The glucose transporter GLUT1 is overexpressed in various types of human cancers. BAY-876 is a highly selective GLUT1 inhibitor with an IC50 value of 2 nM. The IC50 values of BAY-876 for GLUT2, 3, and 4 are 10.8, 1.67, and 0.29 µM[2]. The treatment with BAY-876 (25 – 75 nM) decreased glycolytic rates in SKOV-3, OVCAR-3, and HEY cells in a dose-dependent manner. BAY-876 at doses of 75 nM reduced basal and CoCl2-stimulated glycolysis in SKOV-3, OVCAR-3, and HEY cells. Incubation of SKOV-3 and OVCAR-3 cells with 75 nM BAY-876 caused a significant decrease in cellular ATP level. BAY-876 also inhibited the mitochondrial activity of viable cells with IC50 values of 60, 188, and 1002 nM for OVCAR-3, SKOV-3, and HEY cells, respectively. In female NSG mice carrying SKOV-3 xenografts, the administration of BAY-876 (1.5 - 4.5 mg/kg/day) for 4 weeks does-dependently inhibited tumor growth as compared to the group received no BAY-876 treatment[3].
BAY-876 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HC11 cells
100 nM
24 hours
No obvious negative impact on GLUT1-normal cell populations
Nat Commun. 2023 Nov 2;14(1):7021.
Pt2377
25-400 nM
5 days
BAY-876 inhibited the proliferation of Pt2377 cells.
Mol Cancer Ther. 2022 May 4;21(5):740-750.
LS174T
25-400 nM
5 days
BAY-876 inhibited the proliferation of LS174T cells.
Mol Cancer Ther. 2022 May 4;21(5):740-750.
MDA-MB-468
3 µM
72 hours
No significant changes in cell cycle observed
Nat Commun. 2020 Aug 21;11(1):4205.
MDA-MB-436
3 µM
72 hours
No significant changes in cell cycle observed
Nat Commun. 2020 Aug 21;11(1):4205.
DU145 cells
25 µM, 12 µM, 6 µM, 3 µM, 1.5 µM, 0.7 µM
0, 24, 48, 72 hours
To evaluate the inhibitory effect of BAY-876 on the viability of prostate cancer cells. Results showed that as the concentration of BAY-876 increased, cell activity gradually weakened. The IC50 of PC-3 at 24 h was 0.70 µM, and that of DU145 was 2.19 µM.
Biol Direct. 2024 Oct 23;19(1):97.
PC-3 cells
25 µM, 12 µM, 6 µM, 3 µM, 1.5 µM, 0.7 µM
0, 24, 48, 72 hours
To evaluate the inhibitory effect of BAY-876 on the viability of prostate cancer cells. Results showed that as the concentration of BAY-876 increased, cell activity gradually weakened. The IC50 of PC-3 at 24 h was 0.70 µM, and that of DU145 was 2.19 µM.
Biol Direct. 2024 Oct 23;19(1):97.
HaCaT cells
1 mM
2 hours
To evaluate the inhibitory effect of BAY-876 on Glu-4-ZnPc uptake in HaCaT cells
Pharmaceutics. 2024 Jun 20;16(6):838.
Primary Gingival Keratinocytes
10 nM to 100 µM
24 hours
BAY-876 inhibited glucose uptake in primary gingival keratinocytes and reduced cell viability.
Cell Death Discov. 2024 Jul 25;10(1):339.
FaDu
10 nM to 100 µM
24 hours
BAY-876 inhibited glucose uptake in FaDu cells, reduced cell viability and metabolism, and induced apoptosis.
Cell Death Discov. 2024 Jul 25;10(1):339.
RPMI2650
10 nM to 100 µM
24 hours
BAY-876 inhibited glucose uptake in RPMI2650 cells, reduced cell viability and metabolism, and induced apoptosis.
Cell Death Discov. 2024 Jul 25;10(1):339.
SCC47
10 nM to 100 µM
24 hours
BAY-876 inhibited glucose uptake in SCC47 cells, reduced cell viability and metabolism, and induced apoptosis.
Cell Death Discov. 2024 Jul 25;10(1):339.
4T1 cells
100 nM
24 hours
Inhibited glycolysis activity in 4T1 cells, reduced PD-L1 glycosylation levels, and enhanced the binding affinity of aptPD-L1 to PD-L1
Nat Commun. 2023 Nov 2;14(1):7021.
HCT116 cells
1 µM
24 hours
BAY-876 inhibited the proliferation of HCT116 cells with an IC50 of 0.1–0.2 µmol/L.
Cancers (Basel). 2024 Apr 2;16(7):1399.
LS174T cells
1 µM
24 hours
BAY-876 inhibited the proliferation of LS174T cells with an IC50 of 0.1–0.2 µmol/L.
Cancers (Basel). 2024 Apr 2;16(7):1399.
HEK293 cells
0.05 µM, 1 µM, 5 µM
30 minutes
To assess the inhibitory effect of BAY-876 on glucose uptake mediated by GLUT1-6 and GLUT10. Results showed BAY-876 inhibited glucose uptake via GLUT1, GLUT3, GLUT4, GLUT6, and GLUT10, but not GLUT2.
Biomolecules. 2022 Nov 23;12(12):1734.
HEK293 cells
0.05 µM, 1 µM, 5 µM
30 minutes
To assess the ability of BAY-876 to inhibit hexose uptake via facilitative glucose transporters. Results showed BAY-876 inhibited glucose uptake via GLUT1, GLUT3, GLUT4, GLUT6, and GLUT10, but not GLUT2.
Biomolecules. 2022 Nov 23;12(12):1734.
HepG2 cells
1 µM
48 hours
BAY-876 significantly inhibited the expression of glycogenesis-related genes GBE1, GYS1, UGP2, and glycogenolysis-related gene PYGM
Cancer Metab. 2023 Jul 13;11(1):9.
Huh7 cells
1 µM
48 hours
BAY-876 significantly inhibited the expression of glycogenesis-related genes GBE1, GYS1, UGP2, and glycogenolysis-related gene PYGM
Cancer Metab. 2023 Jul 13;11(1):9.
Hs 578T
3 µM
72 hours
Inhibited cell growth and proliferation, increased cell cycle arrest and apoptosis
Nat Commun. 2020 Aug 21;11(1):4205.
HCC1806
3 µM
72 hours
Inhibited cell growth and proliferation, increased cell cycle arrest and apoptosis
Nat Commun. 2020 Aug 21;11(1):4205.
GL261 cells
2 nM
72 hours
Inhibit GLUT1 expression and reduce lactate excretion
Adv Sci (Weinh). 2024 May;11(18):e2310163.
UMRC6 cells
2 µM
Measure cell death, results showed BAY-876 significantly increased death in SLC7A11-high cells
Nat Cell Biol. 2020 Apr;22(4):476-486.
786-O cells
2 µM
Measure glucose uptake levels and NADP+/NADPH ratios, results showed BAY-876 significantly inhibited glucose uptake and increased NADP+/NADPH ratios
Nat Cell Biol. 2020 Apr;22(4):476-486.
BAY-876 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Balb/c mice
4T1 tumor model
Intravenous injection
0.05 µg/mL/g
Once every two days for 21 days
Significantly inhibited tumor growth, reduced lactic acid and UDP-GlcNAc levels in the tumor microenvironment, and enhanced anti-tumor immune responses
Nat Commun. 2023 Nov 2;14(1):7021.
Mice
Muscle-specific GLUT1 knockout mice
In vitro muscle incubation
0.05 μM, 1 μM, 5 μM
60 minutes
To evaluate the effect of BAY-876 on basal and overload-stimulated muscle glucose uptake. Results showed that low-dose BAY-876 (0.05 μM) completely impaired overload-stimulated glucose uptake but did not affect basal uptake.
Biomolecules. 2022 Nov 23;12(12):1734.
Mice
Muscle-specific GLUT1 knockout (mGLUT1KO) mice
Ex vivo muscle incubation
0.05 μM, 1 μM, 5 μM
60 minutes
To assess the effect of BAY-876 on basal and overload-stimulated muscle glucose uptake. Results showed that a low dose of BAY-876 (0.05 μM) completely impaired overload-stimulated but not basal glucose uptake.
Biomolecules. 2022 Nov 23;12(12):1734.
C57BL/6 mice
STZ-induced hyperglycemic model
Intravenous injection
1.0 mg/kg
Daily injections for 16 days
BAY-876 significantly reduced STZ-induced astrocyte proliferation but had no effect on microglia numbers
J Neuroinflammation. 2024 May 27;21(1):137
Balb/c mice
4T1 breast tumor xenograft model
Tail vein injection
10 mg/kg
Single dose, monitored for 14 days
Evaluate the in vivo antitumor efficacy and biodistribution of CFMB, showing significant tumor growth suppression without systemic toxicity.
Adv Sci (Weinh). 2024 Jun;11(23):e2401738
Mice
NCI-H226 xenograft tumors
Intraperitoneal injection
100 mg/kg
Every two days
Evaluate the therapeutic effect of GLUT inhibitors on SLC7A11-high tumors, results showed BAY-876 significantly suppressed tumor growth
Nat Cell Biol. 2020 Apr;22(4):476-486.
Mice
PDX model
Oral
2 mg/kg daily
Once daily for 30 days
Impaired tumor growth with no significant loss of body weight
Nat Commun. 2020 Aug 21;11(1):4205.
C57BL/6J mice
Subcutaneous GBM model
Subcutaneous injection
2 nM
21 days
Inhibit lactate excretion and delay tumor growth
Adv Sci (Weinh). 2024 May;11(18):e2310163.
Nude mice
HCC xenograft model
Gavage
2.5 mg/kg
Every 3 days for 28 days
BAY-876 significantly inhibited BMP4-induced subcutaneous tumor growth and glycogen accumulation
Cancer Metab. 2023 Jul 13;11(1):9.
RAG1−/−γc− mice
LS174T cell xenograft model
Oral administration
3 mg/kg/day
Once daily for 12 days
BAY-876 significantly inhibited tumor growth in the LS174T cell xenograft model.
Cancers (Basel). 2024 Apr 2;16(7):1399.
SCID mice
LS174T xenograft model
Oral (BAY-876), Intraperitoneal (DBI-1)
3 mg/kg/day (BAY-876), 40 mg/kg/day (DBI-1)
Once daily for 12 days
BAY-876 and DBI-1 alone or in combination inhibited tumor growth, with combination therapy being more effective than either compound alone.
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