Name: R428
Price: 315.00 USD

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    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.
    
    [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.
- Properties
  - Alternative Name
    
    R-428; R 428; BGB324; Bemcentinib; 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
    
    CAS Number
    
    1037624-75-1
    
    Molecular Formula
    
    C30H34N8
    
    Molecular Weight
    
    506.64
    
    Appearance
    
    A solid
    
    Purity
    
    99.87%
    
    Solubility
    
    ≥25 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Nil Vanli, Jinghao Sheng, et al. "Ribonuclease 4 is associated with aggressiveness and progression of prostate cancer." Commun Biol. 2022 Jun 25;5(1):625. PMID: 35752711
    2. Samuel D. Zwernik, Beau H. Adams, et al. "AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines." Mol Ther Oncolytics. 2021 Nov 11;23:447-457. PMID: 34901388
    3. Sekyu Choi, Bing Zhang, et al. "Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence." Nature. 2021 Apr;592(7854):428-432. PMID: 33790465
    4. Qi Bian, Joshua C. Anderson, et al. "Mesangioproliferative Kidney Diseases and Platelet-Derived Growth Factor–Mediated AXL Phosphorylation." Kidney Medicine.Available online 30 July 2021.
    5. Afnan Abu-Thuraia, Marie-Anne Goyette, et al. "AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network." Nat Commun. 2020 Jul 17;11(1):3586. PMID: 32681075
    6. McDaniel NK, Iida M, et al. "AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer." Clin Cancer Res. 2020;10.1158/1078-0432.CCR-19-3142. PMID: 32439698
    7. Tsai KYF, Hirschi Budge KM, et al. "RAGE and AXL expression following secondhand smoke (SHS) exposure in mice." Exp Lung Res. 2019 Nov - Dec;45(9-10):297-309. PMID: 31762322
    8. Hirschi KM, Tsai KYF, et al. "Growth Arrest Specific Protein (Gas)-6/AXL Signaling Induces Preeclampsia (PE) in Rats." Biol Reprod. 2019 Jul 26. pii: ioz140. PMID: 31347670
    9. Goyette MA, Cusseddu R, et al. "AXL knockdown gene signature reveals a drug repurposing opportunity for a class of antipsychotics to reduce growth and metastasis of triple-negative breast cancer." Oncotarget. 2019 Mar 12;10(21):2055-2067. PMID: 31007848
    10. Chen F, Song Q, et al. "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
    11. 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
    12. 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
    13. 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
    14. 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
    15. 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
    16. 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
    17. 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
    18. 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
    19. 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