R428Selective Axl inhibitor CAS# 1037624-75-1 |
- Cabozantinib (XL184, BMS-907351)
Catalog No.:BCC1264
CAS No.:849217-68-1
Quality Control & MSDS
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| Cas No. | 1037624-75-1 | SDF | Download SDF |
| PubChem ID | 46215462 | Appearance | Powder |
| Formula | C30H34N8 | M.Wt | 506.64 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | BGB324; Bemcentinib | ||
| Solubility | DMSO : 10.25 mg/mL (20.23 mM; Need ultrasonic and warming) | ||
| Chemical Name | 1-(6,7-dihydro-5H-benzo[2,3]cyclohepta[2,4-d]pyridazin-3-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 | ||
| SMILES | C1CCN(C1)C2CCC3=C(CC2)C=C(C=C3)NC4=NN(C(=N4)N)C5=NN=C6C(=C5)CCCC7=CC=CC=C76 | ||
| Standard InChIKey | KXMZDGSRSGHMMK-VWLOTQADSA-N | ||
| Standard InChI | 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. | |||||
| Targets | Axl | |||||
| IC50 | 14 nM | |||||
| Cell experiment:[1] | |
| Cell lines | MDA-MB-231 cells, 4T1 cells and Hela cells. |
| Preparation method | TThe solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
| Reacting condition | Five-point R428 dose titration (≤ 10 μM); Cells were preincubated with R428 for 3 h. |
| Applications | R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. |
| Animal experiment:[2] | |
| Animal models | Female BALB/c mice were inoculated in the mammary fat pad with 0.5 × 106 4T1 cells. |
| Dosage form | Oral dosing with R428 (7–75 mg/kg twice daily) or vehicle continued until days 19 to 21. |
| Applications | Oral administration of R428 displayed a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. R428 administration reduced metastatic burden and extended survival in MDAMB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis. |
| Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| References: [1]. Holland SJ, Pan A, Franci C et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res. 2010 Feb 15;70(4):1544-54. | |
R428 Dilution Calculator
R428 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9738 mL | 9.8689 mL | 19.7379 mL | 39.4758 mL | 49.3447 mL |
| 5 mM | 0.3948 mL | 1.9738 mL | 3.9476 mL | 7.8952 mL | 9.8689 mL |
| 10 mM | 0.1974 mL | 0.9869 mL | 1.9738 mL | 3.9476 mL | 4.9345 mL |
| 50 mM | 0.0395 mL | 0.1974 mL | 0.3948 mL | 0.7895 mL | 0.9869 mL |
| 100 mM | 0.0197 mL | 0.0987 mL | 0.1974 mL | 0.3948 mL | 0.4934 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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R428 is a selective Axl inhibitor with an IC50 of 14 nM, more than 50-fold sensitivity for Axl than Abl, Mer, Tyro3, InsR, EGFR, HER2, and PDGFR.
Axl receptor tyrosine kinase transduces signals from extracellular matrix into cytoplasma by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). It is involved in several cellular processes including growth, migration, aggregation and anti-inflammation.
R428 blocks the catalytic activity of Axl, at low nanomolar concentration. [1] Axl-dependent activities, including Akt phosphorylation, cell invasion, proinflammatory cytokine production are inhibited. R428 administration reduces the expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. It also inhibits angiogenesis, reduces metastatic tumor burden and extends survival in animal xenograft models. In addition, R428 synergizes with cisplatin to enhance suppression of liver micrometastasis.
R428 can be administrated orally.
References:
[1]Holland SJ, Pan A, Franci C, et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolong survival in models of metastatic breast cancer. Cancer Res 2010. 70(4): 1544-1554.
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R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer.[Pubmed:20145120]
Cancer Res. 2010 Feb 15;70(4):1544-54.
Accumulating evidence suggests important roles for the receptor tyrosine kinase Axl in cancer progression, invasion, metastasis, drug resistance, and patient mortality, highlighting Axl as an attractive target for therapeutic development. We have generated and characterized a potent and selective small-molecule inhibitor, R428, that blocks the catalytic and procancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. Pharmacologic investigations revealed favorable exposure after oral administration such that R428-treated tumors displayed a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, R428 inhibited angiogenesis in corneal micropocket and tumor models. R428 administration reduced metastatic burden and extended survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis. Additionally, R428 synergized with cisplatin to enhance suppression of liver micrometastasis. Our results show that Axl signaling regulates breast cancer metastasis at multiple levels in tumor cells and tumor stromal cells and that selective Axl blockade confers therapeutic value in prolonging survival of animals bearing metastatic tumors.
