LY2510924

Catalog No.S8505 Batch:S850501

Technical Data

Formula	C₆₂H₈₈N₁₄O₁₀
Molecular Weight	1189.45	CAS No.	1088715-84-7
Solubility (25°C)*	In vitro	Water	100 mg/mL (84.07 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

LY2510924 is a potent and selective CXCR4 antagonist that specifically blocks SDF-1 binding to CXCR4 with IC50 value of 0.079 nmol/L and inhibits SDF-1-induced GTP binding with Kb value of 0.38 nmol/L.

Targets

CXCR4 ^[1]
(Cell-free)

0.079 nM

In vitro

In human lymphoma U937 cells expressing endogenous CXCR4, LY2510924 inhibits SDF-1-induced cell migration with IC50 value of 0.26 nmol/L and inhibits SDF-1/CXCR4-mediated intracellular signaling. LY2510924 exhibits a concentration-dependent inhibition of SDF-1-stimulated phospho-ERK and phospho-Akt in tumor cells. Biochemical and cellular analyses reveal that LY2510924 has no apparent agonist activity. LY2510924 has no inhibitory activities against other chemokine receptors including CCR1, CCR2, CXCR2, and CXCR3 at the concentrations tested. Similarly, there is no activity observed among serotonin, dopamine, and opioid receptors^[1].

In vivo

LY2510924 has acceptable in vivo stability and a pharmacokinetic profile similar to a typical small-molecular inhibitor in preclinical species. LY2510924 shows dose-dependent inhibition of tumor growth in human xenograft models developed with non-Hodgkin lymphoma, renal cell carcinoma, lung, and colon cancer cells that express functional CXCR4. In MDA-MB-231, a breast cancer metastatic model, LY2510924 inhibits tumor metastasis by blocking migration/homing process of tumor cells to the lung and by inhibiting cell proliferation after tumor cell homing. LY2510924 has a dramatically improved in vivo stability with a half-life of 3 to 5 hours in preclinical species and 9.16 hours in humans at the recommended phase II dose^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines U937 cells Concentrations -- Incubation Time 2.5 h Method U937 cells are 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 are then resuspended in assay buffer at a density of 5 × 10⁶ cells/mL. The assay is performed in a 96-well ChemoTx plate. 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 is then incubated for 2.5 hours at 37°C. Following the incubation, 5 μL of CellTiter 96 AQ is added into the lower chamber. The plate is then incubated for 60 minutes at 37°C. The migrated cells are detected by measuring the absorbance at 492 nm.
Animal Study:^{^[1]}	Animal Models female C57/BL6 mice, male Sprague–Dawley rats, male Beagle dogs, and male Cynomolgus monkeys at fasted state Dosages 3 mg/kg Administration subcutaneous (s.c.) or intravenous (i.v.) injection

Cell Assay:^{^[1]}

Cell lines
U937 cells
Concentrations
--
Incubation Time
2.5 h
Method
U937 cells are 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 are then resuspended in assay buffer at a density of 5 × 10⁶ cells/mL. The assay is performed in a 96-well ChemoTx plate. 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 is then incubated for 2.5 hours at 37°C. Following the incubation, 5 μL of CellTiter 96 AQ is added into the lower chamber. The plate is then incubated for 60 minutes at 37°C. The migrated cells are detected by measuring the absorbance at 492 nm.

Animal Study:^{^[1]}

Animal Models
female C57/BL6 mice, male Sprague–Dawley rats, male Beagle dogs, and male Cynomolgus monkeys at fasted state
Dosages
3 mg/kg
Administration
subcutaneous (s.c.) or intravenous (i.v.) injection

References

[1] Peng SB, et al. Mol Cancer Ther. 2015, 14(2):480-90.

Selleck's LY2510924 has been cited by 2 publications

Modeling the SDF-1/CXCR4 protein using advanced artificial intelligence and antagonist screening for Japanese anchovy [ Front Physiol, 2024, 15:1349119]	PubMed: 38370015
Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche [ Nat Commun, 2023, 14(1):2207]	PubMed: 37072407

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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.