Onalespib (AT13387)

製品コードS1163 バッチS116303

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H31N3O3
分子量 409.52 CAS No. 912999-49-6
Solubility (25°C)* 体外 DMSO 25 mg/mL (61.04 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 Onalespib (AT13387) is a selective potent Hsp90 inhibitor with IC50 of 18 nM in A375 cells, displays a long duration of anti-tumor activity. Phase 2.
in vitro Onalespib (AT13387) has a Kd for binding of 0.7 nM. This compares to a Kd of 6.7 nM for the binding of the ansamycin 17-AAG to the same site. The mean stoichiometry of binding for this compound is 1.03. The inhibition of a number of isolated kinases by it is also investigated including CDK 1, CDK 2, CDK4, FGFR3, PKB-b, JAK2, VEGFR2, PDGFRβ and Aurora B. None of the tested kinases are significantly inhibited at concentrations below 30 μM. It is a potent inhibitor of the proliferation and survival of many different cell lines (such as MES-SA cell line) from a variety of different tumor types. Across a panel of 30 tumor cell lines, it potently inhibits cell proliferation with GI50 values in the range 13-260 nM. This compound inhibits proliferation of the non-tumorigenic human prostate epithelial cell line PNT2 with a GI50 value of 480 nM. [2]
in vivo When given on an intermittent basis, Onalespib (AT13387) could be tolerated at doses of up to 70 mg/kg twice weekly or 90 mg/kg once weekly. Body weight loss in mice does not exceed 20% before recovering in all cases except one, and loss is highest following the second dose. Tumor growth inhibition is similar in NCI-H1975 for both dosing regimens. The maintenance of antitumor effects with such a prolonged off-treatment period is consistent with the extended pharmacodynamic action of this compound observed for mutant EGFR and other biomarkers in vitro and in vivo and the extended retention of it in tumors. [2]

プロトコル(参考用のみ)

キナーゼアッセイ HSP90 competition isothermal calorimetry
Kd values for Onalespib (AT13387) binding to HSP90 are determined with a competition Isothermal Calorimetry (ITC) format. ITC experiments are performed on a Micro Cal VP-ITC at 25 °C in a buffer comprising 25 mM Tris, 100 mM NaCl, 1 mM MgCl2 and 1 mM Tris(2-carboxy- ethyl)phosphine at pH 7.4 in order to maintain the higher affinit
細胞アッセイ 細胞株 A375, 22RV1 and T474 cells
濃度 1 μM
反応時間 4 hours
実験の流れ Onalespib (AT13387) is added in 0.1% (v/v) DMSO to human cell lines including A375, 22RV1, T474, DU1 45, LNCa P, MCF-7, DA-MB-468 after they are seeded into 96-well plates. GI50 are determined using a 10-point dose response curve for three cell doubling times. After incubation with this compound, 10% (v/v) Alamar blue is added, and cells are incubated for a further 4 hours. Fluorescence is read.
動物実験 動物モデル Athymic BALB /c mice
投薬量 80 mg/kg
投与方法 Intraperitoneal adminis tration

参考

  • http://mct.aacrjournals.org/cgi/content/meeting_abstract/8/12_MeetingAbstracts/A217
  • https://pubmed.ncbi.nlm.nih.gov/22181674/

カスタマーフィードバック

Data from [Data independently produced by PLoS One, 2013, 8, e59315]

Data from [Data independently produced by , , Cell, 2017, 168(5):856-866]

Data from [Data independently produced by , , PLoS One, 2017, 12(5):e0177878]

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：

In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [11C]HSP990 in Healthy Aging and Neurodegeneration [ J Nucl Med, 2025, jnumed.124.268961] PubMed: 40306968
Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy [ Front Oncol, 2025, 15:1451156] PubMed: 39949745
Radiosynthesis and Evaluation of [18F]FEHSP990 as Novel PET Tracer for Hsp90 PET Imaging [ J Labelled Comp Radiopharm, 2025, 68(4):e4144] PubMed: 40219580
The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer [ Theranostics, 2024, 14(6):2442-2463] PubMed: 38646654
The HSP90 inhibitor HVH-2930 exhibits potent efficacy against trastuzumab-resistant HER2-positive breast cancer [ Theranostics, 2024, 14(6):2442-2463] PubMed: 38646654
ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors [ Nature Communications, 2023, 1221-2023)] PubMed: None
ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors [ Nat Commun, 2023, 14(1):1221] PubMed: 36869047
Enhanced Therapeutic Effects of 177Lu-DOTA-M5A in Combination with Heat Shock Protein 90 Inhibitor Onalespib in Colorectal Cancer Xenografts [ Cancers (Basel), 2023, 15(17)4239] PubMed: 37686514
Enhanced Therapeutic Effects of 177Lu-DOTA-M5A in Combination with Heat Shock Protein 90 Inhibitor Onalespib in Colorectal Cancer Xenografts [ Cancers (Basel), 2023, 15(17)4239] PubMed: 37686514
Combination therapy of tyrosine kinase inhibitor sorafenib with the HSP90 inhibitor onalespib as a novel treatment regimen for thyroid cancer [ Sci Rep, 2023, 10.1038/s41598-023-43486-z] PubMed: 37803074

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。