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| R428Selective Axl inhibitor |
Sample solution is provided at 25 µL, 10mM.
- 1. Chen F, Song Q, Yu Q. "Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition." Am J Cancer Res. 2018 Aug 1;8(8):1466-1482.PMID:30210917
- 2. McDaniel NK, Cummings CT, et al. "MERTK mediates intrinsic and adaptive resistance to AXL-targeting agents." Mol Cancer Ther. 2018 Aug 9. pii: molcanther.1239.2017.PMID:30093568
- 3. Goyette MA, Duhamel S, et al. "The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression." Cell Rep. 2018 May 1;23(5):1476-1490.PMID:29719259
- 4. Zuo Q, Liu J, et al. "AXL/AKT axis mediated-resistance to BRAF inhibitor depends on PTEN status in melanoma."Oncogene. 2018 Mar 19.PMID:29551771
- 5. Sui L, Danzl N, et al. "Beta Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells. Diabetes." 2017 Sep 20. pii: db170120.PMID:28931519
- 6. Xi Y, Kim T, et al. "Local lung hypoxia determines epithelial fate decisions during alveolar regeneration." Nat Cell Biol.2017 Aug;19(8):904-914.PMID:28737769
- 7. Singh PK, Guest JM, et al. "Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes." JCI Insight. 2017 Feb 23;2(4):e92340.PMID:28239662
- 8. Retallack H, Di Lullo E, et al. "Zika virus cell tropism in the developing human brain and inhibition by azithromycin." Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14408-14413.PMID:27911847
- 9. Liu S, DeLalio LJ, et al. "AXL-Mediated Productive Infection of Human Endothelial Cells by Zika Virus." Circ Res. 2016 Nov 11;119(11):1183-1189.PMID:27650556
- 10. Tabata T, Petitt M, et al. "Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission. Cell Host Microbe." 2016 Aug 10;20(2):155-66.PMID:27443522
Quality Control & MSDS
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- Purity = 98.61%
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Chemical structure
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| 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 | The 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. |
Reaction Conditions | 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 × 1064T1 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=""> |
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. | |
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| Cas No. | 1037624-75-1 | SDF | Download SDF |
| Synonyms | R-428;R 428;BGB324 | ||
| 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 | ||
| Canonical SMILES | C1CCN(C1)C2CCC3=C(CC2)C=C(C=C3)NC4=NN(C(=N4)N)C5=NN=C6C(=C5)CCCC7=CC=CC=C76 | ||
| Formula | C30H34N8 | M.Wt | 506.64 |
| Solubility | ≥25mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| 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. | ||
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.
