SNX-2112 (PF-04928473)

Catalog No.S2639

SNX-2112 (PF-04928473) Chemical Structure

Molecular Weight(MW): 464.48

SNX-2112 (PF-04928473) selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM, uniformly more potent than 17-AAG.

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In DMSO USD 500 In stock
USD 270 In stock
USD 370 In stock
USD 970 In stock
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Biological Activity

Description SNX-2112 (PF-04928473) selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM, uniformly more potent than 17-AAG.
HSP90α [1]
(cell-free assay)
HSP90β [1]
(cell-free assay)
30 nM(Ka) 30 nM(Ka)
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A375 cells MVTGeY5kfGmxbjDhd5NigQ>? M{\Zb|I1KGh? NY[wcJZzUW6qaXLpeIlwdiCxZjDId5A6OCCrbjDoeY1idiCDM{e1JINmdGy|IHHzd4V{e2WmIHHzJJBUPiCmZXfyZYRifGmxbjDh[pRmeiB{NDDodpMh[nliaHnnbEBkd262ZX70JJNkemWnbnnu[{whUUN3ME2wMlAxOSEQvF2= MXqxPVU2OjR|Mx?=
LNCAP cells NG\4OJpRem:uaX\ldoF1cW:wIHHzd4F6 NYnXUnRUPzJvMUS0JIg> NFjrV4tCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFzOR2FRKGOnbHzzJIFnfGW{IEeyJJRwKDF2NDDodpMh[nliY4nxeYFvfCCGTlGg[JlmKG2ndHjv[EwhUUN3ME2wMlAxOyEQvF2= NHy1dokyQTV3MkSzNy=>
human SW620 cells NFrNbHhRem:uaX\ldoF1cW:wIHHzd4F6 MWq3Nk0yPDRiaB?= NWjwRlQ2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTW|YzOCClZXzsd{Bi\nSncjC3NkB1dyBzNESgbJJ{KGK7IHP5dZVidnRiRF7BJIR6\SCvZYToc4QtKEmFNUC9NE4xODNizszN NV\B[o9COTl3NUK0N|M>
HT-29 cells MXLQdo9tcW[ncnH0bY9vKGG|c3H5 NHH3dok4Oi1zNESgbC=> NFj4OJlCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjUMVI6KGOnbHzzJIFnfGW{IEeyJJRwKDF2NDDodpMh[nliY4nxeYFvfCCGTlGg[JlmKG2ndHjv[EwhUUN3ME2wMlAxOyEQvF2= MlzUNVk2PTJ2M{O=
human SK-MEL-5 cells NYDYRnR5WHKxbHnm[ZJifGmxbjDhd5NigQ>? MmnxO|IuOTR2IHi= MUnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFONLV3FUE02KGOnbHzzJIFnfGW{IEeyJJRwKDF2NDDodpMh[nliY4nxeYFvfCCGTlGg[JlmKG2ndHjv[EwhUUN3ME2wMlAxPiEQvF2= NWTwRoNuOTl3NUK0N|M>
sf9 cells MYPGeY5kfGmxbjDhd5NigQ>? MoHVN{Bp NFSyb3JDcW6maX7nJIFn\mmwaYT5JJRwKGi3bXHuJG4ufGW{bXnuZYwheG:ueVjpd{11[WepZXSgTHNRQTCkZYThJEhFQSC2bzDFNlM3MSCneIDy[ZN{\WRiaX6gbY5{\WO2IIPmPUBk\WyuczDh[pRmeiB|IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5MEBMcT1yLkCwOkDPxE1? MkDzNlQ{OzJ2OEi=
K562 cells NGGwWXBRem:uaX\ldoF1cW:wIHHzd4F6 NX2wT2ZDPzJvMUS0JIg> NIfOem5CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFu1OlIh[2WubIOgZYZ1\XJiN{KgeI8hOTR2IHjyd{BjgSCleYH1ZY51KESQQTDkfYUhdWW2aH;kMEBKSzVyPUCuNFA3KM7:TR?= MknDNVk2PTJ2M{O=
MDA-MB-231 cells M2PBcnBzd2yrZnXyZZRqd25iYYPzZZk> M2LtS|czNTF2NDDo NWHTeYszSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNSGEuVUJvMkOxJINmdGy|IHHmeIVzKDd{IITvJFE1PCCqcoOgZpkh[3mzdXHueEBFVkFiZInlJI1mfGixZDygTWM2OD1yLkCwOkDPxE1? NF;PSWkyQTV3MkSzNy=>
PC3 cells M{DFbnBzd2yrZnXyZZRqd25iYYPzZZk> MlrEO|IuOTR2IHi= Mn:2RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCSQ{OgZ4VtdHNiYX\0[ZIhPzJidH:gNVQ1KGi{czDifUBkgXG3YX70JGRPSSCmeXWgcYV1cG:mLDDJR|UxRTBwMEG3JO69VQ>? NV[xd2FJOTl3NUK0N|M>
NCI-H460 cells NGfmd4xRem:uaX\ldoF1cW:wIHHzd4F6 NHS4SZY4Oi1zNESgbC=> M17tTmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg1PjBiY3XscJMh[W[2ZYKgO|IhfG9iMUS0JIhzeyCkeTDjfZF2[W62IFTORUBlgWVibXX0bI9lNCCLQ{WwQVAvODF6IN88US=> Mn;ZNVk2PTJ2M{O=
MCF7 cells MkXPSpVv[3Srb36gZZN{[Xl? NGT6fJJKdmirYnn0bY9vKG:oIFjTVFkx[WyyaHGgbY4hcHWvYX6gUWNHPyClZXzsd{Bie3Onc4Pl[EBieyCmZXfyZYRifGmxbjDv[kBJ\XJvMjygSWM2OD1yLkCxPUDPxE1? M2\HVVIzQTN6MEOw
AU565 cells NVrneXBUTnWwY4Tpc44h[XO|YYm= MYGyOEBp MkP1TY5pcWKrdHnvckBw\iCKc4C5NEBqdiCqdX3hckBCXTV4NTDj[YxteyCjc4Pld5Nm\CCjczDwSXJMKGSnZ4Lh[IF1cW:wIHHmeIVzKDJ2IHjyd{BjgSCqaXfoJINwdnSnboSgd4Nz\WWwaX7nMEBKSzVyPUCuNFQyKM7:TR?= NVX6SnBiOTl3NUK0N|M>
HCT15 cells M1zRNHBzd2yrZnXyZZRqd25iYYPzZZk> NFW5N4o4Oi1zNESgbC=> NUO4NppOSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR3QyPSClZXzsd{Bi\nSncjC3NkB1dyBzNESgbJJ{KGK7IHP5dZVidnRiRF7BJIR6\SCvZYToc4QtKEmFNUC9NE4xPTJizszN NIHONFAyQTV3MkSzNy=>

... Click to View More Cell Line Experimental Data

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]


Kinase Assay:[1]
+ Expand

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:[1]
+ Expand
  • 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
    (Only for Reference)
Animal Research:[2]
+ Expand
  • Animal Models: 5 × 106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old).
  • Formulation: SNX-5422 is dissolved in 1% carboxy methylcellulose/0.5% Tween 80 at 10 mg/mL and stored at 4 °C for in vivo stud
  • Dosages: 20 or 40 mg/kg
  • Administration: SNX-5422 is administered orally 3 times per week, total 3 weeks.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 93 mg/mL (200.22 mM)
Ethanol 1 mg/mL (2.15 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order:
0.5% CMC+0.25% Tween 80
For best results, use promptly after mixing.
30 mg/mL

* 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.

Chemical Information

Molecular Weight 464.48


CAS No. 908112-43-6
Storage powder
in solvent
Synonyms N/A

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID