BGT226 maleate

SKU: orb1689309

Description

BGT226 maleate

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1245537-68-1
• MW: 650.6
• Purity: 98.77%
• Formula: C₂₈H₂₅F₃N₆O₂·C₄H₄O₄
• SMILES: OC(=O)\C=C/C(O)=O.COc1ccc(cn1)-c1ccc2ncc3n(C)c(=O)n(-c4ccc(N5CCNCC5)c(c4)C(F)(F)F)c3c2c1
• Target: Autophagy,PI3K,mTOR,Apoptosis
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:60 mg/mL (92.22 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.07 mM)

Bioactivity

• Target IC50:
  PI3Kγ:38 nM|PI3Kβ:63 nM|PI3Kα:4 nM
• In Vivo:
  In a xenografted animal model, NVP-BGT226 significantly delays tumor growth in a dose-dependent manner, along with suppressed cytoplasmic expression of p-p70 S6 kinase an the presence of autophagosome formation. NVP-BGT226 inhibits tumor growth in a dose-dependent manner in a FaDu cell xenografted mouse model. Oral administration of NVP-BGT226 at 2.5 and 5 mg/kg for 3 weeks causes 34.7% and 76.1% reduction o the tumor growth on day 21, respectively (compared with control). NVP-BGT226 displays comparable Inhibition against tumor growth to rapamycin the final volume of both groups is significantly smaller than those treated with LY294002 (a PI3K inhibitor) o the control.
• In Vitro:
  The anti Proliferative and pro-apoptotic effects of NVP-BGT226 are independent of bcr-abl status the activation o the AKT/mTOR signal cascade is suppressed by NVP-BGT226 in a concentration and time-dependent manner. Flow cytometric analysis exhibits an accumulation of cells in the G(0)-G(1) phase with concomitant loss in the S-phase. NVP-BGT226 displays potent growth inhibitory activity against All tested cell lines including SCC4, TU183 and KB cell lines wit the IC50 ranging from 7.4 to 30.1 nM. Notably, both Detroit 562 and HONE-1 cells, which express PIK3CA mutation H1047R, are still sensitive to the growth inhibitory effect of NVP-BGT226 treatment. In addition the sensitivity to NVP-BGT226 between HONE-1 cells and its cisplatin-resistant variant is almost identical. Results o the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay an the analysis of caspase 3/7 and PARP indicates that NVP-BGT226 induces cancer cell death through an apoptosis-independent pathway. NVP-BGT226 induces autophagy as indicated b the aggregation and upregulation o the microtubule-associated protein light chain 3B-II, and p62 degradation. Gene silencing of Beclin1 or cotreatment o the autophagosome inhibitor, 3-methyladenine, inhibit the NVP-BGT226-induced autophagy and leads to the retrieval of colony survival NVP-BGT226 inhibits growth in common myeloma cell lines and Primary myeloma cells (such as NCI-H929, U266, RPMI-8226 and OPM2 mM cell lines) at nanomolar concentration in a time-dependent and dose-dependent manner. NVP-BGT226 inhibits phosphorylation of protein kinase B (Akt), P70S6k and 4E-BP-1 in a time-dependent and dose-dependent manner.
• Cell Research:
  NCI-H929, U266, RPMI-8226 and OPM2 mM cells are seeded in 96-well plates at a concentration of 1.5 × 10^4 cells/well in RPMI medium supplemented with 10% fetal bovine serum with or without NVP-BGT226 that is to be tested. After 36 hours, BrdU-labelling solution is added final concentration 10 μM), and cells are cultured for a Other 12 hours in a humidified atmosphere (37℃/5% CO2). Then the plates are centrifuged (10 min, 300 g), an the supernatants are discarded the plates are dried at 60 °C for 2 hours. After fixation with ethanol/HCl for 30 min at -20 °C the DNA is partially digested by nuclease treatment for 30 min at 37℃he cells are washed three times with medium and incubated with anti-BrdU-POD labelling solution for 30 min at 37℃he anti-POD solution is removed an the cells are washed three times with washing buffer the ABTS substratee solution is added, and absorbance is measured in a microplate reader at 405 nM with a reference wave length of 490 nM.(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.
• Disclaimer: For research use only

Alternative Names

PI3Kγ, PI3Kβ, PI3K, PI3Kα, Phosphoinositide 3-kinase, BGT 226, BGT 226 Maleate, BGT226, BGT-226, BGT226 Maleate, BGT226 maleate, BGT-226 maleate, BGT-226 Maleate, Autophagy, Apoptosis, NVP-BGT 226, NVP-BGT226, NVP-BGT-226, NVP-BGT226 (maleate), inhibit, mTOR, Mammalian target of Rapamycin, Inhibitor

Compound Identifiers

PubChem CID

57336745