Home Cytoskeletal Signaling HSP (HSP90) inhibitor SNX-2112 For research use only.

SNX-2112

Synonyms: PF-04928473

SNX-2112 selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM, uniformly more potent than 17-AAG.

SNX-2112 Chemical Structure

SNX-2112 Chemical Structure

CAS No. 908112-43-6

Purity & Quality Control

SNX-2112 Related Products

Signaling Pathway

HSP (HSP90) Signaling Pathways

HSP (HSP90) Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A375 cells Function assay 24 h Inhibition of Hsp90 in human A375 cells assessed as pS6 degradation after 24 hrs by high content screening, IC50=0.001 μM 19552433
LNCAP cells Proliferation assay 72-144 h Antiproliferative activity against human LNCAP cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.003 μM 19552433
human SW620 cells Proliferation assay 72-144 h Antiproliferative activity against human SW620 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.003 μM 19552433
HT-29 cells Proliferation assay 72-144 h Antiproliferative activity against human HT-29 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.003 μM 19552433
human SK-MEL-5 cells Proliferation assay 72-144 h Antiproliferative activity against human SK-MEL-5 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.006 μM 19552433
sf9 cells Function assay 3 h Binding affinity to human N-terminal polyHis-tagged HSP90beta (D9 to E236) expressed in insect sf9 cells after 3 hrs by fluorescence polarization assay, Ki=0.006 μM 24332488
K562 cells Proliferation assay 72-144 h Antiproliferative activity against human K562 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.006 μM 19552433
MDA-MB-231 cells Proliferation assay 72-144 h Antiproliferative activity against human MDA-MB-231 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.006 μM 19552433
PC3 cells Proliferation assay 72-144 h Antiproliferative activity against human PC3 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.017 μM 19552433
NCI-H460 cells Proliferation assay 72-144 h Antiproliferative activity against human NCI-H460 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.018 μM 19552433
MCF7 cells Function assay Inhibition of HSP90alpha in human MCF7 cells assessed as degradation of Her-2, EC50=0.019 μM 22938030
AU565 cells Function assay 24 h Inhibition of Hsp90 in human AU565 cells assessed as pERK degradation after 24 hrs by high content screening, IC50=0.041 μM 19552433
HCT15 cells Proliferation assay 72-144 h Antiproliferative activity against human HCT15 cells after 72 to 144 hrs by cyquant DNA dye method, IC50=0.052 μM 19552433
MRC5 cells Cytotoxicity assay 48 h Cytotoxicity against human MRC5 cells after 48 hrs by MTT assay, CC50=21.34 μM 22704890
Click to View More Cell Line Experimental Data

Biological Activity

Description SNX-2112 selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM, uniformly more potent than 17-AAG.
Targets
HSP90α [1]
(cell-free assay)		 HSP90β [1]
(cell-free assay)
30 nM(Ka) 30 nM(Ka)
In vitro
In vitro Treatment of BT-474 cells with 1 μM SNX-2112 results in down-regulation of HER2 expression within 3 to 6 hours of drug exposure with near-complete loss of HER2 expression by 10 hours. Treatment with SNX-2112 also results in a decline in total Akt expression. SNX-2112 inhibits cell proliferation with IC50 values ranging from 10 to 50 nM, in BT474, SKBR-3, SKOV-3, MDA-468, MCF-7 and H1650 cancer cells. And these antiproliferative effects are associated with hypophosphorylation of Rb, arrest of G1 and modest levels of apotosis. [1] SNX-2112 competitively binds to the N-terminal adenosine triphosphate binding site of Hsp90. SNX-2112 induces apoptosis via caspase-8, -9, -3, and poly (ADPribose) polymerase cleavage. SNX-2112 inhibits cytokine-inducedAkt and extracellular signal-related kinase (ERK) activation and also overcomes the growth advantages conferred by interleukin-6, insulin-like growth factor-1, and bone marrow stromal cells. SNX-2112 inhibits tube formation by human umbilical vein endothelial cells via abrogation of eNOS/Akt pathway and markedly inhibits osteoclast formation via down-regulation of ERK/c-fos and PU.1. [2] Cell lines (eight cell lines from osteosarcoma, neuroblastoma, hepatoblastoma, and ymphoma) studied demonstrates sensitivity to SNX-2112 with IC50 values ranging from 10-100 nM. A higher dose (70 nM) exhibits a more prolonged inhibition and larger sub-G1 accumulation. Observed levels of Akt1 and C-Raf are markedly reduced over time along with an increase in PARP cleavage. [3] A recent research indicates NX-2112 induces autophagy in a time- and dose-dependent manner via Akt/mTOR/p70S6K inhibition. SNX-2112 induces significant apoptosis and utophagy in human melanoma A-375 cells, and may be an effective targeted therapy agent. [4]
Kinase Assay ATP Displacement Assay
For the protein affinity-displacement assay, a purine-based affinity resin is generated by incubating ATP-linked Sepharose with Jurkat cell lysate (flash frozen and homogenized in saline) at 4 °C. This is then incubated with SNX-2112 for 90 minutes. Proteins eluted by drug are then resolved by SDS-PAGE, visualized with silver staining, and excised from the gel for MS-based identification. Briefly, after destaining and trypsin digestion, peptides are extracted with μC18 ZipTips and then eluted and spotted directly to a conventional stainless steel matrix-assisted laser desorption/ionization target with a saturated solution of α-cyano-4- hydroxycinnamic acid in 50% acetonitrile, 0.15% formic acid. Mass spectra are then acquired using a MALDI-TOF/TOF 4700 Proteomics Analyzer. MS spectra are acquired (1,000 shots per spectrum), and the three peaks from each with the greatest signal-to-noise ratio are automatically submitted for tandem MS analysis (3000 shots per spectrum). The collision energy is 1keV. Air is used as the collision gas. Protein identification is done from the MS and tandem MS data using GPS Explorer software with the integrated Mascot database search engine.
Cell Research Cell lines BT474, SKBR-3, SKOV-3, MDA-468, MCF-7 and H1650 cancer cells
Concentrations 0-500 nM
Incubation Time 24 hours
Method Cell viability is determined by seeding 2-5 × 103 cells per well in 96- well plates and treating with SNX-2112 24 hours after plating in complete medium (200 μL). Each drug concentration is tested in eight wells. Cells are assayed using the Alamar blue viability test after a 96-h incubation. Flow cytometry is done using nuclei stained with ethidium bromide and isolated via the Nusse protocol
In Vivo
In vivo SNX-2112, delivered by its prodrug SNX-5422, inhibits MM cell growth and prolongs survival in a xenograft murine model and blockade of Hsp90 by SNX-2112 not only inhibits MM cell growth but also acts in the bone marrow microenvironment to block angiogenesis and osteoclastogenesis. [2]
Animal Research Animal Models 5 × 106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old).
Dosages 20 or 40 mg/kg
Administration SNX-5422 is administered orally 3 times per week, total 3 weeks.

Chemical Information & Solubility

Molecular Weight 464.48 Formula

C23H27F3N4O3
CAS No. 908112-43-6 SDF Download SNX-2112 SDF
Smiles CC1(CC2=C(C(=O)C1)C(=NN2C3=CC(=C(C=C3)C(=O)N)NC4CCC(CC4)O)C(F)(F)F)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 93 mg/mL ( (200.22 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 1 mg/mL

Water : Insoluble


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In vivo
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Tech Support

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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