Onalespib (AT13387)

Catalog No.S1163 Batch:S116303

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Technical Data

Formula

C24H31N3O3
Molecular Weight 409.52 CAS No. 912999-49-6
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
HSP90 [1]
(Cell-free assay)
18 nM
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]

Protocol (from reference)

Kinase Assay:[2]
  • HSP90 competition isothermal calorimetry

    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
Cell Assay:[2]
  • Cell lines

    A375, 22RV1 and T474 cells

  • Concentrations

    1 μM

  • Incubation Time

    4 hours

  • Method

    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.
Animal Study:[2]
  • Animal Models

    Athymic BALB /c mice

  • Dosages

    80 mg/kg

  • Administration

    Intraperitoneal adminis tration

Customer Product Validation

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's Onalespib (AT13387) has been cited by 33 publications

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
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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