SNX2112

SKU: orb1300885

Description

SNX2112 (PF-04928473) is a potent, orally bioavailable small molecule inhibitor of Hsp90, exhibiting a dissociation constant (Kd) of 16 nM. It is utilized in cancer research to study oncogenic client protein degradation and has demonstrated antitumor activity in both cellular assays and animal xenograft models.

Research Area

Cell Biology, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 908112-43-6
• MW: 464.48
• Purity: 99.95%
• Formula: C₂₃H₂₇F₃N₄O₃
• SMILES: CC1(C)Cc2c(c(nn2-c2ccc(C(N)=O)c(NC3CCC(O)CC3)c2)C(F)(F)F)C(=O)C1
• Target: HSP,Autophagy
• Solubility: Ethanol:1 mg/mL (2.15 mM);DMSO:86 mg/mL (185.15 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.1 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  TRAP1:862 nM|HSP90 α:30 nM(Ka)|HSP90 β:30 nM(Ka)|GRP94:4275 nM
• 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.
• 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.
• Cell Research:
  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)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

HSP90α, HSP90β, SNX 2112, SNX2112, SNX-2112, PF04928473, PF-04928473, PF 04928473

Compound Identifiers

PubChem CID

24772860