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CAS No. 912999-49-6
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.
Selleck's Onalespib (AT13387) has been cited by 18 publications
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Relative effect of pharmacological HSP90 inhibition by (B) onalespib (AT13387, 10-40 nM) on the viability of FANCA wild-type and FANCA null cells under normal conditions or with increasing concentrations of MMC. Left panels indicate the effects of the indicated inhibitor on cell growth; middle panels the effects onMMCtolerance in FANCA-wild-type cells; right panels the effects onMMCtolerance in FANCA null cells Data presented as the mean ± SEM from 2 independent experiments.
Cell, 2017, 168(5):856-866. Onalespib (AT13387) purchased from Selleck.
IC50 determinations of compound S1 and S13 on heat shock poteins ATPase activity using ADP fluorescence assay. (A) inhibition of HSP70 (B) inhibition of HSP90 The test compounds were diluted from mother plates (10 mM in 100% (v/v) DMSO) into series of concentration (in 2.0% (v/v) DMSO). AT13387 and 17-DMAG were used as positive controls in each assay. Data were performed in triplicate and analyzed by GraphPad.Prism.
PLoS One 2013 8, e59315. Onalespib (AT13387) purchased from Selleck.
The cultured cells were pretreated with the indicated doses of onalespib for 60 min, and then stimulated by 10 μM of PGF2α or vehicle for 10 min. The cell extracts were then subjected to SDS-PAGE with subsequent Western blot analysis with antibodies against phospho-specific p38 MAP kinase or p38 MAP kinase. The histogram shows the quantitative representations of the levels of phosphorylated p38 MAP kinase after normalization with respect to p38 MAP kinase obtained from laser densitometric analysis. The levels were expressed as the fold increase to the basal levels presented as lane 1. Each value represents the mean ± S.E.M. of triplicate determinations from three independent cell preparations. *p<0.05 compared to the value of control. **p<0.05 compared to the value of PGF2α alone.
PLoS One, 2017, 12(5):e0177878. Onalespib (AT13387) purchased from Selleck.
Purity & Quality Control
Choose Selective HSP (HSP90) Inhibitors
|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.|
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. 
|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. |
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
|In vitro||DMSO||25 mg/mL (61.04 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+ddH2O (prepare before use)
For best results, use promptly after mixing.
* 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.
In vivo Formulation Calculator (Clear solution)
|Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)|
|Dosage||mg/kg||Average weight of animals||g||Dosing volume per animal||ul||Number of animals|
|Step 2: Enter the in vivo formulation ()|
|% DMSO % % Tween 80 % ddH2O|
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take μL DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
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Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01712217||Completed||Drug: AT13387|Drug: Crizotinib||Non-small Cell Lung Cancer(NSCLC)||Astex Pharmaceuticals Inc.||October 2012||Phase 1|Phase 2|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
How to prepare the compound for in vivo studies?
S1163 AT13387 can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution. But after stayed for about 1 hour, the precipitation will goes out. So it is recommended to be prepared before use.