Biological Activity: NVP-BGT226 is a novel dual PI3K/mTOR inhibitor with an IC50
~1 nM. In cellular assays it could produce nearly complete inhibition
of PI3K signaling at low nanomolar (<50 nM) concentrations. Flow
cytometric analysis revealed an accumulation of cells in the G0–G1 phase
with a concomitant loss in the S-phase. TUNEL assay and the analysis of
Caspase 3/7 and PARP indicated that BGT226 induced cancer cell death
through an apoptosis independent pathway. BGT226 induced autophagy as
indicated by the aggregation and upregulation of the
microtubule-associated protein light chain 3B-II, and p62 degradation.
It is in the phase I/II clinical trials for the treatment of advanced
solid tumors.
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How to Use:
In vitro: BGT226 was used at 0.2 μM concentration in cellular assays to investigate its effects on the PI3K/AKT signaling pathways.
In vivo: BGT226 was dissolved in 90% NMP/10% PEG300 and orally dosed at 5mg/Kg once a day.?
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Reference:
1. Chang KY, et al. Novel phosphoinositide 3-kinase/mTOR dual
inhibitor, NVP-BGT226, displays potent growth-inhibitory activity
against human head and neck cancer cells in vitro and in vivo. (2011)
Clin Cancer Res. 17(22):7116-26.
2. Baumann P, et al. Simultaneous targeting of PI3K and mTOR with
NVP-BGT226 is highly effective in multiple myeloma. (2012) Anticancer
Drugs. 23(1):131-8.
3. Sanchez CG, et al. Preclinical modeling of combined
phosphatidylinositol-3-kinase inhibition with endocrine therapy for
estrogen receptor-positive breast cancer. (2011) Breast Cancer Res.
13(2):R21
4. Fokas E, et al. NVP-BEZ235 and NVP-BGT226, dual
phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors,
enhance tumor and endothelial cell radiosensitivity. (2012) Radiat
Oncol. 7:48
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