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XL888

Cat. No. M2070
XL888 Structure
Size Price Availability Quantity
10mg USD 250 In stock
25mg USD 400 In stock
50mg USD 700 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

XL888 is an orally bioavailable, ATP-competitive HSP90 inhibitor with potential antineoplastic activity. XL888 specifically binds to Hsp90, inhibiting its chaperone function and promoting the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. XL888 potently inhibited cell growth, induced apoptosis, and prevented the growth of vemurafenib-resistant melanoma cell lines in vitro and in vivo. XL888 (100 mg/kg) significantly induces the regression or growth inhibition (50%) of established M229R and 1205LuR xenografts in SCID mice. XL888 treatment increased BIM expression, decreased Mcl-1 expression, and induced apoptosis more effectively than dual mitogen-activated protein-extracellular signal-regulated kinase/phosphoinositide 3-kinase (MEK/PI3K) inhibition.

Protocol
Cell Experiment
Cell lines vemurafenib naïve and resistant melanoma cell lines and melanoma cell lines
Preparation method Growth inhibition.
Cells were plated at a density of 2.5 × 104 cells per ml and left to grow overnight before being treated with increasing concentrations of vemurafenib or XL888 as described in (19). Data show the mean of at least three independent experiments ± the S.E. mean.
Concentrations 1nM ~ 10 µM
Incubation time 72 h
Animal Experiment
Animal models BALB SCID mice bearing Xenograft experiments
Formulation 10mM HCl
Dosages 100 mg/kg 3x per week
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 503.64
Formula C29H37N5O3
CAS Number 1149705-71-4
Purity >99%
Solubility DMSO
Storage at -20°C
References

Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90.
Bussenius J, et al. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5396-404. PMID: 22877636.

The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms.
Paraiso KH, et al. Clin Cancer Res. 2012 May 1;18(9):2502-14. PMID: 22351686.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: XL888 supplier, HSP90, inhibitors

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