Microtubules are highly dynamic polymers of tubulin that play an important role in mitosis, intracellular transport, and motility. Lexibulin is a synthetic, orally-active tubulin polymerization inhibitor with an IC50 value of ~3μM. It inhibits the proliferation of a panel of cancer cell lines with IC50 values ranging from 10 to 100nM. Treatment of A549 cells with 1μM lexibulin led to rapid destruction of the microtubule network and the accumulation of tubulin in plaques. Incubation of A431 cells with 1μM lexibulin increased the proportion of cells in G2-M at 15 and 24h after the exposure compared to the vehicle-treated group (38% vs. 15%, 43% vs. 19%, respectively). Lexibulin (100nM and 1μM) increased the permeability of human umbilical vein endothelial cell monolayer as early as 1h post-exposure and the IC50 value of lexibulin was ~80nM. In a mouse model of colorectal liver metastases, a single dose of lexibulin (7.5mg/kg, i.p.) significantly decreased blood flow in liver metastases at 6h after treatment[3].
Lexibulin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MG63
0, 20, 40, 80, 160, 320 nM
24 and 48 h
CYT997 significantly inhibits OS cell proliferation and induces apoptosis and autophagy.
J Exp Clin Cancer Res. 2019 Jan 31;38(1):44.
U2OS
0, 20, 40, 80, 160, 320 nM
24 and 48 h
CYT997 significantly inhibits OS cell proliferation and induces apoptosis and autophagy.
J Exp Clin Cancer Res. 2019 Jan 31;38(1):44.
SJSA
0, 20, 40, 80, 160, 320 nM
24 and 48 h
CYT997 significantly inhibits OS cell proliferation and induces apoptosis and autophagy.
J Exp Clin Cancer Res. 2019 Jan 31;38(1):44.
143B
0, 20, 40, 80, 160, 320 nM
24 and 48 h
CYT997 significantly inhibits OS cell proliferation and induces apoptosis and autophagy.
J Exp Clin Cancer Res. 2019 Jan 31;38(1):44.
HeLa S3 cells
50 µM
5 min
Measurement of Lexibulin uptake in ENT1 and ENT2 cells showed that Lexibulin is a nontransported inhibitor of ENT1, and in ENT2 cells, Lexibulin uptake increased in the presence of NBMPR, indicating it is also a nontransported inhibitor of ENT2
Mol Pharmacol. 2021 Feb;99(2):147-162.
Lexibulin 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c-nu mice
143B osteosarcoma xenograft model
Intraperitoneal injection
15 mg/kg
Once daily for 28 days
CYT997 significantly inhibits tumor growth, and the combination with 3-MA enhances the anti-tumor effect.
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