Targeting Ppars

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Natura Aonss Targeting PPARs: Coacatos Phamaceca Aonss Coeessos Anaonss/Paa Aonss A guide to function and structure PPAR α, δ, γ RR While PPARs display a high degree of homology at the protein level, each subtype exhibits distinct, noninter- PPRE DNA changeable roles in energy metabolism that range from energy burning to energy storage. Learn more about DA nn Hne Tage Gene ranscon their functions as fatty acid sensors and regulators of energy homeostasis at www.caymanchem.com/PPARs. www.caymanchem.com oman reon an nn oman A-1 A-2 NH2 COOH A/ C D E F MUSCLE PPARδ PPARα P se · ↑ Fatty acid oxidation · ↑ Fatty acid oxidation · ↑ Oxidative muscle fibers · ↑ Obesity resistance PPARγ PPARα* PPARδ PPARγ* · ↑ Insulin-mediated 1 99 173 239 466 468 1 71 145 211 439 441 1 136 210 238 503 505 · ↑ Insulin sensitivity glucose uptake A/ C D E F A/ C D E F A/ C D E F · ↑ Energy uncoupling Reesens sofom he canonca seence n nProt Reesens sofom he canonca seence n nProt FAAR NR1C2 Synonyms NR1C1 NR1C3 NUC1 LIVER PPARα PPARγ PPARβ · ↑ Fatty acid oxidation · ↑ Fatty acid storage · ↑ Ketogenesis · ↑ Lipogenesis CREBBP EP300 · ↓ Plasma triglycerides CITED2 FAM120B CREBBP MED1 (PBP/DRIP205/TRAP220) · ↑ Plasma HDL EP300 EP300 NCOA1 (RIP160/SRC-1) NCOA1 (RIP160/SRC-1) MED1 (PBP/DRIP205/TRAP220) NCOA2 (SRC-2) NCOA2 (SRC-2) Coactivators NCOA1 (RIP160/SRC-1) NCOA3 (SRC-3) NCOA3 (SRC-3) NCOA2 (SRC-2) NCOA4 PGC-1α NCOA3 (SRC-3) NCOA6 PGC-1α NCOA7 VESSEL WALL PPARα & PPARγ PGC-1β PGC-1α · ↓ Inflammation PRIC295 PGC-1β · ↑ Reverse cholesterol transport PGC-2 NCOR1 GPS2 PPARδ NCOR1 NR0B2 PER2 NCOR1 · ↓ Inflammation Corepressors RIP140 (NRIP1) RIP140 (NRIP1) RIP140 (NRIP1) NR0B1 SMRT (NCOR2) SMRT (NCOR2) SMRT (NCOR2) NR0B2 SPEN AM3102 Amorfrutin A Clofibrate Amorfrutin B WHITE ADIPOSE TISSUE PPARγ (+)-Etomoxir (sodium salt) Azelaoyl PAF · ↑ Adipogenesis Fenofibrate CAY10599 GW 590735 CAY10592 CDDO · Regulates adipokine production Selective Agonists GW 7647 GW 0742 Ciglitazone · ↑ Lipid repartitioning to fat GW 9578 GW 501516 GW 1929 8(S)-HETE Pioglitazone · ↑ Insulin sensitivity 12,14 Leukotriene B4 15-deoxy-Δ -Prostaglandin J2 · ↑ Lipogenesis N-Octadecyl-N’-propyl-sulfamide Rosiglitazone Oleoyl Ethanolamide Troglitazone Bavachinin (±)13-HODE Bavachinin Lanifibranor Bezafibrate Lanifibranor Bezafibrate Bavachinin MHY908 Non-Selective and CAY10514 MHY908 Elafibranor CAY10514 BROWN ADIPOSE TISSUE PPARδ Bezafibrate Muraglitazar Dual Agonists CAY10573 Muraglitazar Lanifibranor CAY10573 · ↑ Fatty acid oxidation CAY10573 Tesaglitazar Elafibranor Tesaglitazar (±)9-HODE Wy 14643 · ↑ Energy uncoupling (±)9-HODE Wy 14643 (±)13-HODE PPARγ BADGE GW 9662 Partial Agonists GSK3787 Diclofenac MCC-555 · ↑ Adipogenesis GW 6471 and Antagonists Sulindac FMOC-L-Leucine SR 202 G3335 T0070907.

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"This Is the Peer Reviewed Version of the Following Article: Murray, M., Dyari, H
"This is the peer reviewed version of the following article: Murray, M., Dyari, H. R. E., Allison, S. E. and Rawling, T. (2014), Lipid analogues as potential drugs for the regulation of mitochondrial cell death. British Journal of Pharmacology, 171: 2051–2066. doi: 10.1111/bph.12417 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bph.12417/abstract;jsessionid= 1A6A774DBD2AA9859B823125976041F6.f03t01 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." 1 Revised manuscript 2013-BJP-0609-RCT-G Lipid analogues as potential drugs for the regulation of mitochondrial cell death Michael Murray1, Herryawan Ryadi Eziwar Dyari1, Sarah E. Allison1 and Tristan Rawling2 1Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, University of Sydney, NSW 2006, Australia, and 2School of Pharmacy, Graduate School of Health, University of Technology, Sydney, PO Box 123, Broadway NSW 2007, Australia. Address for correspondence: Dr Michael Murray Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, Medical Foundation Building, Room 105, University of Sydney, NSW 2006, Australia Tel: (61-2-9036-3259) Fax (61-2-9036-3244) Email: [email protected] Running title: Lipids drugs to target mitochondrial cell death 2 Abstract The mitochondrion has fundamental roles in the production of energy as ATP, the regulation of cell viability and apoptosis, and the biosynthesis of major structural and regulatory molecules, such as lipids. During ATP production reactive oxygen species are generated that alter the intracellular redox state and activate apoptosis. Mitochondrial dysfunction is a well recognized component of the pathogenesis of diseases such as cancer.
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