Home Cytoskeletal Signaling HSP inhibitor Onalespib (AT13387)

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Onalespib (AT13387) Hsp90 Inhibitor

Cat.No.S1163

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.
Onalespib (AT13387) HSP inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 409.52

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Quality Control

Batch: Purity: 99.94%
99.94

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human HCT116 cells Cytotoxic assay Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.048 μM 20662534
human HCT116 cells Function assay 10 nM 18 h Induction of apoptosis in human HCT116 cells assessed as upregulation of Hsp70 level at 10 nM after 18 hrs by immunoblotting 20662534
human HCT116 cells Function assay 30 nM 18 h Induction of apoptosis in human HCT116 cells assessed as reduction of CDK4 level at 30 nM after 18 hrs by immunoblotting 20662534
human HCT116 cells Function assay 30 nM 18 h Induction of apoptosis in human HCT116 cells assessed as reduction of Raf-1 level at 30 nM after 18 hrs by immunoblotting 20662534
human HCT116 cells Proliferation assay 48 h Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay, IC50=0.08 μM 24763261
human SKBR3 cells Proliferation assay 48 h Antiproliferative activity against human SKBR3 cells after 48 hrs by MTT assay, IC50=0.14 μM 24763261
human MCF7 cells Proliferation assay 48 h Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=0.28 μM 24763261
human A231 cells Proliferation assay 48 h Antiproliferative activity against human A231 cells after 48 hrs by MTT assay, IC50=1.01 μM 24763261
GIST430 Cytotoxicity assay 7 days Cytotoxicity against imatinib-resistant human GIST430 cells assessed as decrease in cell viability after 7 days by alamar blue assay, IC50=0.034μM. 26844689
GIST48 Cytotoxicity assay 7 days Cytotoxicity against imatinib-resistant human GIST48 cells assessed as decrease in cell viability after 7 days by alamar blue assay, IC50=0.055μM. 26844689
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells incubated for 72 hrs by MTT assay, IC50=0.032μM. 29028527
SKBR3 Antiproliferative assay 72 hrs Antiproliferative activity against human SKBR3 cells incubated for 72 hrs by MTT assay, IC50=0.045μM. 29028527
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
NCI-H3122 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB assay, IC50=0.052μM. 29698859
PANC1 Function assay 1 uM 36 hrs Inhibition of HSP90alpha in human PANC1 cells assessed as up-regulation of Hsp70 at 1 uM after 36 hrs by Western blot analysis 30351001
PANC1 Function assay 1 uM 36 hrs Inhibition of HSP90alpha in human PANC1 cells assessed as akt degradation at 1 uM after 36 hrs by Western blot analysis 30351001
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50=0.29μM. 30784881
NCI-H1299 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H1299 cells after 72 hrs by MTT assay, IC50=0.37μM. 30784881
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50=0.44μM. 30784881
Vero E6 Function assay 48 hrs IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h by immunofluorescence-based assay (detecting the viral NP protein in the nucleus of the Vero E6 cells), IC50=0.15488μM. 32353859
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 25 mg/mL (61.04 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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%
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% ddH2O
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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 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.

Chemical Information, Storage & Stability

Molecular Weight 409.52 Formula

C24H31N3O3

 Storage (From the date of receipt)
CAS No. 912999-49-6 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC(C)C1=CC(=C(C=C1O)O)C(=O)N2CC3=C(C2)C=C(C=C3)CN4CCN(CC4)C

Mechanism of Action

Targets/IC50/Ki
HSP90
(Cell-free assay)
18 nM
In vitro
The Kd for Onalespib (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 stoichiometry of binding for this compound is 1.03. Its inhibition of a number of isolated kinases is also investigated, including CDK1, CDK2, CDK4, FGFR3, PKB-b, JAK2, VEGFR2, PDGFRβ and Aurora B. None of the tested kinases are significantly inhibited at concentrations below 30 μM. It is a potent inhibitor of the proliferation 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, it potently inhibits cell proliferation with GI50 values in the range 13–260 nM. The compound also inhibits proliferation of the non-tumorigenic human prostate epithelial cell line PNT2 with a GI50 value of 480 nM.
Kinase Assay
HSP90 competition isothermal calorimetry
Kd values for Onalespib (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 vivo
When given on an intermittent basis, Onalespib (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 this compound observed for mutant EGFR and other biomarkers in vitro and in vivo and the extended retention of it in tumors.
References

Applications

Methods Biomarkers Images PMID
Western blot HSP90 / HSP70 EGFR / p-EGFR / AKT / p-AKT / ERK / p-ERK / S6 / p-S6 AXL / c-Myc / p-Mnk1 / Mnk1 / p-eIF4E / eIF4E
S1163-WB1
28679777
Growth inhibition assay Cell viability
S1163-viability1
28679777

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02898207 Completed
Metastatic High Grade Fallopian Tube Serous Adenocarcinoma|Metastatic Malignant Solid Neoplasm|Metastatic Primary Peritoneal Serous Adenocarcinoma|Metastatic Triple-Negative Breast Carcinoma|Platinum-Resistant Fallopian Tube Carcinoma|Platinum-Resistant Ovarian Carcinoma|Platinum-Resistant Primary Peritoneal Carcinoma|Recurrent Breast Carcinoma|Recurrent High Grade Fallopian Tube Serous Adenocarcinoma|Recurrent High Grade Ovarian Serous Adenocarcinoma|Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma|Recurrent Triple-Negative Breast Carcinoma|Refractory Fallopian Tube Serous Adenocarcinoma|Refractory Ovarian Serous Adenocarcinoma|Refractory Primary Peritoneal Serous Adenocarcinoma|Refractory Triple-Negative Breast Carcinoma|Unresectable High Grade Fallopian Tube Serous Adenocarcinoma|Unresectable Malignant Solid Neoplasm|Unresectable Primary Peritoneal Serous Adenocarcinoma
National Cancer Institute (NCI)
 May 19 2017 Phase 1

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Handling Instructions

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Frequently Asked Questions

Question 1:
How to prepare it for in vivo studies?

Answer:
It 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.

Signaling Pathway Map