Uses
LDN-211904 oxalate is a potent and reversible EphB3 inhibitor with an IC50 of 79 nM. LDN-211904 oxalate shows good metabolic stability in mouse liver microsomes. LDN-211904 oxalate with Cetuximab (HY-P9905) could be effective in inhibiting STAT3-activated colorectal cancer (CRC) stemness and Cetuximab resistance in CRC[1][2].
Biological Activity
ldn-211904 is an inhibitor of erythropoietin-producing hepatocellular carcinoma (eph) receptors.erythropoietin-producing hepatocellular carcinoma (eph) receptors, a group of highly conserved transmembrane proteins composed of multiple domains, participate in various cell signaling pathways. so far, 16 eph receptors have been identified in vertebrates, which can be divided into two major classes (epha and ephb) based on sequence similarity. mammals including humans have 14 eph receptors (epha1–epha8, epha10, ephb1–ephb4 and ephb6).
in vitro
previous study found that ldn-211904, a 4-piperidinyl analog, retained significant ephb3 inhibitory activity, and also had greater aqueous solubility due to the presence of a basic amine. ldn-211904 was profiled for functional inhibitory activity against a panel of 288 kinases and the results showed that ldn-211904 was quite selective for tyrosine kinases. the only noted exceptions were the three serine/threonine kinases p38a, p38b, and qik. in addition, only ldn-211904 showed moderate selectivity among the tyrosine kinases and little selectivity verses other epha and ephb subtypes, except for epha6 and epha7. moreover, ldn-211904 demonstrated the best stability with a t1/2 of 348 min and a clint of 4 μl/min/mg protein [1].
in vivo
LDN-211904 (0.1 mg/kg; i.p.; three times a week; for 21 days) oxalate inhibits and overcomes Cetuximab (HY-P9905) resistance in vivo[2].
| Animal Model: | Four-week-old female BALB/c nude mice were implanted subcutaneously SW48 cells[2] |
| Dosage: |
0.1 mg/kg |
| Administration: | i.p.; three times a week; for 21 days |
| Result: | Inhibited tumor growth. |
References
[1] qiao, l. ,choi, s.,case, a., et al. structure-activity relationship study of ephb3 receptor tyrosine kinase inhibitors. bioor. med. chem. lett. 19(21), 6122-6126 (2009).
