Motixafortide (BL-8040) is an antagonist of CXCR4 with IC50 value of 1 nM. Motixafortide (BL-8040) specifically triggers CXCR4-dependent cell death in leukemia and MM cells and it stimulates apoptotic cell death in leukemia and MM cells. Treatment with Motixafortide (BL-8040) can overcome IL-6 dependent proliferation and survival of ARH77 MM cells. BL-8040 induces the apoptosis of AML cells in vitro. This apoptosis is mediated by the up-regulation of miR-15a/miR-16-1, resulting in down-regulation of the target genes BCL-2, MCL-1 and cyclin-D1.
|Cell lines||The leukemic cell lines (MV4-11, THP-1, U937, HL-60)|
|Preparation method||Cells are seeded in triplicate at 2×105 cells/well in a total volume of 250 μl in a 96-well plate in medium supplemented with 1% FCS RPMI medium for 24hr in the presence of BL-8040/AMD3100 (0.1, 1, 10 or 20μM) or ABT-199 (0.01, 0.1, 1 or 10μM). To test the combination of BL-8040 and ABT-199, cells are incubated for 24hr with BL-8040 (20μM) and ABT-199 (0.01, 0.1, 1 or 10μM). To test the combined effects of BL-8040 and AC220, cells are incubated for 48 hr with BL-8040 (20μM), AC220 (50nM) or a combination of the two. After incubation, cells are stained with propidium iodide (PI), and the percentage of dead cells (PI+ cells) in the culture is measured using a FACSCalibur machine.|
|Concentrations||0.1 μM, 1 μM, 10 μM, 20 μM|
|Incubation time||24 h, 48 h|
|Animal models||female NOD scid gamma (NSG) mice (7-9 weeks old)|
|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 90 mg/mL|
The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by downregulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression
M Abraham, et al. Leukemia. 2017 Nov;31(11):2336-2346. PMID: 28280274.
The high-affinity CXCR4 antagonist BKT140 is safe and induces a robust mobilization of human CD34+ cells in patients with multiple myeloma
Amnon Peled, et al. Clin Cancer Res. 2014 Jan 15;20(2):469-79. PMID: 24246358.
CXCR4 antagonist 4F-benzoyl-TN14003 inhibits leukemia and multiple myeloma tumor growth
Katia Beider, et al. Exp Hematol. 2011 Mar;39(3):282-92. PMID: 21138752.
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