LY2510924 is a potent and selective CXCR4 antagonist, which blocks SDF-1 binding to CXCR4 with IC50 of 0.079 nM. LY2510924 inhibits SDF-1-induced cell migration (IC50 = 0.26 nM) in human lymphoma U937 cells expressing endogenous CXCR4. LY2510924 chiefly inhibits the proliferation of AML cells with little induction of cell death and reduces protection against chemotherapy by stromal cells.
|Cell lines||U937 cells|
|Preparation method||Briefly, U937 cells were harvested and washed once with chemotaxis assay buffer prepared with 1× RPMI medium containing 10 mmol/L HEPES, pH 7.5, and 0.3% BSA. Cells were then resuspended in assay buffer at a density of 5 × 106 cells/mL. The assay was performed in a 96-well ChemoTx plate (NeuroProbe). Generally, 50 μL of cell mixture with or without LY2510924 was plated on the upper chamber, and 30 μL of SDF-1α (10 ng/mL) prepared in 1× chemotaxis buffer was added to the lower chamber. The plate was then incubated for 2.5 hours at 37°C. Following the incubation, 5 μL of CellTiter 96 AQ (Promega) was added into the lower chamber. The plate was then incubated for 60 minutes at 37°C. The migrated cells were detected by measuring the absorbance at 492 nm with a Tecan Spectrafluor Plus Microplate Reader.|
|Incubation time||2.5 h|
|Animal models||female C57/BL6 mice, male Sprague-Dawley rats, male Beagle dogs, and male Cynomolgus monkeys at fasted state|
|Formulation||formulated in 1× PBS|
|Administration||s.c. or i.v.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||Water 45 mg/mL
DMSO 120 mg/mL
Antileukemia activity of the novel peptidic CXCR4 antagonist LY2510924 as monotherapy and in combination with chemotherapy
Byung-Sik Cho, et al. Blood. 2015 Jul 9;126(2):222-32. PMID: 26031918.
Identification of LY2510924, a novel cyclic peptide CXCR4 antagonist that exhibits antitumor activities in solid tumor and breast cancer metastatic models
Sheng-Bin Peng, et al. Mol Cancer Ther. 2015 Feb;14(2):480-90. PMID: 25504752.
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