ZK756326 2HCl

Catalog No.S8324 Batch:S832401

Technical Data

Formula	C₂₁H₂₈N₂O₃.2HCl
Molecular Weight	429.38	CAS No.	874911-96-3
Solubility (25°C)*	In vitro	Water	78 mg/mL (181.65 mM)
		DMSO	39 mg/mL (90.82 mM)
		Ethanol	4 mg/mL (9.31 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.)

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Biological Activity

Description

ZK756326 is a full agonist of CCR8（Chemokine receptor 8） with an IC50 of 1.8 μM, dose-responsively eliciting an increase in intracellular calcium and cross-desensitizing the response of the receptor to CCL1.

Targets

CCR8 ^[1]
(in U87 cell line)

1.8 μM

In vitro

ZK 756326 stimulated extracellular acidification in cells expressing human CCR8. The ability of ZK 756326 to induce a response was receptor-specific and mediated through Gαi, because it could be blocked by treatment with pertussis toxin. Like CCL1, ZK 756326 inhibited human immunodeficiency virus (HIV) fusion of cells expressing CD4 and CCR8. But unlike mCCL1, ZK 756326 bound to and activated a form of mCCR8 that was mutated to eliminate O-linked sulfation at tyrosines 14 and 15. Therefore, ZK 756326 is most probably not binding in the same manner as CCL1 but can activate the switch mechanism involved in transducing signaling events^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines BW5147.3 cells Concentrations 10, 60, 400, 2400 nM Incubation Time 2 h Method Cells are resuspended in RPMI with 1% (w/v) BSA and 25 mM HEPES, pH 7.4 (3 × 10⁵ cells/well), and 100-μl aliquots were loaded into upper inserts. Samples of mCCL1 and ZK 756326 prepared in 600 μl of the same medium were placed in the lower wells. After incubation (2 h at 37°C), inserts were removed, and the migrated cells were counted in an EPICS XL flow cytometer. Duplicate wells were used for each point. A migration index was established as the ratio of the number of cells that had migrated in response to the chemokine or to ZK 756326 divided by the number of cells that had migrated in response to buffer alone.

Cell Assay:^{^[1]}

Cell lines
BW5147.3 cells
Concentrations
10, 60, 400, 2400 nM
Incubation Time
2 h
Method
Cells are resuspended in RPMI with 1% (w/v) BSA and 25 mM HEPES, pH 7.4 (3 × 10⁵ cells/well), and 100-μl aliquots were loaded into upper inserts. Samples of mCCL1 and ZK 756326 prepared in 600 μl of the same medium were placed in the lower wells. After incubation (2 h at 37°C), inserts were removed, and the migrated cells were counted in an EPICS XL flow cytometer. Duplicate wells were used for each point. A migration index was established as the ratio of the number of cells that had migrated in response to the chemokine or to ZK 756326 divided by the number of cells that had migrated in response to buffer alone.

References

[1] Haskell Ca, et al. Mol Pharmacol. 2006, 69(1):309-16.

Selleck's ZK756326 2HCl has been cited by 2 publications

Tumor-derived exosomes drive pre-metastatic niche formation in lung via modulating CCL1+ fibroblast and CCR8+ Treg cell interactions [ Cancer Immunol Immunother, 2022, 10.1007/s00262-022-03196-3]	PubMed: 35428909
A CCL1/CCR8-dependent feed-forward mechanism drives ILC2 functions in type 2-mediated inflammation. [ J Exp Med, 2019, 216(12):2763-2777]	PubMed: 31537642

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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.

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