Motixafortide (BL-8040)

Catalog No.S9665 Batch:S966501

Technical Data

Formula	C₉₇H₁₄₄FN₃₃O₁₉S₂
Molecular Weight	2159.52	CAS No.	664334-36-5
Solubility (25°C)*	In vitro	Water	100 mg/mL (46.3 mM)


* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Motixafortide (BL-8040, BKT140, TF 14016, 4-fluorobenzoyl, 4F-benzoyl-TN14003, T140) is an antagonist of CXCR4 with IC50 of ～1 nM. This compound induces the apoptosis of AML blasts by down-regulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression.

Targets

ERK ^[1]	Bcl-2 ^[1]	MCL-1 ^[1]	cyclin-D1 ^[1]	CXCR4 ^[1] (Cell-free assay)
				1 nM

In vitro

Treatment with Motixafortide (BL-8040) induces the robust mobilization of AML blasts from the BM. In addition, AML cells exposed to this compound undergo differentiation. It also 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. Overexpression of miR-15a/miR-16-1 directly induces leukemic cell death. BL-8040-induced apoptosis is also mediated by the inhibition of survival signals via the AKT/ERK pathways.^[1]

In vivo

Motixafortide (BL-8040) induces the apoptosis of AML cells in vivo. Treatment with a BCL-2 inhibitor induces apoptosis and acts together with it to enhance cell death. This compound also synergizes with FLT3 inhibitors to induce AML cell death. Importantly, this combined treatment prolongs the survival of tumor-bearing mice and reduces minimal residual disease in vivo.^[1]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines The leukemic cell lines (MV4-11, THP-1, U937, HL-60) Concentrations 0.1 μM, 1 μM, 10 μM, 20 μM Incubation Time 24 h, 48 h 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 Motixafortide (BL-8040)/AMD3100 (0.1, 1, 10 or 20μM) or ABT-199 (0.01, 0.1, 1 or 10μM). To test the combination of this compound and ABT-199, cells are incubated for 24hr with it (20μM) and ABT-199 (0.01, 0.1, 1 or 10μM). To test the combined effects of the compound and AC220, cells are incubated for 48 hr with it (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.
Animal Study:^{^[1]}	Animal Models female NOD scid gamma (NSG) mice (7-9 weeks old) Dosages 400 μg/mouse Administration SC

Cell Assay:^{^[1]}

Cell lines
The leukemic cell lines (MV4-11, THP-1, U937, HL-60)
Concentrations
0.1 μM, 1 μM, 10 μM, 20 μM
Incubation Time
24 h, 48 h
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 Motixafortide (BL-8040)/AMD3100 (0.1, 1, 10 or 20μM) or ABT-199 (0.01, 0.1, 1 or 10μM). To test the combination of this compound and ABT-199, cells are incubated for 24hr with it (20μM) and ABT-199 (0.01, 0.1, 1 or 10μM). To test the combined effects of the compound and AC220, cells are incubated for 48 hr with it (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.

Animal Study:^{^[1]}

Animal Models
female NOD scid gamma (NSG) mice (7-9 weeks old)
Dosages
400 μg/mouse
Administration
SC

References

https://pubmed.ncbi.nlm.nih.gov/28280274/

Selleck's Motixafortide (BL-8040) Has Been Cited by 1 Publication

Modelling glioblastoma migration with patient-derived cells, human iPSC-derived cortical neural spheroid, and high-content imaging [ King's College London, 2023, ]	PubMed: None

Modelling glioblastoma migration with patient-derived cells, human iPSC-derived cortical neural spheroid, and high-content imaging [ King's College London, 2023, ]

PubMed: None

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SHIPPING AND STORAGE
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