LY2510924

CXCR4

1189.45

DMSO : ≥ 125 mg/mL (105.09 mM)
H2O : ≥ 100 mg/mL (84.07 mM)

powder

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.

LY2510924 has acceptable in vivo stability and a pharmacokinetic profile similar to a typical small-molecular inhibitor in preclinical species. LY2510924 shows dose-dependent inhibition of tumor growth in human xenograft models developed with non-Hodgkin lymphoma, renal cell carcinoma, lung, and colon cancer cells that express functional CXCR4. In MDA-MB-231, a breast cancer metastatic model, LY2510924 inhibits tumor metastasis by blocking migration/homing process of tumor cells to the lung and by inhibiting cell proliferation after tumor cell homing. LY2510924 has a dramatically improved in vivo stability with a half-life of 3 to 5 hours in preclinical species and 9.16 hours in humans at the recommended phase II dose.

C₆₂H₈₈N₁₄O₁₀

1088715-84-7