[CAS NO. 908112-43-6]  SNX-2112 (PF-04928473)

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PRODUCTS SPECIFICATIONS [908112-43-6]

Catalog
SLK-S2639
Brand
Selleck
CAS
908112-43-6

DESCRIPTION [908112-43-6]

Overview

MDL-
Molecular Weight464.48
Molecular FormulaC23H27F3N4O3
SMILESO=C(N)C1=CC=C(N2N=C(C(F)(F)F)C3=C2CC(C)(C)CC3=O)C=C1N[C@H]4CC[C@H](O)CC4

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

1 mg5 mg10 mg
1 mM2.1529 mL10.7647 mL21.5295 mL
5 mM0.4306 mL2.1529 mL4.3059 mL
10 mM0.2153 mL1.0765 mL2.1529 mL
50 mM0.0431 mL0.2153 mL0.4306 mL

Description

SNX-2112 (PF-04928473) selectively binds to the ATP pocket of and with 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

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. 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. 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. 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.

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.