BGT226 (NVP-BGT226) maleate

Catalog No.S2749

For research use only.

BGT226 (NVP-BGT226) maleate is a novel class I PI3K/mTOR inhibitor for PI3Kα/β/γ with IC50 of 4 nM/63 nM/38 nM. Phase 1/2.

BGT226 (NVP-BGT226) maleate Chemical Structure

CAS No. 1245537-68-1

Selleck's BGT226 (NVP-BGT226) maleate has been cited by 8 Publications

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Biological Activity

Description BGT226 (NVP-BGT226) maleate is a novel class I PI3K/mTOR inhibitor for PI3Kα/β/γ with IC50 of 4 nM/63 nM/38 nM. Phase 1/2.
Targets
mTOR [1] PI3Kα [1]
(filter-binding assay)
PI3Kγ [1]
(filter-binding assay)
PI3Kβ [1]
(filter-binding assay)
4 nM 38 nM 63 nM
In vitro

The anti-proliferative and pro-apoptotic effects of NVP-BGT226 are independent of bcr-abl status. The activation of 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 with 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 of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and 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 by the aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and p62 degradation. Gene silencing of Beclin1 or cotreatment of the autophagosome inhibitor, 3-methyladenine, inhibits the NVP-BGT226-induced autophagy and leads to the retrieval of colony survival.[2] 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 concentrations 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. The stimulatory effect of insulin-like growth factor 1, interleukin-6 and conditioned medium of HS-5 stromal cells on myeloma cell growth is completely abrogated by NVP-BGT226. Inhibition of phosphoinositol-3-kinase/mammalian target of rapamycin by NVP-BGT226 is highly effective, and NVP-BGT226 represents a potential new candidate for targeted therapy in multiple myeloma. Combined inhibition of PI3K and mammalian target of rapamycin (mTOR) by NVP-BGT226 has been proven to be very effective in terms of induction of apoptosis and inhibition of proliferation. [3] In another study, after 24 hours, 86.9% MiaPaCa-2 100 nM NVP-BGT226 treated cells arrests at the G0/G1 phase compared to 55.6% of control cells. [4]

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 and 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 of 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) or the control. [2]

Protocol (from reference)

Cell Research:[3]
  • Cell lines: NCI-H929, U266, RPMI-8226 and OPM2 MM cells
  • Concentrations: 20-250 nM
  • Incubation Time: 36 hours
  • Method: NCI-H929, U266, RPMI-8226 and OPM2 MM cells are seeded in 96-well plates at a concentration of 1.5 × 104 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 another 12 hours in a humidified atmosphere (37 °C/5% CO2). Then, the plates are centrifuged (10 min, 300 g), and 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 °C. The cells are washed three times with medium and incubated with anti-BrdU-POD labelling solution for 30 min at 37 °C. The anti-POD solution is removed and the cells are washed three times with washing buffer. The ABTS substrate solution is added, and absorbance is measured in a microplate reader at 405 nm with a reference wave length of 490 nm.
Animal Research:[2]
  • Animal Models: Human FaDu xenografted mice
  • Dosages: 5 mg/kg for 3 weeks
  • Administration: Oral administration

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 650.6
Formula

C28H25F3N6O2.C4H4O

CAS No. 1245537-68-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1C2=CN=C3C=CC(=CC3=C2N(C1=O)C4=CC(=C(C=C4)N5CCNCC5)C(F)(F)F)C6=CN=C(C=C6)OC.C(=CC(=O)O)C(=O)O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00742105 Terminated Drug: BGT226 Cancer|Solid Tumor|Advanced Solid Tumor Novartis Pharmaceuticals|Novartis November 17 2008 Phase 1
NCT00600275 Completed Drug: BGT226 Solid Tumors|Breast Cancer|Cowden Syndrome Novartis Pharmaceuticals|Novartis December 2007 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
In the case to dissolve NVP-BGT226 for in vivo study , this solvent - 30% PEG400+0.5% Tween80+5% Propylene glycol is used as suggested by Selleck Chem. May I know how to prepare this solvent? Do I need to mix the above three into water, saline or DMSO or other solutions?

Answer:
S2749 BGT226 (NVP-BGT226) can be dissolved in 30% PEG400+0.5% Tween80+5% Propylene glycol at 30mg/ml as a suspension for oral gavage. When prepare the solution, please add PEG 400 and Propylene glycol to the drug first. Please sonicate and warm it at about 45-50 degree to dissolve the drug as much as possible. Then add Tween, and mix the them homogeneously. Then dilute with water.

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