LY2510924 is a potent and selective CXCR4 antagonist that blocks SDF-1 binding to CXCR4 with an IC50 of 0.079 nM.
Description :
LY-2510924 (LY2510924) is a potent and selective, cyclic peptide CXCR4 antagonist with IC50 of 0.079 nM, without apparent agonist activity; inhibits SDF-1-induced cell migration with IC50 of 0.26 nM and inhibits SDF-1/CXCR4-mediated intracellular signaling; exhibits inhibition of SDF-1-stimulated phospho-ERK and phospho-Akt in tumor cells; shows inhibition of tumor growth in human xenograft models with acceptable in vivo stability and a pharmacokinetic profile.
Kidney Cancer
In human lymphoma U937 cells expressing endogenous CXCR4, LY2510924 inhibits SDF-1-induced cell migration with IC50 value of 0.26 nmol/L and inhibits SDF-1/CXCR4-mediated intracellular signaling. LY2510924 exhibits a concentration-dependent inhibition of SDF-1-stimulated phospho-ERK and phospho-Akt in tumor cells. Biochemical and cellular analyses reveal that LY2510924 has no apparent agonist activity. LY2510924 has no inhibitory activities against other chemokine receptors including CCR1, CCR2, CXCR2, and CXCR3 at the concentrations tested. Similarly, there is no activity observed among serotonin, dopamine, and opioid receptors[1].
LY2510924 chiefly inhibits the proliferation of AML cells with little induction of cell death and reduces protection against chemotherapy by stromal cells[1]. LY2510924 specifically blocks SDF-1 binding to CXCR4 with IC50 value of 0.079 nM, and inhibits SDF-1–induced GTP binding with Kb value of 0.38 nM. In human lymphoma U937 cells expressing endogenous CXCR4, LY2510924 inhibits SDF-1–induced cell migration with IC50 value of 0.26 nM and inhibits SDF-1/CXCR4-mediated intracellular signaling. LY2510924 exhibits a concentration-dependent inhibition of SDF-1–stimulated phospho-ERK and phospho-Akt in tumor cells. Biochemical and cellular analyses reveals that LY2510924 has no apparent agonist activity[2].