WZB117 is a glucose transporter 1 (Glut1) inhibitor, which downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo[1]. WZB117 impedes glucose transport into cancer cells in a dose-responsive manner as shown by glucose uptake assays. This blockage occurs rapidly, within 1 minute of assay initiation, indicating a direct and swift mode of action. Cell viability assays demonstrate WZB117's capacity to inhibit cancer cell proliferation with an IC50 value around 10 μM. Clonogenic assays further validate WZB117's suppressive effect on cancer cell growth, suggesting this effect is irreversible. WZB117 treatment leads to more pronounced growth inhibition in lung cancer A549 cells compared to non-tumorigenic NL20 lung cells, with similar trends observed between breast cancer MCF7 cells and non-tumorigenic MCF12A cells. Under hypoxic conditions, cancer cells exhibit increased sensitivity to WZB117 compared to normoxic conditions[1].
体内研究
In animal studies, daily intraperitoneal injections of WZB117 at 10 mg/kg body weight significantly reduce tumor sizes by more than 70% compared to tumors in mock-treated mice. Body weight measurements indicate that WZB117-treated mice experience a weight loss of about 1 to 2 grams, primarily from fat tissue, compared to mock-treated mice[1].
体外研究
WZB117 is a glucose transporter 1 (Glut1) inhibitor, which downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo[1].
WZB117 impedes glucose transport into cancer cells in a dose-responsive manner as shown by glucose uptake assays. This blockage occurs rapidly, within 1 minute of assay initiation, indicating a direct and swift mode of action. Cell viability assays demonstrate WZB117's capacity to inhibit cancer cell proliferation with an IC50 value around 10 μM. Clonogenic assays further validate WZB117's suppressive effect on cancer cell growth, suggesting this effect is irreversible. WZB117 treatment leads to more pronounced growth inhibition in lung cancer A549 cells compared to non-tumorigenic NL20 lung cells, with similar trends observed between breast cancer MCF7 cells and non-tumorigenic MCF12A cells. Under hypoxic conditions, cancer cells exhibit increased sensitivity to WZB117 compared to normoxic conditions[1].
WZB117 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Cortical neurons
10 µM
24 hours
No effect on cell viability
Antioxidants (Basel). 2021 Sep 3;10(9):1413.
CHO cells
3 µM
Validate the inhibitory activity of WZB117 on GluN1/GluN3A receptors
Front Pharmacol. 2022 Jun 9;13:888308.
MCF-7 cells
50 µM
1.5 hours
Evaluate the activity of GLUT1 inhibitors, WZB117 showed significant inhibition of glucose uptake
Molecules. 2022 Nov 21;27(22):8106.
Human erythrocytes
0.1 µM to 7 µM
10 min to 1 min
WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with Ki(app) of 6.2 μM.
J Biol Chem. 2016 Dec 23;291(52):26762-26772.
HEK-293 cells
1.15 ± 0.34 µM (IC50)
20 minutes
Evaluate the inhibitory activity and IC50 value of WZB117 on GluN1/GluN3A receptors
Front Pharmacol. 2022 Jun 9;13:888308.
Peritoneal macrophages
50 and 100 µM
2–3 hours
Evaluate the inhibitory effect of WZB117 on macrophage glycolysis
Evaluate the effect of WZB117 on glycolysis activity and mitochondrial respiration in SW620 cells, showing significant inhibition of glycolysis.
EBioMedicine. 2018 Jul;33:105-121.
SW480 cells
80 µM
24 hours
Evaluate the effect of WZB117 on glycolysis activity and mitochondrial respiration in SW480 cells, showing significant inhibition of glycolysis.
EBioMedicine. 2018 Jul;33:105-121.
HTR8/SVneo cells
20 µM
24 hours
To evaluate the effect of WZB117 on ferroptosis in HTR8/SVneo cells under high glucose conditions. Results showed that WZB117 significantly reduced RSL3-induced ferroptosis, indicating that GLUT1 inhibition can protect trophoblast cells from ferroptosis.
Mol Med. 2024 Dec 20;30(1):257.
Cortical astrocytes
5 µM and 10 µM
24 hours
Significant decrease in viability at 10 µM
Antioxidants (Basel). 2021 Sep 3;10(9):1413.
U87 cells
5 µM and 10 µM
24 hours
No effect on viability at 5 µM, decreased viability by 28.57% at 10 µM
Evaluate the cytotoxicity of WZB117-OCMC-MET on MCF-10A cells, showing an IC50 of 93.3 µg/mL, indicating low toxicity to normal cells.
Polymers (Basel). 2023 Feb 16;15(4):976.
MDA-MB-231
8.3 µg/mL
48 hours
Evaluate the cytotoxicity of WZB117-OCMC-MET on MDA-MB-231 cells, showing an IC50 of 8.3 µg/mL.
Polymers (Basel). 2023 Feb 16;15(4):976.
MCF-7
10.2 µg/mL
48 hours
Evaluate the cytotoxicity of WZB117-OCMC-MET on MCF-7 cells, showing an IC50 of 10.2 µg/mL.
Polymers (Basel). 2023 Feb 16;15(4):976.
A549
50 µM
48 hours
Inhibition of glucose uptake and glycolysis, but with minimal impact on the viability of ADC cell lines
Nat Commun. 2017 May 26;8:15503.
HCC2814
50 µM
48 hours
Inhibition of glucose uptake and glycolysis, significantly reducing the viability of SqCC cell lines
Nat Commun. 2017 May 26;8:15503.
HCC1588
50 µM
48 hours
Inhibition of glucose uptake and glycolysis, significantly reducing the viability of SqCC cell lines
Nat Commun. 2017 May 26;8:15503.
HCC95
50 µM
48 hours
Inhibition of glucose uptake and glycolysis, significantly reducing the viability of SqCC cell lines
Nat Commun. 2017 May 26;8:15503.
SK-MEL-28
113.91 µM
48 hours
To evaluate the inhibitory effect of WZB117 on SK-MEL-28 cell proliferation, results showed that WZB117 inhibited cell proliferation in a dose- and time-dependent manner.
Front Pharmacol. 2022 Sep 16;13:976117.
A375
116.85 µM
48 hours
To evaluate the inhibitory effect of WZB117 on A375 cell proliferation, results showed that WZB117 inhibited cell proliferation in a dose- and time-dependent manner.
Front Pharmacol. 2022 Sep 16;13:976117.
MDA-MB-231 cells
60 µM
48 hours
WZB117 inhibits glucose uptake in MDA-MB-231 cells and shows synergistic growth inhibition and apoptosis induction when combined with MK-2206.
Front Pharmacol. 2019 Nov 6;10:1311.
MCF-7 cells
60 µM
48 hours
WZB117 inhibits glucose uptake in MCF-7 cells and shows synergistic growth inhibition and apoptosis induction when combined with MK-2206.
Front Pharmacol. 2019 Nov 6;10:1311.
GIST-T1/IM-R cells
10 µM
72 hours
WZB117 significantly downregulated AKT phosphorylation and Bcl-2 expression, and combined use with imatinib showed synergistic growth inhibition effects in apoptosis assays.
Oncol Rep. 2022 Jan;47(1):7.
SKOV3 cells
100 µM
90 minutes
Evaluate the activity of GLUT1 inhibitors, WZB117 showed significant inhibition of glucose uptake
Molecules. 2022 Nov 21;27(22):8106.
COS-7 cells
100 µM
90 minutes
Evaluate the activity of GLUT1 inhibitors, WZB117 showed significant inhibition of glucose uptake
Molecules. 2022 Nov 21;27(22):8106.
HEK293 cells
0.1 µM to 13.32 µM
WZB117 inhibits GLUT1- and GLUT3-mediated 2-deoxy-D-glucose (2DG) uptake with Ki(app) of ~10 μM but is a more potent inhibitor of GLUT4-mediated uptake (Ki(app) of 0.2 μM).
J Biol Chem. 2016 Dec 23;291(52):26762-26772.
WZB117 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rat
Postnatal day 5 rats
Cerebral cortex injection
10 µM
Single injection, lasting 72 hours
Inhibited GLUT1, reduced neurite length and branching
Antioxidants (Basel). 2021 Sep 3;10(9):1413.
Nude mice
HCC1588 and HCC2814 xenograft models
Intraperitoneal injection
10 mg/kg
Once daily for 3-4 weeks
GLUT1 inhibition significantly suppressed SqCC tumor growth but had no significant effect on ADC tumor growth
Nat Commun. 2017 May 26;8:15503.
C57BL/6 mice
Orthodontic tooth movement (OTM) model
Intraperitoneal injection
10 mg/kg
Every other day for 7 days
Inhibited GLUT1 activity, reduced orthodontic tooth movement distance and osteoclastic activities.
Int J Oral Sci. 2018 Aug 15;10(3):27.
C57BL/6J mice
STZ-induced gestational diabetes model
Intraperitoneal injection
10 mg/kg
Every other day from E13.5 to E18.5
To evaluate the effect of WZB117 on fetal growth restriction in STZ-induced gestational diabetes mouse model. Results showed that WZB117 treatment significantly improved fetal weight and crown-rump length, reduced placental ferroptosis markers, indicating that GLUT1 inhibition can ameliorate gestational diabetes-associated fetal growth restriction.
Mol Med. 2024 Dec 20;30(1):257.
Nude mice
ICCA patient-derived xenograft (PDX) model
Intraperitoneal injection
10 mg/kg
Once daily for 6 weeks
WZB117 inhibited the tumor growth of the PDX#4 models but did not inhibit tumor growth in the PDX#1 group.
Oncogenesis. 2020 Feb 13;9(2):19
Sprague-Dawley (SD) rats
TMJ degeneration model
Intra-articular injection
10 mg/ml
Daily for the duration of the experiment
Inhibited GLUT1 expression, reducing chondrocyte hypertrophy and O-GlcNAcylation levels
Bone Joint Res. 2025 Mar 10;14(3):209-222.
Mice
Orthotopic model of pancreatic ductal adenocarcinoma
Oral
250 ppm (equivalent to a 50 mg/kg daily dose)
Once daily for 7 days
Evaluate the effect of WZB117 on tumor burden, results showed WZB117 significantly reduced tumor burden
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