Motixafortide (BL-8040)

Catalog No.S9665 Synonyms: BKT140, TF 14016, 4-fluorobenzoyl, 4F-benzoyl-TN14003, T140

For research use only.

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

Motixafortide (BL-8040) Chemical Structure

CAS No. 664334-36-5

Purity & Quality Control

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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. BL-8040 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 BL-8040 induces the robust mobilization of AML blasts from the BM. In addition, AML cells exposed to BL-8040 undergoes differentiation. 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. 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

BL-8040 induces the apoptosis of AML cells in vivo. Treatment with a BCL-2 inhibitor induces apoptosis and acts together with BL-8040 to enhance cell death. BL-8040 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 Research:

[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 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.

Animal Research:

[1]

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

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 2159.52
Formula

C97H144FN33O19S2

CAS No. 664334-36-5
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CC2C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N2C1)CCCCN)CCCCN)CCCNC(=O)N)CC3=CC=C(C=C3)O)NC(=O)C(CC4=CC5=CC=CC=C5C=C4)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C6=CC=C(C=C6)F)C(=O)NC(CCCNC(=N)N)C(=O)N)CCCNC(=O)N)CCCNC(=N)N)CC7=CC=C(C=C7)O

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02763384 Recruiting Drug: BL-8040|Drug: Nelarabine T-Acute Lymphoblastic Leukemia|Adult T Lymphoblastic Lymphoma Washington University School of Medicine|The Leukemia and Lymphoma Society|National Institutes of Health (NIH)|National Cancer Institute (NCI) December 2 2016 Phase 2
NCT02115672 Withdrawn Drug: BL-8040 Chronic Myeloid Leukemia Sheba Medical Center November 2014 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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