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Overview
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Background
T0070907 is a selective antagonist of peroxisome proliferator-activated receptor γ (PPARγ) with IC50 value of 1nM [1].T0070907 shows high affinity to PPARγ with Ki of 1nM. The Ki values of it to PPARα and PPARδ are 0.85 and 1.8μM, respectively, demonstrating the high selectivity of T0070907. It is found that T0070907 binds PPARγ within the cysteine 313 in helix 3 of human PPARγ2, subsequently blocks PPARγ function. In transient transfection assay, T0070907 inhibits the transactivation of PPARγ in the presence of rosiglitazone (a PPARγ agonist) with IC50 value in the nM range. T0070907 can block the induction of adipogenesis of the adipogenic cell line 3T3-L1. Additionally, T0070907 is found to suppress the interaction between PPARγ and the coactivator derived peptide, while promoting the recruitment of the NCoR-derived peptide to PPARγ. Furthermore, T0070907 can also promote a significant increase in the recruitment of NCoR to the PPARγ/RXRα heterodimer [1].
[1] Lee G, Elwood F, McNally J, Weiszmann J, Lindstrom M, Amaral K, Nakamura M, Miao S, Cao P, Learned RM, Chen JL, Li Y. T0070907, a selective ligand for peroxisome proliferator-activated receptor gamma, functions as an antagonist of biochemical and cellular activities. J Biol Chem. 2002 May 31;277(22):19649-57.
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