Comparison

Onalespib (AT13387) European Partner

Item no. S1163-5000
Manufacturer Selleckchem
CASRN 912999-49-6
Amount 5 g
Quantity options 10 mg 1 g 10 g 10 mM/1 mL 200 mg 5 mg 50 mg 5 g
Category
Type Inhibitors
Specific against other
Smiles CC(C)C1=CC(=C(C=C1O)O)C(=O)N2CC3=C(C2)C=C(C=C3)CN4CCN(CC4)C
ECLASS 10.1 32160490
ECLASS 11.0 32160490
UNSPSC 12000000
Alias Hsp90,HSP (e.g. HSP90)
Similar products AT13387
Available
Storage Conditions
2 years -80 in solvent
Molecular Weight
409, 52
Administration
Intraperitoneal adminis tration
Animal Models
Athymic BALB /c mice
Cell lines
A375, 22RV1 and T474 cells
Concentrations
1 uM
Dosages
80 mg/kg
Formulation
17.5% cyclodextrin
IC50
18 nM [1], 18 nM [1], 18 nM [1], 18 nM [1], 18 nM [1], 18 nM [1]
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, PDGFRbeta and Aurora B. None of the tested kinases are significantly inhibited at concentrations below 30 uM. 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]
Incubation Time
4 hours
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 affinity.
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.
Solubility (25C)
DMSO 25 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information
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.
Chemical Name
(2, 4-dihydroxy-5-isopropylphenyl)(5-((4-methylpiperazin-1-yl)methyl)isoindolin-2-yl)methanone

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Amount: 5 g
Available: In stock
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