Through binding with CC- and CXC-chemokines, CCR and CXCR, the subsets of the chemokine receptor family can trigger an intracellular signal transduction cascade, thus mediating the recruitment of immune cells to the inflammation or infection sites and implicated in several immuno-related disease states, organogenesis, angiogenesis and tumor growth and metastasis. WZ811 is a potent and selective CXCR4 inhibitor with subnanomolar EC50 value of 0.3nM. Pre-treatment with WZ811 for 15min dose-dependently caused reduction of SDF-1 (150ng/ml)-induced cAMP level with EC50 of 1.2nM (measured by TR-FRET based LANCE assay kit). The inhibition of SDF-1 induced matrigel invasion by WZ811 can also be observed with EC50 of 5.2nM[1]. Treatment with WZ811 for 48h at dose ranging in 5-40μM significantly inhibited proliferation of chronic lymphocytic leukemia cells, TF-1 and UT-7, as well as induced apoptosis at dose of 5μM for 24h. Daily oral dose with WZ811 (40mg/kg) for 25days suppressed the lymphocytic leukemia cells growth on mouse xenograft models[2].
作用机制
WZ811 can inhibit CXCR4 through the competition binding.[1]
WZ811 细胞实验
Cell Line
Concentration
Treated Time
Description
References
M-07e
1 µM
12 hours
WZ811 significantly decreased the migration number of M-07e induced by BLM-treated lung tissues.
Cell Death Dis. 2019 Sep 9;10(9):648.
Medullary thyroid carcinoma cell line TT
100 nM and 1 µM
24 hours
To investigate the effect of WZ811 on the invasiveness of medullary thyroid carcinoma cells, the results showed that WZ811 significantly reduced the invasiveness of cancer cells.
Br J Cancer. 2017 Dec 5;117(12):1837-1845.
Human follicular thyroid carcinoma cell line TT2609-C02
1 µM and 100 nM
24 hours
Investigate the effect of WZ811 on the invasiveness of TT2609-C02 cells, results showed WZ811 significantly reduced the number of invading cells
J Cancer. 2018 Feb 27;9(6):929-940.
MELHO cells
10 µM
WZ811 inhibited CXCR4, reduced osteotropism, and activated mTOR and p70-S6 cell signaling proteins.
Cells. 2024 Feb 27;13(5):408.
1F5 RUNX2 KO cells
1.3 µg/mL and 2.6 µg/mL
Restored RUNX2 expression increased the levels of CXCR4 and proteins associated with the metastatic process.
Cells. 2024 Feb 27;13(5):408.
WZ811 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
BLM-induced pulmonary fibrosis model
Intragastric administration
4 mg/kg
Once daily for 14 consecutive days
WZ811 significantly attenuated BLM-induced pulmonary fibrosis, reduced the migration of CD41+ megakaryocytes, and decreased collagen deposition and TGF-β1 levels in lung tissue.
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