Galectin-1 is a member of a family of evolutionarily conserved glycan-binding proteins, displays broad anti-inflammatory and pro-resolving activities by targeting multiple immune cell types[1]. Galectin-1 is also a carbohydrate-binding protein is implicated in cancer cell proliferation, invasion and tumor angiogenesis. OTX008 is a calixarene-based compound and selective galectin-1 (Gal-1) inhibitor with potential anti-angiogenic and antineoplastic activities. OTX008 inhibited tumor cell proliferation, though inhibition was very variable, with IC50 ranging from 1.7 to 192.3 μM. In vivo, the human ovarian carcinoma A2780-1A9 and human glioblastoma U87MG showed a different degree of sensitivity to OTX008 (IC50 of 2.1 and 35.8 μM, respectively). OTX008 achieved a Cmax of 14.39 μg/mL (15.35 μM) and then the drug was rapidly distributed through the body with half-life (HL) of 20 min and cleared from plasma with a long elimination HL of 31.4 h. In vitro, OTX008 inhibited endothelial cell proliferation in a concentration-dependent manner with a mean IC50 values of 9.9 ± 4.2, 8.7 ± 1.7, and 12.9 ± 3.3 μM respectively[2].
OTX008 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CAL-62
30 µM
72 hours
Evaluate the effect of OTX008 on cell proliferation, IC50 was 30 µM
Cells. 2021 May 5;10(5):1112.
TT2609C02
1.1 µM
72 hours
Evaluate the effect of OTX008 on cell proliferation, IC50 was 1.1 µM
Cells. 2021 May 5;10(5):1112.
FTC133
0.3 µM
72 hours
Evaluate the effect of OTX008 on cell proliferation, IC50 was 0.3 µM
Cells. 2021 May 5;10(5):1112.
BCPAP
0.5 µM
72 hours
Evaluate the effect of OTX008 on cell proliferation, IC50 was 0.5 µM
Cells. 2021 May 5;10(5):1112.
TPC-1
0.2 µM
72 hours
Evaluate the effect of OTX008 on cell proliferation, IC50 was 0.2 µM
Cells. 2021 May 5;10(5):1112.
8505c
0.3 µM
72 hours
Evaluate the effect of OTX008 on cell proliferation, IC50 was 0.3 µM
Cells. 2021 May 5;10(5):1112.
SNU449
20 µM
48 hours
To evaluate the effect of OTX008 on the viability of SNU449 cells. Results showed that OTX008 significantly inhibited cell viability at 20 µM concentration.
Mol Oncol. 2022 Mar;16(5):1091-1118.
SNU387
20 µM
48 hours
To evaluate the effect of OTX008 on the viability of SNU387 cells. Results showed that OTX008 significantly inhibited cell viability at 20 µM concentration.
Mol Oncol. 2022 Mar;16(5):1091-1118.
HLE
20 µM
72 hours
To evaluate the effect of OTX008 on the viability of HLE cells. Results showed that OTX008 significantly inhibited cell viability at 20 µM concentration.
Mol Oncol. 2022 Mar;16(5):1091-1118.
PLC/PRF/5
20 µM
72 hours
To evaluate the effect of OTX008 on the viability of PLC/PRF/5 cells. Results showed that OTX008 significantly inhibited cell viability at 20 µM concentration.
Mol Oncol. 2022 Mar;16(5):1091-1118.
MHCC97L
50 μM
OTX008 significantly inhibited the proliferation, migration and invasion of MHCC97L cells
J Exp Clin Cancer Res. 2019 Oct 22;38(1):423.
HL7702 liver cells
10 μmol/L
3 hours
Pretreatment with OTX008 for 3 hours could partially reverse and abolish the DBDCT-associated cytotoxicity, indicating that Gal-1 might be identified as a possible potential target for toxicity and bioactivity.
Bioinorg Chem Appl. 2022 Feb 1;2022:5176300.
H9c2 cells
2.5–1.25–0.75 µM
6 days
Evaluated the effect of OTX008 alone or combined with SBECD on H9c2 cell viability under hyperglycemic conditions, showing no toxicity and significantly improved cell survival.
Pharmaceuticals (Basel). 2024 Jan 12;17(1):107.
ARPE-19 cells
2.5 μM, 5 μM, 10 μM
6 days
OTX008 5 μM and 10 μM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose.
Molecules. 2022 Jul 26;27(15):4785.
OTX008 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
8505c xenograft model
Intraperitoneal injection
5 mg/kg/day
5 days/week for 3 weeks
Evaluate the effect of OTX008 on tumor growth and lung metastasis, results showed significant reduction in tumor volume
Cells. 2021 May 5;10(5):1112.
BALB/c nude mice
Subcutaneous injection and orthotopic implantation model
Intraperitoneal injection
5 mg/3 days
Every 3 days until the end of the experiment
OTX008 alone or in combination with sorafenib significantly inhibited tumor growth and metastasis
J Exp Clin Cancer Res. 2019 Oct 22;38(1):423.
Nude mice
SQ20B and HEp-2 tumor models
Intraperitoneal injection
10 mg/kg
Once daily for 21 days
OTX008 reduced tumor growth by an average of 25% in the SQ20B model, up to 35% on certain days. The effect was less pronounced in the HEp-2 model, whereas Avastin caused tumor growth stabilization.
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