Onalespib (AT13387)

製品コードS1163 バッチS116303

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C ₂₄H₃₁N₃O₃
	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
* <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	The K_d for AT13387 binding is 0.7 nM. This compares to a K_d of 6.7 nM for the binding of the ansamycin 17-AAG to the same site. The mean stoichio metry of binding for AT13387 is 1.03. The inhibition of a number of isolated kinases by AT13387 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. AT13387 is a potent inhibitor of the proliferat ion 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, AT13387 potently inhibits cell proliferation with GI50 values in the range 13-260 nM. AT13387 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, 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 AT13387 observed for mutant EGFR and other biomarkers in vitro and in vivo and the extended retention of AT13387 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
キナーゼアッセイ	K_d values for 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	The human cell lines including A375, 22RV1, T474, DU1 45, LNCa P, MCF-7, DA-MB-468 are seeded into 96-well plates before the addition of AT13387 in 0.1% (v/v) DMSO. GI50 are determined using a 10-point dose response curve for three cell doubling times. After AT13387 incubation 10% (v/v), Alamar blueis 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

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：

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
Combination therapy of tyrosine kinase inhibitor sorafenib with the HSP90 inhibitor onalespib as a novel treatment regimen for thyroid cancer [ Sci Rep, 2023, 13(1):16844]	PubMed: 37803074
Radiosynthesis and preclinical evaluation of [11C]SNX-ab as an Hsp90α,β isoform-selective PET probe for in vivo brain and tumour imaging [ EJNMMI Radiopharm Chem, 2023, 8(1):2]	PubMed: 36715827
In Vitro Characterization of 177Lu-DOTA-M5A Anti-Carcinoembryonic Antigen Humanized Antibody and HSP90 Inhibition for Potentiated Radioimmunotherapy of Colorectal Cancer [ Front Oncol, 2022, 12:849338]	PubMed: 35433442
HSP90 Inhibitors Modulate SARS-CoV-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation and Barrier Dysfunction [ Front Physiol, 2022, 13:812199]	PubMed: 35388292
deepOrganoid: A brightfield cell viability model for screening matrix-embedded organoids [ SLAS Discov, 2022, 27(3):175-184]	PubMed: 35314378

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。