Ganetespib (STA-9090)

Description

Biological Activity

Protocol(Only for Reference)

Clinical Trial Information( data from http://clinicaltrials.gov)

Chemical Information

Cell Assay: ^[1]

Animal Study: ^[4]

References

Name: Ganetespib (STA-9090)
Brand: Selleckchem
SKU: S1159

貨號 Cat. No.: S1159
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Ganetespib (STA-9090)

Catalog No.S1159

Ganetespib is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474.

Size

Price

Stock

Quantity

10mM/1mLIn DMSO	USD 380	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 466	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 1348	In stock	0 1 2 3 4 5 6 7 8 9 10
200mg	USD 3112	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Cell lines	OSA cells
Concentrations	0.001-1μM
Incubation Time	5 days
Method	A total of 1.5 × 10³ OSA cells are seeded in 96-well plates in 10% serum-containing complete medium and incubated overnight to determine the 50% inhibitory concentrations. Plates are, harvested at day 5 following 0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 μM Ganetespib, treatment and analyzed. Fluorescence measurements are made using a plate reader with excitation at 485 nm and emission detection at 530 nm. Relative cell number is calculated as a percentage of the control wells: absorbance of sample/absorbance of DMSO treated cells × 100.

Animal Models	Female severe combined immune-deficient (SCID) mice
Dosages	25 mg/kg/day for 3 days
Administration	Tail vein injection
Solubility	1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01562015	Recruiting	Non Small Cell Lung Cancer	Synta Pharmaceuticals Corp.	2012-04	Phase 2
NCT01579994	Recruiting	Advanced Lung Cancer	Memorial Sloan-Kettering Cancer Center	2012-04	Phase 1\|Phase 2
NCT01677455	Recruiting	Breast Cancer\|HER-2 Positive Breast Cancer\|Triple Negative Breast Cancer	Synta Pharmaceuticals Corp.	2012-07	Phase 2
NCT01590160	Not yet recruiting	Lung Cancer - Malignant Pleural Mesothelioma	University College, London\|Cancer Research UK	2012-09	Phase 1\|Phase 2
NCT01798485	Recruiting	Non-Small-Cell Lung Adenocarcinoma\|Non-small Cell Lung Cancer Stage IIIB\|Non-small Cell Lung Cancer Stage IV\|Non-small Cell Lung Cancer Metastatic	Synta Pharmaceuticals Corp.	2013-03	Phase 3

Description

Ganetespib is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474.

In vitro

The 50% inhibitory concentrations (IC50) for Ganetespib against malignant mast cell lines are 10-50 times lower than that for 17-AAG, indicating that triazolone class of HSP90 inhibitors likely exhibits greater potency than geldanamycin based inhibitors. ^[1] Ganetespib inhibits MG63 cell lines with IC50 of 43 nM. ^[1] Ganetespib binds to the ATP-binding domain at the N-terminus of Hsp90 and serves as a potent Hsp90 inhibitor by causing degradation of multiple oncogenic Hsp90 client proteins including HER2/neu, mutated EGFR, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2 and c-Met as well as Wilms’tumor 1. ^[2] Ganetespib, at low nanomolar concentrations, potently arrests cell proliferation and induces apoptosis in a wide variety of human cancer cell lines, including many receptor tyrosine kinase inhibitor- and tanespimycin-resistant cell lines. Ganetespib exhibits potent cytotoxicity in a range of solid and hematologic tumor cell lines, including those that express mutated kinases that confer resistance to small-molecule tyrosine kinase inhibitors. ^[3] Ganetespib treatment rapidly caused the degradation of known Hsp90 client proteins, exhibits superior potency to the ansamycin inhibitor 17-AAG, and shows sustained activity even with short exposure times.^[3] In anohter study, Ganetespib induces apoptosis of malignant canine mast cell lines. Ganetespib is active at significantly lower concentrations for C2 and BR canine malignant mast cells with IC50 of 19 and 4 nM, respectively, while 17-AAG inhibits C2 and BR canine malignant mast cells with IC50 of 958 and 44 nM, respectively. ^[4] Both the expression of WT and mutant Kit are downregulated by 100 nM Ganetespib after 24 hours in all lines treated including C2 and BMCMCs cells. However, no effects on PI3K or HSP90 expression are observed following treatment with Ganetespib.^[4]

Administration of Ganetespib leads to significant tumor shrinkage in several tumor xenograft models in mice and appears to be less toxic. Furthermore Ganetespib demonstrated better tumor penetration compared with tanespimycin.^[2] Ganetespib inhibits in vivo tumor growth in both malignant mast cell and OSA xenograft models. Ganetespib significantly inhibits tumor growth when dosed with two repeating cycles of 25 mg/kg/day for 3 days, with a %T/C value of 18. Ganetespib is well-tolerated, with the vehicle and Ganetespib groups having average bodyweight changes relative to the start of the study of +0.3% and -8.1% on day 17, respectively.^[4]

Download Ganetespib (STA-9090) SDF

Molecular Weight (MW)	364.4
Formula	C₂₀H₂₀N₄O₃
CAS No.	888216-25-9

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	40 mg/mL (109 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	9 mg/mL (24 mM)
	In vivo	1% DMSO/30% polyethylene glycol/1% Tween 80,	30 mg/mL
* <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.