUY922 (NVP-AUY922)
(Synonyms: VER-52296, AUY-922, AUY 922, Luminespib) 目录号 : GC15295
AUY922 (NVP-AUY922)是一种高效且选择性的 HSP90抑制剂，对 HSP90α和 HSP90β的 IC50 值分别为 13nM和 21nM。
Cas No.:747412-49-3
Sample solution is provided at 25 µL, 10mM.
AUY922 (NVP-AUY922) is a potent and selective inhibitor of HSP90[1], effectively inhibiting both HSP90α and HSP90β with similar IC50 values of 13nM and 21nM, respectively[2]. AUY922 (NVP-AUY922) exhibits significant antitumor activity and is commonly utilized in the research of various cancers, including breast cancer, lung cancer[3], and gastrointestinal stromal tumors[4].
AUY922 (NVP-AUY922) inhibited the in vitro proliferation of human tumor cells, which selected for their different tissue origins and molecular features with nanomolar potency (2.3–49.6nmol/L) [5]. AUY922 (NVP-AUY922) (100, 500, 1000nM; 5, 15, 30, 60, 180min) treatment can induce HSP90-p23 dissociation and client protein depletion in a concentration and time dependent manner in BT-474 cells[6].
AUY922 (NVP-AUY922) (50, 75mg/kg) slowed growth of A549 (KRAS-mutant) xenografts and achieved tumor stability and decreased EGF receptor (EGFR) protein expression in H1975 xenografts model mice[7]. AUY922 (NVP-AUY922) (30mg/kg) combined with radiation treatment delayed tumor growth in a supra-additive manner in tumor xenograft model mice[8].
References:
[1]. Schilb A, Riou V, Schoepfer J, et al. Development and implementation of a highly miniaturized confocal 2D-FIDA-based high-throughput screening assay to search for active site modulators of the human heat shock protein 90beta. J Biomol Screen. 2004 Oct;9(7):569-77. doi: 10.1177/1087057104265538. PMID: 15475476.
[2]. Brough PA, Aherne W, Barril X, et al. 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. J Med Chem. 2008 Jan 24;51(2):196-218. doi: 10.1021/jm701018h. Epub 2007 Nov 20. PMID: 18020435.
[3]. Ueno T, Tsukuda K, Toyooka S, et al. Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer. Lung Cancer. 2012 Apr;76(1):26-31. doi: 10.1016/j.lungcan.2011.09.011. Epub 2011 Oct 11. PMID: 21996088.
[4]. Hsueh YS, Yen CC, Shih NY, et al. Autophagy is involved in endogenous and NVP-AUY922-induced KIT degradation in gastrointestinal stromal tumors. Autophagy. 2013 Feb 1;9(2):220-33. doi: 10.4161/auto.22802. Epub 2012 Nov 29. PMID: 23196876; PMCID: PMC3552885.
[5]. Eccles SA, Massey A, Raynaud FI, et al. NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res. 2008 Apr 15;68(8):2850-60. doi: 10.1158/0008-5472.CAN-07-5256. PMID: 18413753.
[6]. Jensen MR, Schoepfer J, Radimerski T, et al. NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Res. 2008;10(2):R33. doi: 10.1186/bcr1996. Epub 2008 Apr 22. PMID: 18430202; PMCID: PMC2397535.
[7]. Garon EB, Finn RS, Hamidi H, et al. The HSP90 inhibitor NVP-AUY922 potently inhibits non-small cell lung cancer growth. Mol Cancer Ther. 2013 Jun;12(6):890-900. doi: 10.1158/1535-7163.MCT-12-0998. Epub 2013 Mar 14. PMID: 23493311; PMCID: PMC3681857.
[8]. Gandhi N, Wild AT, Chettiar ST, et al. Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells. Cancer Biol Ther. 2013 Apr;14(4):347-56. doi: 10.4161/cbt.23626. Epub 2013 Jan 28. PMID: 23358469; PMCID: PMC3667875.
AUY922 (NVP-AUY922)是一种高效且选择性的HSP90抑制剂[1]，对HSP90α和HSP90β的IC50值分别为13nM和21nM[2]。AUY922 (NVP-AUY922)具有显著的抗肿瘤活性，常用于乳腺癌、肺癌[3]和胃肠道间质瘤[4]等多种癌症的研究。
AUY922 (NVP-AUY922)可以以纳摩尔级效力（2.3–49.6nmol/L）抑制不同组织来源和分子特征的人类肿瘤细胞的体外增殖[5]。在BT-474细胞中，AUY922 (NVP-AUY922)（100, 500, 1000nM；5, 15, 30, 60, 180分钟）处理可以以浓度和时间依赖性的方式诱导HSP90-p23解离和相关蛋白降解[6]。
AUY922 (NVP-AUY922)（50, 75mg/kg）处理可以减缓A549（KRAS 突变）异种移植瘤在小鼠体内的生长，并可以在H1975异种移植瘤小鼠中实现了肿瘤稳定并降低EGF受体蛋白表达[7]。AUY922 (NVP-AUY922)（30mg/kg）与放射治疗联合使用，可以显著延迟肿瘤移植模型小鼠中的肿瘤生长[8]。
| Cell experiment [1]: | |
Cell lines | BT-474 cells |
Preparation Method | BT-474 cells were treated with AUY922 (NVP-AUY922) for different time. Then total cell extracts were prepared and the expression of HSP90 were analyzed by Western blot analysis. The amount of p23 associated with HSP90 was determined by immunoprecipitating p23 followed by immunoblotting for HSP90. |
Reaction Conditions | 100, 500, 1000nM; 5, 15, 30, 60, 180min |
Applications | AUY922 (NVP-AUY922) induces HSP90-p23 dissociation and client protein depletion in a concentration- and time dependent manner. |
| Animal experiment [2]: | |
Animal models | Non–Small Cell Lung cancer xenograft mouse model |
Preparation Method | Mice carrying subcutaneous A549 xenograft tumors were treated with 25 to 75 mg/kg AUY922 (NVP-AUY922). Then the tumor volume were measured manually with calipers at the indicated time. |
Dosage form | 25, 50, 75mg/kg; weekly,5 weeks; i.v. |
Applications | AUY922 (NVP-AUY922) treatment can reduce tumor growth rates in xenograft models in a dose-dependent manner. |
References: | |
| Cas No. | 747412-49-3 | SDF | |
| 别名 | VER-52296, AUY-922, AUY 922, Luminespib | ||
| 化学名 | (5Z)-N-ethyl-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-[4-(morpholin-4-ylmethyl)phenyl]-2H-1,2-oxazole-3-carboxamide | ||
| Canonical SMILES | CCNC(=O)C1=C(C(=C2C=C(C(=CC2=O)O)C(C)C)ON1)C3=CC=C(C=C3)CN4CCOCC4 | ||
| 分子式 | C26H31N3O5 | 分子量 | 465.5 |
| 溶解度 | ≥ 23.3 mg/mL in DMSO, ≥ 100.6 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| 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 | 2.1482 mL | 10.7411 mL | 21.4823 mL |
| 5 mM | 0.4296 mL | 2.1482 mL | 4.2965 mL |
| 10 mM | 0.2148 mL | 1.0741 mL | 2.1482 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
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- Purity: >98.00%
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