| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
IC50: PI3Kδ:35 nM; PI3Kα:56 nM; PI3Kγ:117 nM; PI3Kβ:446 nM; PDK1:240 nM; VEGFR1:2.56 μM
NVP-BAG956 targets phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1). It inhibits PI3Kδ, PI3Kα, PI3Kγ, and PI3Kβ with IC₅₀ values of 34, 56, 112, and 444 nM, respectively. It inhibits PDK1 with an IC₅₀ of 245 nM. It acts as an ATP-competitive inhibitor. |
|---|---|
| ln Vitro |
NVP-BAG956 has an IC50 of 240/260 nM and inhibits PDK1 as well. VEGFR1 is likewise inhibited by NVP-BAG956, with an IC50 of 2.56±0.56 μM.nM. NVP-BAG956 (IC50=290±20 nM)-induced inhibition of PKB/Akt phosphorylation was associated with decreased A2058 cell proliferation. NVP-BAG956 causes A2058 cells to only be able to exit G2-M and stay in G1. NVP-BAG956 clearly induces the expression of p27 Kip1 in A2058 cells, but not in C32 cells[1].
In vitro, NVP-BAG956 inhibits cellular AKT phosphorylation at Thr308 in A2058 cells with an IC₅₀ of 67±25 nM. Inhibition of PKB/Akt phosphorylation correlates with loss of cell proliferation (IC₅₀ = 290±20 nM). It blocks cell proliferation and causes arrest in the G1 phase of the cell cycle. |
| ln Vivo |
In vivo, NVP-BAG956 has demonstrated anticancer activity in preclinical models. By inhibiting PI3K and PDK1, it suppresses tumor growth and proliferation. It has been studied for the treatment of various cancers, including melanoma.
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| Enzyme Assay |
The in vitro kinase assay for NVP-BAG956 measures the inhibition of PI3K and PDK1 kinase activity. Recombinant enzymes are incubated with the compound and substrates in the presence of ATP. The phosphorylation of substrates is quantified. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
One day after plating (7×103 cells/cm2), melanoma cells (A2058, B16F1, B16F10, C32, HBL, Malme, Malme3M, NA8, SKMel2, SKMel23, A375, Hs294T, WM35, and 1205lu cells) are exposed to LY294002 (25 μM), Wortmannin (500 nM), NVP-BAG956 (1 μM), NVP-BBD130 (1 μM), NVP-BEZ235 (1 μM), and ZSTK474 (1 μM), and Rapamycin (100 nM). Compound concentrations are set 2 log units above the IC50 in vitro to ensure full PI3K inhibition, except for the μM inhibitor LY294002. Cells are trypsinized and counted, and the volume is quantified using a Casy Counter and Analyser. To determine the nuclear volume, cells are resuspended in CASYton containing 0.5% Triton X-100, followed by repetitive pipetting (8×), before volume measurements[1].
In vitro cell-based assays for NVP-BAG956 are performed using cancer cell lines such as A2058 melanoma cells. Cells are treated with the compound, and cell proliferation is measured. AKT phosphorylation at Thr308 is assessed by Western blotting. Cell cycle analysis is performed to determine the phase of arrest. |
| Animal Protocol |
In vivo animal experiments for NVP-BAG956 have been conducted in xenograft models of various cancers. Animals are administered the compound orally or via other routes, and tumor growth inhibition is measured. Pharmacodynamic markers such as AKT phosphorylation are assessed in tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NVP-BAG956 have been characterized in preclinical species. It is orally bioavailable and achieves sufficient plasma concentrations to exert its pharmacological effects. Detailed PK parameters such as half-life, clearance, and bioavailability are determined from plasma concentration-time profiles.
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| Toxicity/Toxicokinetics |
Toxicological data for NVP-BAG956 are limited as it is a research compound. In standard preclinical safety assessments, it would be evaluated for potential off-target effects and general toxicity. The compound is intended for research use only and not for therapeutic use in humans.
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| References | |
| Additional Infomation |
NVP-BAG956 is a dual PI3K/PDK1 inhibitor that has been studied for the treatment of cancer. It has shown potent activity in preclinical models of melanoma and other cancers. It has not been approved for clinical use and remains an investigational research compound.
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| Molecular Formula |
C28H21N5
|
|---|---|
| Molecular Weight |
427.49984
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| Exact Mass |
427.179
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| CAS # |
853910-02-8
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| PubChem CID |
24882589
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
694.8±65.0 °C at 760 mmHg
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| Flash Point |
374.0±34.3 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.655
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| LogP |
4.75
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
806
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HSQAARMBHJCUOK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H35ClN2O2/c25-22-5-4-17(3-1-6-26-7-2-8-28)12-21(22)23(29)27-16-24-13-18-9-19(14-24)11-20(10-18)15-24/h4-5,12,18-20,26,28H,1-3,6-11,13-16H2,(H,27,29)
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| Chemical Name |
Benzamide, 2-chloro-5-(3-((3-hydroxypropyl)amino)propyl)-N-(tricyclo(3.3.1.13,7)dec-1-ylmethyl)-
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| Synonyms |
NVP-BAG956; BAG-956; NVP-BAG-956; BAG 956; NVP-BAG 956; BAG956;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~116.96 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.85 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3392 mL | 11.6959 mL | 23.3918 mL | |
| 5 mM | 0.4678 mL | 2.3392 mL | 4.6784 mL | |
| 10 mM | 0.2339 mL | 1.1696 mL | 2.3392 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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