O-GlcNAcylation is an important posttranslational modification governed by a single pair of enzymes-O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). These two enzymes mediate the dynamic cycling of O-GlcNAcylation on a wide variety of cytosolic, nuclear and mitochondrial proteins in a nutrient- and stress-responsive fashion[1]. OGT catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial proteins, including numerous transcription factors, tumour suppressors, kinases, phosphatases and histone-modifying proteins[2].Biofunctional investigation demonstrated that OGT significantly increased cell growth (p<0.001), clonogenicity (p<0.01), migration and invasion (p<0.05) ability in vitro, and promoted xenograft tumor growth as well as lung metastasis in nude mice[3].OSMI-1 is a cell-permeable OGT inhibitor with an IC50 value of 2.7 μM. OSMI-1 inhibits protein O-linked N-acetylglucosamine (O-GlcNAcylation) in several mammalian cell lines without qualitatively altering cell surface N- or O-linked glycans. OSMI-1 (50 μM; 24 hours; CHO cells) treatment decreases the viability by about 50% after 24 hours. OSMI-1 (10-100 μM; 24 hours; CHO cells) treatment reduces global O-linked N-acetylglucosamine (O-GlcNAcylation) a dose-dependent manner. OSMI-1 inhibits OGT activity in cells[4].Mammalian and zebrafish toxicity profiles are strikingly similar, and zebrafish can usually serve as an intermediate step between cell-based evaluation and conventional animal testing. The zebrafish model is used to investigate OSM1-1 acute toxicity in vivo. The LC50 of OSM1-1 is 0.031 mg/mL (56 μM, 12 h) and 0.025 mg/mL (45 μM, 24 h) in zebrafish model[5].
OSMI-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Huh7-HBV1.3 cells
20 µM
12 hours
Inhibited YTHDF2 O-GlcNAcylation and downregulated MCM2 and MCM5 mRNA levels
Signal Transduct Target Ther. 2023 Feb 10;8(1):63.
HepG2-HBV1.3 cells
20 µM
12 hours
Inhibited YTHDF2 O-GlcNAcylation and downregulated MCM2 and MCM5 mRNA levels
Signal Transduct Target Ther. 2023 Feb 10;8(1):63.
Neuroblastoma N2a cells
60 µM
12 hours
Inhibited O-GlcNAc levels, significantly impaired cell viability, and accelerated apoptosis
Acta Pharmacol Sin. 2024 Apr;45(4):714-727.
AML12 cells
20 µM
15 hours
To evaluate the effect of OSMI-1 on normal hepatocytes, results showed no significant impact on apoptosis in AML12 cells.
Cancers (Basel). 2020 Oct 27;12(11):3154.
HepG2 cells
20 µM
15 hours
To evaluate the effect of OSMI-1 on apoptosis in HepG2 cells, results showed OSMI-1 significantly enhanced DOX-induced apoptosis.
Cancers (Basel). 2020 Oct 27;12(11):3154.
NK92 cells
25 µM
24 hours
OSMI-1 treatment led to decreased expression of NKG2D and NKG2A, increased expression of KIR2DL1, and significantly reduced cytotoxicity in NK92 cells.
Front Immunol. 2022 Apr 11;13:841299.
Primary NK cells
25 µM
24 hours
Inhibition of O-GlcNAcylation resulted in decreased expression of NK cell receptors (NKG2D, NKG2A, NKp44), cytokines (TNF-α, IFN-γ), granulysin, soluble Fas ligand, perforin, and granzyme B in NK cells, leading to reduced cytotoxic function.
Front Immunol. 2022 Apr 11;13:841299.
HepG2 cells
20 µM
24 hours
The combination treatment of OSMI-1 and TRAIL significantly increased the apoptosis rate in HepG2 cells.
Int J Mol Sci. 2021 Oct 14;22(20):11073.
HCT116 human colon cancer cells
20 µM
24 hours
OSMI-1 significantly increased TRAIL-mediated apoptosis by increasing the expression of the cell surface receptor DR5. ROS-induced ER stress by OSMI-1 not only upregulated CHOP-DR5 signaling but also activated JNK, resulting in a decrease in Bcl2 and the release of cytochrome c from mitochondria.
Int J Mol Sci. 2021 Oct 14;22(20):11073.
IPAH PAECs:PASMCs
25 µM
24 hours
To assess the effect of OGT inhibition on vascular sprouting in a 3D co-culture model, results showed that OSMI-1 reduced sprouts and sprout length in IPAH spheroids.
Int J Mol Sci. 2019 Dec 13;20(24):6299.
IPAH PAECs
25 µM
24 hours
To assess the effect of OGT inhibition on SP1 O-GlcNAc modification, results showed that OSMI-1 reduced O-GlcNAc modification levels on SP1 in IPAH PAECs.
Int J Mol Sci. 2019 Dec 13;20(24):6299.
Non-IPF lung fibroblasts
25 µM
24 hours
To examine the blocking effect of OSMI-1 on TGF-β1-induced downregulation of Cox2 and Hmox1. Results showed that pretreatment with OSMI-1 attenuated the inhibitory effects of TGF-β1 on Cox2 and Hmox1.
J Cell Mol Med. 2024 Apr;28(7):e18191.
Primary IPF lung fibroblasts
25 µM
24 hours
To investigate the effects of OSMI-1 on the expression of Cox2 and Hmox1. Results showed that Cox2 and Hmox1 expression at both mRNA and protein levels were significantly increased following OGT inhibition.
J Cell Mol Med. 2024 Apr;28(7):e18191.
Chondrocytes
20 µM
3 days
Inhibiting O-GlcNAcylation, partially mitigating compression-induced hypertrophic differentiation of chondrocytes
Bone Joint Res. 2025 Mar 10;14(3):209-222.
Human iPSC-derived cardiomyocytes
50 µM
30 minutes
Inhibition of GlcNAcylation, prevented Hi-Glu-induced ROS production
Circ Res. 2020 May 8;126(10):e80-e96.
Adult mouse ventricular myocytes
50 µM
30 minutes
Inhibition of GlcNAcylation, prevented ROS induction in response to either Hi-Glu or Thm-G
Circ Res. 2020 May 8;126(10):e80-e96.
Bone marrow-derived macrophages (BMMs)
5 µM
4 days
OSMI-1 dose-dependently reduced the number of TRAP-positive mature osteoclasts and actin belt formation, and decreased the overall O-GlcNAcylation level with a significant and concomitant decline in NFATc1 levels during osteoclast differentiation.
Int J Mol Sci. 2021 Aug 18;22(16):8888.
HCT116 cells
5, 10, 20 µM
48 hours
OSMI-1 significantly increased the expression of LC3-II and the ratio of LC3-II/LC3-I, indicating an increase in autophagic flux.
Cancer Cell Int. 2023 Jun 2;23(1):108.
RLE-6TN cells
1 µM
48 hours
To evaluate the effect of OSMI-1 on the proliferation of hyperoxia-induced RLE-6TN cells. Results showed that OSMI-1 treatment for 48 h increased cell proliferation by 41.1%.
Respir Res. 2023 Jan 16;24(1):16.
Human monocyte derived dendritic cells (moDCs)
20 µM
6 days
Investigated the effects of OGT inhibitor OSMI-1 on the differentiation and maturation process of moDCs, showing modulation of AKT and MEK/ERK pathways, altered expression of surface markers, and cytokine secretion.
Cells. 2021 Nov 26;10(12):3312.
HCT116 cells
10 µM
6 hours
To study the effect of OSMI-1 on OGT intron retention, results showed that OSMI-1 treatment increased OGT mRNA levels.
Cell Rep. 2017 Aug 1;20(5):1088-1099.
293A-TOA cells
10 µM
6 hours
To study the effect of OSMI-1 on OGT intron retention, results showed that OSMI-1 treatment increased the efficiency of β-OGT splicing.
Cell Rep. 2017 Aug 1;20(5):1088-1099.
IPAH PAECs
25 µM
6 hours
To assess the effect of OGT inhibition on endothelial tube formation, results showed that OSMI-1 significantly reduced the number of tube-like structures and tube length in IPAH PAECs.
Int J Mol Sci. 2019 Dec 13;20(24):6299.
HEK293 cells
25 µM
6 hours
Metabolic labeling and pull-down assays confirmed that OSMI-1 treatment prevented O-GlcNAcylation of p38.
J Biol Chem. 2023 Mar;299(3):102907.
Neonatal rat ventricular myocytes (NRVMs)
25 µM
6 hours
Inhibited OGT activity, reduced protein O-GlcNAcylation by 50%, and induced a 3.9-fold increase in p38 phosphorylation.
J Biol Chem. 2023 Mar;299(3):102907.
LNCaP-AI cells
20 µM
72 hours
OSMI-1 significantly inhibited the proliferation of LNCaP-AI cells.
Cell Death Dis. 2024 Nov 6;15(11):796.
OSMI-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
LNCaP-AI xenograft model
Intravenous injection
1 mg/kg
Administered every other day for 4 weeks
OSMI-1 significantly inhibited the growth of LNCaP-AI xenograft tumors.
Cell Death Dis. 2024 Nov 6;15(11):796.
Nude mice
HCT116 xenograft model
Intravenous injection
1 mg/kg
Once daily for 21 days
The combination treatment of OSMI-1 and TRAIL significantly reduced tumor volume and weight by enhancing ER stress response and inhibiting NF-κB signaling.
Int J Mol Sci. 2021 Oct 14;22(20):11073.
Nude mice
HepG2 xenograft model
Intravenous injection
1 mg/kg (OSMI-1) and 0.1 mg/kg (DOX)
Once every 3 days for 3 weeks
To evaluate the effect of combination therapy with OSMI-1 and DOX on tumor growth, results showed significant inhibition of tumor growth.
Cancers (Basel). 2020 Oct 27;12(11):3154.
BALB/c nude mice
HCT116 xenograft model
Intravenous injection
1 mg/kg/day
Once daily for 28 days
Combination treatment significantly inhibited the growth of HCT116 xenograft tumors, with a significant reduction in tumor volume and weight.
Cancer Cell Int. 2023 Jun 2;23(1):108.
C57BL/6 male mice
LPS-induced bone loss model
Subcutaneous injection
10 mg/kg/day
Once daily for 6 days
OSMI-1 significantly reduced the number of TRAP-specific mature osteoclasts in the calvarial surfaces and sections.
Int J Mol Sci. 2021 Aug 18;22(16):8888.
Sprague Dawley rats
Hyperoxia-induced neonatal rat model of bronchopulmonary dysplasia
Intraperitoneal injection
10 mg/kg/day
Once daily for 14 days
To evaluate the effect of OSMI-1 on hyperoxia-induced alveolarization in neonatal rats. Results showed that OSMI-1 promoted alveolarization and increased RAC values.
Respir Res. 2023 Jan 16;24(1):16.
Sprague-Dawley (SD) rats
Temporomandibular joint (TMJ) degeneration model
Intra-articular injection
10 mg/ml
Once daily for the duration of the experiment
Inhibiting O-GlcNAcylation, mitigating FMR-induced hypertrophic differentiation of chondrocytes
Bone Joint Res. 2025 Mar 10;14(3):209-222.
Mice
REM sleep deprivation model
Intraperitoneal injection
100 µg/kg
Single dose, lasting 2 hours
OSMI-1 inhibited OGT activity, resulting in impaired memory function and inhibition of FC-induced PKA/CREB activation.
Neurotherapeutics. 2021 Oct;18(4):2504-2517
Mice
Xenograft tumor model
Intraperitoneal injection
20 mg/kg
Once daily for 24 days
To study the tumor growth of ISS-deleted cells under OGA inhibition, results showed that tumor growth of ISS-deleted cells was compromised.
Cell Rep. 2017 Aug 1;20(5):1088-1099.
NOD/SCID mice
Humanized angiogenic mouse model
Collagen implants
25 µM
Single administration, lasting 7-14 days
To assess the effect of OGT inhibition on in vivo vascularization, results showed that OSMI-1 reduced vascularization in IPAH PAECs.
Int J Mol Sci. 2019 Dec 13;20(24):6299.
HBV-transgenic mice
DEN/CCl4-induced HCC model
Intraperitoneal injection
5 mg/kg
Twice a week for 12 weeks
Inhibited YTHDF2 O-GlcNAcylation and decelerated liver tumorigenesis
Signal Transduct Target Ther. 2023 Feb 10;8(1):63.
Mice
Stx2a intoxication model
Injection
Daily injection
Daily administration starting from the day before intoxication
OSMI-1 significantly protected mice from weight loss, elevated kidney injury markers, and death
2022 Jan 11;14(1):e15389. doi: 10.15252/emmm.202115389
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