<Suppliers Price>

Bemcentinib (R428)

Names

[ CAS No. ]:
1037624-75-1

[ Name ]:
Bemcentinib (R428)

[Synonym ]:
1H-1,2,4-Triazole-3,5-diamine, 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N-[(7S)-6,7,8,9-tetrahydro-7-(1-pyrrolidinyl)-5H-benzocyclohepten-2-yl]-
1-(6,7-Dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N-[(7S)-7-(1-pyrrolidinyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]-1H-1,2,4-triazole-3,5-diamine
CS-1046
R428
1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-(7-(S)-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine
BGB324
BGB-324

Biological Activity

[Description]:

Bemcentinib (R428) is a potent and selective inhibitor of Axl with an IC50 of 14 nM.

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> TAM Receptor
Research Areas >> Cancer

[Target]

IC50: 14 nM (Axl kinase)


[In Vitro]

Bemcentinib (R428) (2μM) significantly interferes with mechanisms of migration and invasion of Axlpos melanoma cells at levels comparable to Axl knockdown[1]. Bemcentinib (R428) synergizes with cisplatin to enhance suppression of liver micrometastasis[2]. Bemcentinib (R428) (50 nM-1μM) causes a concentration-dependent inhibition of preadipocyte differentiation into mature adipocytes, as evidenced by reduced lipid uptake[3].

[In Vivo]

Bemcentinib (R428) (125 mg/kg, p.o.) significantly blocks MDA-MB-231-luc-D3H2LN metastases development in two independent mouse models of breast cancer dissemination, suppresses both tumor angiogenesis and vascular endothelial growth factor (VEGF)-induced corneal neovascularization in vivo[2]. Bemcentinib (R428) (75 mg/kg/day, 25 mg/kg twice daily, p.o.) makes mice keep on a high-fat diet resulted in significantly reduced weight gain and subcutaneous and gonadal fat mass[3].

[Cell Assay]

Cells maintained for 24 hours in serum-free medium are harvested and transferred to the upper chamber (1.5×105 cells per well) of uncoated (migration) or matrigel-coated (invasion) 24-well chambers. RPMI medium containing 10% fetal bovine serum is added to the lower chamber. Bemcentinib (R428) (2 μM) or vehicle (DMSO, 0.25%) is added for 2 hours to cells before loading them in the upper chambers. Both the upper and lower chambers contain the drug or vehicle. Quantification of migrating/invading cells is obtained by measuring their fluorescent signals with a 480/520 nm filter set on an Infinite M1000 microplate reader 20 or 42 hours later, respectively.

[Animal admin]

Seven- to 8-wk-old female NCr nu/nu mice are injected intracardially with bioluminescent MDA-MB-231-luc-D3H2LN cell suspension. Oral dosing with Bemcentinib (R428) (125 mg/kg, p.o.) or vehicle twice daily begins 2 h before cell implantation and continue to day 21 (n=20). Metastatic burden is quantified by in vivo bioluminescence imaging on day 22 and analyzed using the Wilcoxon rank sum test.

[References]

[1]. Sensi M, et al. Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase. J Invest Dermatol. 2011 Dec;131(12):2448-57.

[2]. Holland SJ, 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.

[3]. Lijnen HR, et al. Growth arrest-specific protein 6 receptor antagonism impairs adipocyte differentiation and adipose tissue development in mice. J Pharmacol Exp Ther. 2011 May;337(2):457-64.


[Related Small Molecules]

Gilteritinib | BMS-777607 | TP-0903 | LDC1267 | CEP-40783 | SGI-7079 | UNC2250 | 2-D08 | Glesatinib hydrochloride | Ningetinib | NPS-1034 | UNC 2881 | R916562

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
799.6±70.0 °C at 760 mmHg

[ Molecular Formula ]:
C30H34N8

[ Molecular Weight ]:
506.645

[ Flash Point ]:
437.4±35.7 °C

[ Exact Mass ]:
506.290649

[ PSA ]:
98.51000

[ LogP ]:
4.55

[ Vapour Pressure ]:
0.0±2.8 mmHg at 25°C

[ Index of Refraction ]:
1.768

[ Storage condition ]:
-20℃

[ Water Solubility ]:
Insuluble (5.6E-5 g/L) (25 ºC)

Related Compounds