Luminespib (NVP-AUY922)

製品コードS1069 バッチS106906

印刷

化学情報

Chemical Structure Synonyms AUY-922, VER-52296 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H31N3O5
分子量 465.54 CAS No. 747412-49-3
Solubility (25°C)* 体外 DMSO 93 mg/mL warmed with 50ºC water bath (199.76 mM)
Ethanol 93 mg/mL (199.76 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Luminespib (AUY-922, NVP-AUY922, VER-52296) is a highly potent HSP90 inhibitor for HSP90α/β with IC50 of 13 nM /21 nM in cell-free assays, weaker potency against the HSP90 family members GRP94 and TRAP-1, exhibits the tightest binding of any small-molecule HSP90 ligand. Luminespib (AUY-922, NVP-AUY922) effectively downregulates and destabilizes the IGF-1Rβ protein and results in growth inhibition, autophagy and apoptosis. Phase 2.
in vitro NVP-AUY922 inhibits proliferation of various human cancer cell lines in vitro, with an average GI50 of 9 nM. [1] The IC50 values of NVP-AUY922 fall in the range of 2 to 40 nM in these gastric cancer cell lines. IC50 value for the BEAS-2B cells is 28.49 nM. Treatment with NVP-AUY922 does not influence the expression of HSP90, but expression of HSP70 gets elevated by NVP-AUY922 treatment. NVP-AUY922 increases the binding of HSP70 to HSP90. NVP-AUY922 causes p23 dissociation from the HSP90 complex and can then recruit HSP70 to the HSP90 complex. [1] After the treatment with NVP-AUY922, expression of receptor tyrosine kinases including VEGFR1, 2, 3 and PDGFRɑ is decreased. A decrease is also noticed in the expression of Akt and phospho-Akt. Meanwhile, treatment with NVP-AUY922 causes decreased expression of HER-2 in NCI-N87 cells. NVP-AUY922 treatment results in binding of HSP90 to client proteins and setting them up as targets for degradation by the proteasome. NVP-AUY922 can influence cell growth by affecting multiple signaling pathways. In addition, treatment with the proteasome inhibitor, MG132, restores expression of thymidylate synthase, which is decreased by NVP-AUY922. NVP-AUY922 increases the expression of cleaved caspase-3 leading to apoptosis in HSC-2 cells.[1]
in vivo Treatment with NVP-AUY922 causes a robust antitumor response and inhibits p-Akt and VEGF expression in an HSC-2 xenograft model. [2] In BT474, NVP-AUY922 shows complete loss of ERBB2 and substantial depletion of ERα, in addition to reductions in CDK4 and phospho-ERK1/2. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Kinase assay
NVP-AUY922 is dissolved in DMSO at a concentration of 10 mM. NVP-AUY922 is assessed against HSP90α, HSP90β, GRP94, TRAP-1, HSP72, and topoisomerase II. Profiling against a panel of kinases has been carried out and screening against a panel of additional enzymes and receptors is performed at Cerep.
細胞アッセイ 細胞株 Human gastric cancer cells NCI-N87
濃度 1 μM
反応時間 3 days
実験の流れ Human gastric cancer cells NCI-N87 (5-7 ×103 in 50 μL/well) are seeded in 96-well plates and incubated at 37 °C for 24 hours, followed by NVP-AUY922 treatment for 1-3 days at 37 °C. After treatment, the cells are assayed by MTT method and analyzed by microplate reader.
動物実験 動物モデル Female NCr athymic mice bearing WM266.4 human melanoma xenografts
投薬量 50 mg/kg
投与方法 Administered via i.v. or i.p.

カスタマーフィードバック

Data from [J Biol Chem, 2013, 288(23), 16308-20]

, 2011, Dr. Swee Sharp and Professor Paul Workman from Cancer Research UK

Data from [Data independently produced by , , Proc Natl Acad Sci USA, 2014, 111(15): E1528–37 ]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

HSP90 inhibition suppresses tumor glycolytic flux to potentiate the therapeutic efficacy of radiotherapy for head and neck cancer [ Sci Adv, 2024, 10(8):eadk3663] PubMed: 38394204
The pharmacogenomic assessment of molecular epithelial-mesenchymal transition signatures reveals drug susceptibilities in cancer cell lines [ bioRxiv, 2024, 10.1101/2024.01.16.575190] PubMed: none
HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma [ Adv Sci (Weinh), 2023, 10.1002/advs.202302025] PubMed: 37515378
HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma [ Adv Sci (Weinh), 2023, 10(27):e2302025] PubMed: 37515378
HRS mediates tumor immune evasion by regulating proteostasis-associated interferon pathway activation [ Cell Rep, 2023, 10.1016/j.celrep.2023.113352] PubMed: 37948180
Single-cell trajectory analysis reveals a CD9 positive state to contribute to exit from stem cell-like and embryonic diapause states and transit to drug-resistant states [ Cell Death Discov, 2023, 9(1):285] PubMed: 37542044
Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy [ Int J Mol Sci, 2023, 24(18)13830] PubMed: 37762133
Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy [ Int J Mol Sci, 2023, 24(18)13830] PubMed: 37762133
Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL [ Mol Syst Biol, 2022, 18(8):e10855] PubMed: 35959629
NVP-AUY922 alleviates radiation-induced lung injury via inhibition of autophagy-dependent ferroptosis [ Cell Death Discov, 2022, 8(1):86] PubMed: 35220409

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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