Alvespimycin hydrochloride

SKU: orb1300892

Description

Alvespimycin hydrochloride

Research Area

Cell Biology, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 467214-21-7
• MW: 653.21
• Purity: 99.94%
• Formula: C₃₂H₄₈N₄O₈·HCl
• SMILES: Cl.COC1CC(C)CC2=C(NCCN(C)C)C(=O)C=C(NC(=O)C(C)=CC=CC(OC)C(OC(N)=O)C(C)=CC(C)C1O)C2=O
• Target: Apoptosis,HSP
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.06 mM);Ethanol:6.5 mg/mL (9.95 mM);DMSO:19.6 mg/mL (30.01 mM)

Bioactivity

• Target IC50:
  HSP90:62 nM|GRP94:65 nM (EC50)
• In Vivo:
  Alvespimycin treatment at 5 mg/kg or 25 mg/kg thrice per week significantly reduces tumor growth of TMK-1 xenografts, by significantly reducing vessel area and numbers of proliferating tumor cells in sections. Consistent the inhibition of FAK signaling in vivo, Alvespimycin treatment at 25 mg/kg three times a week significantly suppresses tumor growth, and metastasis of ME180 and SiHa xenografts in mice. Administration of Alvespimycin at 10 mg/kg for 16 days significantly decreases the white blood cell count and prolongs the survival in a TCL1-SCID transplant mouse model.
• In Vitro:
  Alvespimycin displays ~2 times potency against human Hsp90 than 17-AAG, with IC50 of 62 nM versus 119 nM. In SKBR3 and SKOV3 cells which over-express Hsp90 client protein Her2, Alvespimycin causes down-regulation of Her2 with EC50 of 8 nM and 46 nM, respectively, as well as induction of Hsp70 with EC50 of 4 nM and 14 nM, respectively, leading to significant cytotoxicity with GI50 of 29 nM and 32 nM, respectively, consistent with Hsp90 inhibition. Alvespimycin in combination with vorinostat synergistically induces apoptosis of the cultured MCL cells as well as primary MCL cells, more potently than either agent alone, by markedly attenuating the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and Akt. In contrast to 17-AAG which is only active for IKKβ in chronic lymphocytic leukemia (CLL) cells, Alvespimycin treatment effectively leads to depletion of the Hsp90 client protein, resulting in diminished NF-κB p50/p65 DNA binding, decreased NF-κB target gene transcription, and caspase-dependent apoptosis. By targeting the NF-κB family, Alvespimycin selectively mediates dose- and time-dependent cytotoxicity against CLL cells, but not normal T cells or NK cells important for immune surveillance.
• Cell Research:
  Cells are exposed to various concentrations of 17-DMAG for 24, or 48 hours. For the assessment of cytotoxicity, MTT reagent is then added, and plates are incubated for an additional 24 hours before spectrophotometric measurement. Apoptosis is determined by staining with annexin V-fluorescein isothiocyanate and propidium iodide (PI).(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

HSP, HSP90, Heat shock proteins, Inhibitor, KOS 1022, KOS1022, KOS-1022, inhibit, NSC707545, NSC-707545, NSC 707545, Alvespimycin, Alvespimycin (17-DMAG) HCl, Alvespimycin hydrochloride, Alvespimycin Hydrochloride, 17-DMAG, 17-DMAG Hydrochloride, 17-DMAG hydrochloride, BMS 826476, BMS826476, BMS-826476, Apoptosis

Compound Identifiers

PubChem CID

73989685