T0070907 is a potent and selective PPARγ antagonist with Ki value of 1nM, with >800-fold preference for PPARγ over PPARα and PPARδ with Ki values of 0.85μM and 1.8 μM. T0070907 at concentration ranging in 1nM-1μM dose-dependently antagonized the effects of rosiglitazone at concentration 1μM in HTRF assays, blocking agonist-induced recruitment of coactivator-derived peptides to PPARγ. It promoted recruitment of the transcriptional corepressor NCoR to PPARγ/RXR heterodimer[1]. Treatment with 50μM T0070907 for 24h led loss of 70% cell adherence in trypsinized HepG2 cells, associated with reductions in phosphorylated FAK[2].
作用机制
T0070907 covalently modifies PPARγ on cysteine 313 in helix 3 of human PPARγ2. T0070907 modulates the interaction of PPARγ with cofactor proteins by affecting the conformation of helix 12 of the PPARγ ligand-binding domain.[1]
T0070907 细胞实验
Cell Line
Concentration
Treated Time
Description
References
WM4265.2-BrM1 cells
10μM
48 h
PPARγ antagonist inhibited the growth of WM4265.2-BrM1 cells
Cancer Discov. 2019 Dec;9(12):1720-1735.
MDA231-BrM cells
10μM
48 h
PPARγ antagonist inhibited the proliferation of MDA231-BrM cells
Cancer Discov. 2019 Dec;9(12):1720-1735.
BV2 cells
10 μM
20 h
To detect the effect of T0070907 on the anti-inflammatory effects of VCE-003.2, the results showed that T0070907 did not inhibit the inhibitory effects of VCE-003.2 on TNF-α, IL-1β, COX-2, and iNOS
J Neuroinflammation. 2018 Jan 16;15(1):19.
M-213 cells
10 μM
40 h
To detect the effect of T0070907 on the neuroprotective effects of VCE-003.2, the results showed that T0070907 did not inhibit the protective effect of VCE-003.2 on M-213 cells.
J Neuroinflammation. 2018 Jan 16;15(1):19.
ILC2s
2 µM
48 h
To investigate the effect of T0070907 on cytokine secretion in ILC2s, results showed that T0070907 significantly reduced IL-13 secretion.
Nat Commun. 2021 May 5;12(1):2538.
Th17 cells
2 μM
3 days
To study the effect of T0070907 on Th17 cell polarization, results showed that T0070907 inhibited Th17 cell polarization.
Nat Immunol. 2022 Jul;23(7):1063-1075.
HPAC cells
5 or 10 μM
72 h
T0070907 inhibited the transcriptional activity of PPARγ and suppressed the proliferation and colony-formation capacity of HPAC and SW1990 cells.
Front Cell Dev Biol. 2022 Feb 2;9:745554.
SW1990 cells
5 or 10 μM
72 h
T0070907 inhibited the transcriptional activity of PPARγ and suppressed the proliferation and colony-formation capacity of HPAC and SW1990 cells.
Front Cell Dev Biol. 2022 Feb 2;9:745554.
PANC-1 cells
5 or 10 μM
72 h
T0070907 inhibited cell proliferation in PANC-1 cells but had no effect on cell growth and body weight in vivo.
Front Cell Dev Biol. 2022 Feb 2;9:745554.
T0070907 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c mice
Acute or chronic chemotherapy-induced neuropathic pain model
Intraperitoneal injection
30 mg/kg
Once daily for 5 consecutive days
ELB00824 significantly reduced oxaliplatin-induced cold hyperalgesia and mechanical allodynia and oxidative stress.
Neuropharmacology. 2022 Nov 1;218:109233.
Mice
High-fat diet-induced obesity model
Intraperitoneal injection
2 mg/kg
Single dose, lasting 1 day
To verify whether PRMT4-mediated white adipose tissue browning is dependent on PPARγ, the results showed that T0070907 inhibited PRMT4-induced thermogenic gene expression and cold tolerance.
To evaluate the anti-inflammatory and neuroprotective effects of VCE-003.2 in LPS-lesioned mice, results showed that VCE-003.2 could reduce microglial activation and the loss of TH-positive neurons
J Neuroinflammation. 2018 Jan 16;15(1):19.
Kunming mice
Middle cerebral artery occlusion model (MCAO) in mice
Caudal vein injection
2 mg/kg
Single dose 1 h before MCAO surgery
T0070907 significantly reversed the protective effects of MA in MCAO mice, increased infarct size, and influenced the M1/M2 phenotype of microglia/macrophages.
J Neuroinflammation. 2015 Mar 14;12:51.
Mice
PPAR γflox/floxId2-CreERT2 mice
Intraperitoneal injection
7.5 mg/kg
Once daily for 18 days
To investigate the effect of T0070907 on tumor growth, results showed that T0070907 significantly reduced tumor volume and weight.
Nat Commun. 2021 May 5;12(1):2538.
BALB/c nu/nu mice
Pancreatic cancer xenograft model
Gavage
5 mg/kg
Three times a week for four weeks
T0070907 inhibited tumor growth without affecting the of mice.
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