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Purity: ≥98%
Bemcentinib (formerly known as BGB324; R428) is a novel, potent and selective inhibitor of the RTK (receptor tyrosine kinase) Axl with potential anticancer activity. With an IC50 of 14 nM, it inhibits Axl and exhibits >100-fold greater selectivity for Axl than Abl. Rat models of metastatic breast cancer demonstrated high activity of R428 in preventing tumor spread and extending survival. R428's selective Axl blockade has therapeutic value in extending the survival of animals with metastatic tumors because Axl signaling controls breast cancer metastasis at multiple levels in tumor cells and tumor stromal cells.
| Targets |
Axl kinase (IC50 = 14 nM)
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| ln Vitro |
Bemcentinib (R428) (2μM) is comparable to Axl knockdown in its ability to significantly inhibit the migration and invasion mechanisms of Axlpos melanoma cells[1]. In order to improve the inhibition of liver micrometastasis, bemcentinib (R428) works in concert with CDDP#2. As demonstrated by decreased lipid uptake, bemcentinib (R428) (50 nM-1μM) inhibits preadipocyte differentiation into mature adipocytes in a concentration-dependent manner[3].
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| ln Vivo |
After being cultured in serum-free medium for 24 hours, cells are taken out and added to the upper chamber (1.5 x 10^5 cells per well) of 24-well chambers that are either uncoated (for migration) or coated with matrigel (for invasion). The lower chamber is filled with 10% fetal bovine serum RPMI medium. Before the cells are loaded into the upper chambers, they are treated for two hours with either the vehicle (DMSO, 0.25%) or bemcentinib (R428) (2 μM). The medication or vehicle is present in both the upper and lower chambers. Using a 480/520 nm filter set on an Infinite M1000 microplate reader, the fluorescent signals of migrating or invading cells are measured 20 or 42 hours later, respectively.
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| Enzyme Assay |
R428 (also known as BGB324) is a powerful and selective Axl inhibitor that is >100-fold more selective for Axl than Abl, with an IC50 of 14 nM. Additionally, R428 has a higher selectivity for Axl than Mer and Tyro3 (50–100 fold more selective) as well as InsR, EGFR, HER2, and PDGFRβ (100–fold more selective). In radiometric in vitro kinase assays, a five-point R428 dose titration was carried out on 133 kinases at the KmATP for each kinase. A fluorescence polarization protocol was also used for the Axl, Mer, and Tyro3 (Carna Biosciences) assays. With the Z-LYTE assay, HER2 activity was ascertained.
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| Cell Assay |
After being cultured in serum-free medium for 24 hours, cells are taken out and added to the upper chamber (1.5 x 10^5 cells per well) of 24-well chambers that are either uncoated (for migration) or coated with matrigel (for invasion). The lower chamber is filled with 10% fetal bovine serum RPMI medium. Before the cells are loaded into the upper chambers, they are treated for two hours with either the vehicle (DMSO, 0.25%) or bemcentinib (R428) (2 μM). The medication or vehicle is present in both the upper and lower chambers. Using a 480/520 nm filter set on an Infinite M1000 microplate reader, the fluorescent signals of migrating or invading cells are measured 20 or 42 hours later, respectively.
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| Animal Protocol |
Female NCr nu/nu mice aged seven to eight weeks are given intracardial injections of bioluminescent MDA-MB-231-luc-D3H2LN cell suspension. Two hours prior to cell implantation, oral dosage of Bemcentinib (R428) (125 mg/kg, p.o.) or vehicle is administered twice daily until day 21 (n=20). Day 22 in vivo bioluminescence imaging is used to measure the metastatic burden, and the Wilcoxon rank sum test is used for analysis.
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| References |
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| Molecular Formula |
C30H34N8
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| Molecular Weight |
506.64
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| Exact Mass |
506.29
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| Elemental Analysis |
C, 71.12; H, 6.76; N, 22.12
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| CAS # |
1037624-75-1
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| Related CAS # |
1037624-75-1; 1037624-91-1 (racemic);
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| Appearance |
Solid powder
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| SMILES |
C1CCN(C1)[C@H]2CCC3=C(CC2)C=C(C=C3)NC4=NN(C(=N4)N)C5=NN=C6C(=C5)CCCC7=CC=CC=C76
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| InChi Key |
KXMZDGSRSGHMMK-VWLOTQADSA-N
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| InChi Code |
InChI=1S/C30H34N8/c31-29-33-30(32-24-13-10-20-11-14-25(15-12-22(20)18-24)37-16-3-4-17-37)36-38(29)27-19-23-8-5-7-21-6-1-2-9-26(21)28(23)35-34-27/h1-2,6,9-10,13,18-19,25H,3-5,7-8,11-12,14-17H2,(H3,31,32,33,36)/t25-/m0/s1
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| Chemical Name |
1-(3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl)-3-N-[(7S)-7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-1,2,4-triazole-3,5-diamine
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.11 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 sonication.
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. Solubility in Formulation 2: 5% DMSO+corn oil: 1 mg/mL View More
Solubility in Formulation 3: 12.5 mg/mL (24.67 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 5 mg/mL (9.87 mM) in 0.5%HPMC 1%Tween80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9738 mL | 9.8689 mL | 19.7379 mL | |
| 5 mM | 0.3948 mL | 1.9738 mL | 3.9476 mL | |
| 10 mM | 0.1974 mL | 0.9869 mL | 1.9738 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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A, experimental protocol for MDA-MB-231-luc-D3H2LN metastasis prevention study.Cancer Res.2010 Feb 15;70(4):1544-54. |
A, experimental protocol for 4T1 orthotopic metastasis study.Cancer Res.2010 Feb 15;70(4):1544-54. |
R428 modulates expression of Snail and GM-CSF in 4T1 primary tumors.Cancer Res.2010 Feb 15;70(4):1544-54. |
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