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| 10mg |
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| Targets |
NVP-BGG463 targets cyclin-dependent kinase 2 (CDK2) as a Type II kinase inhibitor. Type II kinase inhibitors bind to the inactive conformation of the kinase, providing selectivity. The compound also inhibits T315I BCR-ABL autophosphorylation, indicating activity against the BCR-ABL fusion protein that drives CML.
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| ln Vitro |
In CML mice models, BGG463 works well to block T315I BCR-ABL autophosphorylation and exhibits good oral effectiveness [2].
NVP-BGG463 potently inhibits T315I BCR-ABL autophosphorylation in vitro. Its in vitro activity is assessed by measuring inhibition of CDK2 kinase activity and BCR-ABL autophosphorylation in cell-free and cellular assays. The compound's Type II kinase inhibitor mechanism provides selectivity for the inactive kinase conformation. |
| ln Vivo |
In vivo activity of NVP-BGG463 has been demonstrated in mouse models of chronic myeloid leukemia (CML). As an orally bioactive compound, it shows good oral efficacy in these models. Its in vivo activity is assessed by measuring inhibition of tumor growth and BCR-ABL signaling in CML models.
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| Enzyme Assay |
The in vitro enzyme assay for NVP-BGG463 involves measuring its inhibitory activity against CDK2 and BCR-ABL kinases in cell-free systems. These assays use purified kinase enzymes and measure the phosphorylation of substrate peptides in the presence of the compound. Inhibitory potency is determined by assessing kinase inhibition. The compound's Type II binding mode is characterized by its interaction with the inactive kinase conformation.
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| Cell Assay |
In vitro cellular assays for NVP-BGG463 are performed using cancer cell lines, particularly those expressing BCR-ABL. These assays measure the compound's ability to inhibit BCR-ABL autophosphorylation and cell proliferation. The compound's effects on CDK2-mediated phosphorylation are also assessed.
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| Animal Protocol |
In vivo animal studies for NVP-BGG463 are conducted in mouse models of CML. These studies typically involve oral administration of the compound, followed by assessment of tumor growth inhibition, BCR-ABL phosphorylation, and survival. The compound's oral efficacy is evaluated in these models.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NVP-BGG463 are characterized by oral bioavailability. The compound has a molecular formula of C₃₀H₂₉F₃N₈O₃ and a molecular weight of 578.58 g/mol. It is supplied as a solid powder. Its solubility in DMSO is 0.1-1 mg/mL and in methanol is 1-10 mg/mL. Its pharmacokinetic profile supports oral dosing.
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| Toxicity/Toxicokinetics |
Toxicology studies of NVP-BGG463 have been conducted to support its development as an anticancer agent. As a CDK2 and BCR-ABL inhibitor, its toxicology profile includes effects on rapidly dividing cells and potential for cardiotoxicity. The compound's Type II kinase inhibitor mechanism may provide improved selectivity and safety.
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| References | |
| Additional Infomation |
NVP-BGG463 (CAS: 890129-26-7) is a novel Type II kinase inhibitor targeting CDK2. It potently inhibits T315I BCR-ABL autophosphorylation and shows good oral efficacy in mouse models of CML. The compound has a molecular formula of C₃₀H₂₉F₃N₈O₃ and a molecular weight of 578.58 g/mol. It is for research use only.
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| Molecular Formula |
C30H29F3N6O3
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|---|---|
| Molecular Weight |
578.584876775742
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| Exact Mass |
578.225
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| CAS # |
890129-26-7
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| PubChem CID |
67406169
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
669.0±55.0 °C at 760 mmHg
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| Flash Point |
358.4±31.5 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
4.96
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
42
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| Complexity |
917
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=O)NC1=CC(=NC=N1)OC2=CC3=C(C=C2)C(=CC=C3)C(=O)NC4=CC(=C(C=C4)CN5CCN(CC5)C)C(F)(F)F
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| InChi Key |
MZZJNOOADWVFPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H29F3N6O3/c1-19(40)36-27-16-28(35-18-34-27)42-23-8-9-24-20(14-23)4-3-5-25(24)29(41)37-22-7-6-21(26(15-22)30(31,32)33)17-39-12-10-38(2)11-13-39/h3-9,14-16,18H,10-13,17H2,1-2H3,(H,37,41)(H,34,35,36,40)
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| Chemical Name |
6-(6-acetamidopyrimidin-4-yl)oxy-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide
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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 : ≥ 125 mg/mL (~216.05 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.60 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 20.8 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: ≥ 2.08 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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: ≥ 2.08 mg/mL (3.60 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 | 1.7284 mL | 8.6418 mL | 17.2837 mL | |
| 5 mM | 0.3457 mL | 1.7284 mL | 3.4567 mL | |
| 10 mM | 0.1728 mL | 0.8642 mL | 1.7284 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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