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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 |
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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. |
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. |
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in vitro | The Kd for AT13387 binding is 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 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] |
キナーゼアッセイ | HSP90 competition isothermal calorimetry | |
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Kd 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 |
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]
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。
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