17138-28-2Relevant articles and documents
Seven-membered fused ring compound and organic photovoltaic cell
-
Paragraph 0043-0051, (2021/03/23)
The invention discloses a seven-membered fused ring compound shown as a formula (I) and an organic photovoltaic cell containing the seven-membered fused ring compound. When the seven-membered fused ring compound is used as a non-fullerene organic electron acceptor material, a relatively environment-friendly chlorine-free solvent can be used for coating in the manufacturing process of an organic photovoltaic cell, and meanwhile, the high energy conversion efficiency (PCE) of the organic photovoltaic cell can be maintained;.
L-Thyroxin and the Nonclassical Thyroid Hormone TETRAC Are Potent Activators of PPAR?
Gellrich, Leonie,Heitel, Pascal,Heering, Jan,Kilu, Whitney,Pollinger, Julius,Goebel, Tamara,Kahnt, Astrid,Arifi, Silvia,Pogoda, Werner,Paulke, Alexander,Steinhilber, Dieter,Proschak, Ewgenij,Wurglics, Mario,Schubert-Zsilavecz, Manfred,Chaikuad, Apirat,Knapp, Stefan,Bischoff, Iris,Fürst, Robert,Merk, Daniel
, p. 6727 - 6740 (2020/09/11)
Thyroid hormones (THs) operate numerous physiological processes through modulation of the nuclear thyroid hormone receptors and several other proteins. We report direct activation of the nuclear peroxisome proliferator-activated receptor gamma (PPAR?) and retinoid X receptor (RXR) by classical and nonclassical THs as another molecular activity of THs. The T4 metabolite TETRAC was the most active TH on PPARγwith nanomolar potency and binding affinity. We demonstrate that TETRAC promotes PPAR?/RXR signaling in cell-free, cellular, and in vivo settings. Simultaneous activation of the heterodimer partners PPARγand RXR resulted in high dimer activation efficacy. Compared to fatty acids as known natural ligands of PPARγand RXR, TETRAC differs markedly in its molecular structure and the PPAR?-TETRAC complex revealed a distinctive binding mode of the TH. Our observations suggest a potential connection of TH and PPAR signaling through overlapping ligand recognition and may hold implications for TH and PPAR pharmacology.
Design and Structural Optimization of Dual FXR/PPARδActivators
Schierle, Simone,Neumann, Sebastian,Heitel, Pascal,Willems, Sabine,Kaiser, Astrid,Pollinger, Julius,Merk, Daniel
supporting information, p. 8369 - 8379 (2020/08/12)
Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of the metabolic syndrome and has alarming global prevalence. The ligand-activated transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) δhave been validated as molecular targets to counter NASH. To achieve robust therapeutic efficacy in this multifactorial pathology, combined peripheral PPAR?-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approach. We have designed a minimal dual FXR/PPARδactivator scaffold by rational fusion of pharmacophores derived from selective agonists. Our dual agonist lead compound exhibited weak agonism on FXR and PPARδand was structurally refined to a potent and balanced FXR/PPARδactivator in a computer-aided fashion. The resulting dual FXR/PPARδmodulator comprises high selectivity over related nuclear receptors and activates the two target transcription factors in native cellular settings.