Motixafortide (BL-8040)

Catalog No.S9665 Batch:S966502

Print

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. 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 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 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 Study:

[1]
  • Animal Models

    female NOD scid gamma (NSG) mice (7-9 weeks old)

  • Dosages

    400 μg/mouse

  • Administration

    SC

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.