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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. -
2015 Annual Meeting Abstract Supplement Late-Breaking Abstract Submissions
2015 Annual Meeting Abstract Supplement Late-Breaking Abstract Submissions All Late-Breaking Abstracts will be presented on Thursday, March 26, from 8:30 am–12:00 noon. These abstracts will be available via the mobile event app, online planner, and a downloadable PDF from the SOT website. 54th Annual Meeting and ToxExpoTM San Diego, California March 22–26, 2015 www.toxicology.org THURSDAY POSTER SESSION MAP March 2015—8:30 AM to 12:00 Noon—Sails Pavilion Poster Set Up—7:00 AM to 8:30 AM 260 259 258 257 256 301 302 303 304 305 660 659 658 657 656 251 252 253 254 255 310 309 308 307 306 651 652 653 654 655 250 249 248 247 246 311 312 313 314 315 650 649 648 647 646 241 242 243 244 245 320 319 318 317 316 641 642 643 644 645 240 239 238 237 236 321 322 323 324 325 640 639 638 637 636 231 232 233 234 235 330 329 328 327 326 631 632 633 634 635 230 229 228 227 226 331 332 333 334 335 630 629 628 627 626 221 222 223 224 225 340 339 338 337 336 621 622 623 624 625 220 219 218 217 216 341 342 343 344 345 620 619 618 617 616 211 212 213 214 215 350 349 348 347 346 611 612 613 614 615 210 209 208 207 206 351 352 353 354 355 610 609 608 607 606 201 202 203 204 205 360 359 358 357 356 601 602 603 604 605 170 169 168 167 166 401 402 403 404 405 570 569 568 567 566 161 162 163 164 165 410 409 408 407 406 561 562 563 564 565 160 159 158 157 156 411 412 413 414 415 560 559 558 557 556 151 152 153 154 155 420 419 418 417 416 551 552 553 554 555 150 149 148 147 146 421 422 423 424 425 550 549 548 547 546 141 142 143 144 145 430 429 428 427 426 541 542 -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
Disease Progression and Pharmacological Intervention in a Nutrient‑Defcient Rat Model of Nonalcoholic Steatohepatitis
Digestive Diseases and Sciences https://doi.org/10.1007/s10620-018-5395-7 ORIGINAL ARTICLE Disease Progression and Pharmacological Intervention in a Nutrient‑Defcient Rat Model of Nonalcoholic Steatohepatitis Kirstine S. Tølbøl1,3,4 · Birgit Stierstorfer2 · Jörg F. Rippmann2 · Sanne S. Veidal1 · Kristofer T. G. Rigbolt1 · Tanja Schönberger2 · Matthew P. Gillum4 · Henrik H. Hansen1 · Niels Vrang1 · Jacob Jelsing1 · Michael Feigh1 · Andre Broermann2 Received: 14 June 2018 / Accepted: 22 November 2018 © The Author(s) 2018 Abstract Background There is a marked need for improved animal models of nonalcoholic steatohepatitis (NASH) to facilitate the development of more efcacious drug therapies for the disease. Methods Here, we investigated the development of fbrotic NASH in male Wistar rats fed a choline-defcient L-amino acid- defned (CDAA) diet with or without cholesterol supplementation for subsequent assessment of drug treatment efcacy in NASH biopsy-confrmed rats. The metabolic profle and liver histopathology were evaluated after 4, 8, and 12 weeks of dieting. Subsequently, rats with biopsy-confrmed NASH were selected for pharmacological intervention with vehicle, elafbranor (30 mg/kg/day) or obeticholic acid (OCA, 30 mg/kg/day) for 5 weeks. Results The CDAA diet led to marked hepatomegaly and fbrosis already after 4 weeks of feeding, with further progression of collagen deposition and fbrogenesis-associated gene expression during the 12-week feeding period. Cholesterol supple- mentation enhanced the stimulatory efect of CDAA on gene transcripts associated with fbrogenesis without signifcantly increasing collagen deposition. Pharmacological intervention with elafbranor, but not OCA, signifcantly reduced stea- tohepatitis scores, and fbrosis-associated gene expression, however, was unable to prevent progression in fbrosis scores. -
Lipid Metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives
cancers Review Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives 1, 1, 1 2 1 Laurence Pellerin y, Lorry Carrié y , Carine Dufau , Laurence Nieto , Bruno Ségui , 1,3 1, , 1, , Thierry Levade , Joëlle Riond * z and Nathalie Andrieu-Abadie * z 1 Centre de Recherches en Cancérologie de Toulouse, Equipe Labellisée Fondation ARC, Université Fédérale de Toulouse Midi-Pyrénées, Université Toulouse III Paul-Sabatier, Inserm 1037, 2 avenue Hubert Curien, tgrCS 53717, 31037 Toulouse CEDEX 1, France; [email protected] (L.P.); [email protected] (L.C.); [email protected] (C.D.); [email protected] (B.S.); [email protected] (T.L.) 2 Institut de Pharmacologie et de Biologie Structurale, CNRS, Université Toulouse III Paul-Sabatier, UMR 5089, 205 Route de Narbonne, 31400 Toulouse, France; [email protected] 3 Laboratoire de Biochimie Métabolique, CHU Toulouse, 31059 Toulouse, France * Correspondence: [email protected] (J.R.); [email protected] (N.A.-A.); Tel.: +33-582-7416-20 (J.R.) These authors contributed equally to this work. y These authors jointly supervised this work. z Received: 15 September 2020; Accepted: 23 October 2020; Published: 27 October 2020 Simple Summary: Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids. -
A61p1/16 (2006.01) A61p3/00 (2006.01) Km, Ml, Mr, Ne, Sn, Td, Tg)
( (51) International Patent Classification: TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, A61P1/16 (2006.01) A61P3/00 (2006.01) KM, ML, MR, NE, SN, TD, TG). A61K 31/192 (2006.01) C07C 321/28 (2006.01) Declarations under Rule 4.17: (21) International Application Number: — as to the applicant's entitlement to claim the priority of the PCT/IB2020/000808 earlier application (Rule 4.17(iii)) (22) International Filing Date: Published: 25 September 2020 (25.09.2020) — with international search report (Art. 21(3)) (25) Filing Language: English — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of (26) Publication Language: English amendments (Rule 48.2(h)) (30) Priority Data: 62/906,288 26 September 2019 (26.09.2019) US (71) Applicant: ABIONYX PHARMA SA [FR/FR] ; 33-43 Av¬ enue Georges Pompidou, Batiment D, 31130 Bahna (FR). (72) Inventor: DASSEUX, Jean-Louis, Henri; 7 Allees Charles Malpel, Bat. B, 31300 Toulouse (FR). (74) Agent: HOFFMANN EITLE PATENT- UND RECHTSANWALTE PARTMBB, ASSOCIATION NO. 151; Arabellastrasse 30, 81925 Munich (DE). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, IT, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. -
Information to Users
INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Bell & Howell Information Company 300 North Zeeb Road, Ann Arbor, Ml 48106-1346 USA 313/761-4700 800/521-0600 Order Number 0211150 The role of fatty acids and related analogs in mediating peroxisome proliferation in primary cultures of rat hepatocytes Intrasuksri, Urusa, Ph.D. -
The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development
International Journal of Molecular Sciences Review The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development Fan Hong 1,2, Pengfei Xu 1,*,† and Yonggong Zhai 1,2,* 1 Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China; [email protected] 2 Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China * Correspondence: [email protected] (P.X.); [email protected] (Y.Z.); Tel.: +86-156-005-60991 (P.X.); +86-10-5880-6656 (Y.Z.) † Current address: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA. Received: 22 June 2018; Accepted: 24 July 2018; Published: 27 July 2018 Abstract: Peroxisome proliferator-activated receptors (PPARs) are a well-known pharmacological target for the treatment of multiple diseases, including diabetes mellitus, dyslipidemia, cardiovascular diseases and even primary biliary cholangitis, gout, cancer, Alzheimer’s disease and ulcerative colitis. The three PPAR isoforms (α, β/δ and γ) have emerged as integrators of glucose and lipid metabolic signaling networks. Typically, PPARα is activated by fibrates, which are commonly used therapeutic agents in the treatment of dyslipidemia. The pharmacological activators of PPARγ include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks. In this review, we summarize 84 types of PPAR synthetic ligands introduced to date for the treatment of metabolic and other diseases and provide a comprehensive analysis of the current applications and problems of these ligands in clinical drug discovery and development. -
Lessons from Liver-Specific PPAR-Null Mice
International Journal of Molecular Sciences Review PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice Yaping Wang 1, Takero Nakajima 1, Frank J. Gonzalez 2 and Naoki Tanaka 1,3,* 1 Department of Metabolic Regulation, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan; [email protected] (Y.W.); [email protected] (T.N.) 2 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] 3 Research Center for Social Systems, Shinshu University, Matsumoto, Nagano 390-8621, Japan * Correspondence: [email protected]; Tel.: +81-263-37-2851 Received: 21 February 2020; Accepted: 9 March 2020; Published: 17 March 2020 Abstract: Peroxisome proliferator-activated receptor (PPAR) α, β/δ, and γ modulate lipid homeostasis. PPARα regulates lipid metabolism in the liver, the organ that largely controls whole-body nutrient/energy homeostasis, and its abnormalities may lead to hepatic steatosis, steatohepatitis, steatofibrosis, and liver cancer. PPARβ/δ promotes fatty acid β-oxidation largely in extrahepatic organs, and PPARγ stores triacylglycerol in adipocytes. Investigations using liver-specific PPAR-disrupted mice have revealed major but distinct contributions of the three PPARs in the liver. This review summarizes the findings of liver-specific PPAR-null mice and discusses the role of PPARs in the liver. Keywords: PPAR; NAFLD; NASH; insulin resistance; liver fibrosis 1. Introduction Administration of Wy-14643, nafenopin, and fibrate drugs to rodents results in hepatic peroxisome proliferation. These agents are thus designated as peroxisome proliferators (PPs) [1]. To explain a mechanism of rapid and drastic changes following PP administration, the involvement of transcription factors was assumed and the first peroxisome proliferator-activated receptor (PPAR, later defined as PPARα (NR1C1)) was identified in 1990 [2]. -
Pemafibrate (K-877), a Novel Selective Peroxisome Proliferator-Activated
Fruchart Cardiovasc Diabetol (2017) 16:124 DOI 10.1186/s12933-017-0602-y Cardiovascular Diabetology REVIEW Open Access Pemafbrate (K‑877), a novel selective peroxisome proliferator‑activated receptor alpha modulator for management of atherogenic dyslipidaemia Jean‑Charles Fruchart* Abstract Despite best evidence-based treatment including statins, residual cardiovascular risk poses a major challenge for clini‑ cians in the twenty frst century. Atherogenic dyslipidaemia, in particular elevated triglycerides, a marker for increased triglyceride-rich lipoproteins and their remnants, is an important contributor to lipid-related residual risk, especially in insulin resistant conditions such as type 2 diabetes mellitus. Current therapeutic options include peroxisome proliferator-activated receptor alpha (PPARα) agonists, (fbrates), but these have low potency and limited selectivity for PPARα. Modulating the unique receptor–cofactor binding profle to identify the most potent molecules that induce PPARα-mediated benefcial efects, while at the same time avoiding unwanted side efects, ofers a new therapeutic approach and provides the rationale for development of pemafbrate (K-877, Parmodia™), a novel selective PPARα modulator (SPPARMα). In clinical trials, pemafbrate either as monotherapy or as add-on to statin therapy was efec‑ tive in managing atherogenic dyslipidaemia, with marked reduction of triglycerides, remnant cholesterol and apoli‑ poprotein CIII. Pemafbrate also increased serum fbroblast growth factor 21, implicated in metabolic homeostasis. There were no clinically meaningful adverse efects on hepatic or renal function, including no relevant serum creati‑ nine elevation. A major outcomes study, PROMINENT, will provide defnitive evaluation of the role of pemafbrate for management of residual cardiovascular risk in type 2 diabetes patients with atherogenic dyslipidaemia despite statin therapy. -
![Etomoxir, Sodium 2-[6-(4Chlorophenoxy)Hexyl]Oxirane-2-Carboxylate, Increases Uncoupling Protein-3 Mrna Levels in Primary Culture](https://docslib.b-cdn.net/cover/8939/etomoxir-sodium-2-6-4chlorophenoxy-hexyl-oxirane-2-carboxylate-increases-uncoupling-protein-3-mrna-levels-in-primary-culture-2878939.webp)
Etomoxir, Sodium 2-[6-(4Chlorophenoxy)Hexyl]Oxirane-2-Carboxylate, Increases Uncoupling Protein-3 Mrna Levels in Primary Culture
Diabetes Publish Ahead of Print, published online April 28, 2008 PPARβ/δ prevents NF-κB activation in adipocytes Activation of Peroxisome Proliferator-Activated Receptor β/δ (PPARβ/δ) Inhibits LPS-induced Cytokine Production in Adipocytes by Lowering NF-κB Activity via ERK1/2 Ricardo Rodríguez-Calvo1, Lucía Serrano1, Teresa Coll1, Norman Moullan2, Rosa M. Sánchez1, Manuel Merlos1, Xavier Palomer1, Juan C. Laguna1, Liliane Michalik2, Walter Wahli2 and Manuel Vázquez-Carrera1. 1Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, IBUB (Institut de Biomedicina de la UB), and CIBERDEM-Instituto de Salud Carlos III, Diagonal 643, E-08028 Barcelona, Spain and 2Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, CH-1015 Lausanne, Switzerland. Corresponding author: Manuel Vázquez-Carrera Unitat de Farmacologia. Facultat de Farmàcia. Diagonal 643. E-08028 Barcelona. Spain E-mail: [email protected] Received for publication 07 February 2008 and accepted in revised form 21 April 2008. Copyright American Diabetes Association, Inc., 2008 PPARβ/δ prevents NF-κB activation in adipocytes Objective: Chronic activation of the nuclear factor (NF)-κB in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether Peroxisome Proliferator-Activated Receptor (PPAR)β/δ activation prevents inflammation in adipocytes. Research Design and Methods and Results: Firstly, we examined whether the PPARβ/δ agonist GW501516 prevents LPS-induced cytokine production in differentiated 3T3-L1 adipocytes. Treatment with GW501516 blocked LPS-induced IL-6 expression and secretion by adipocytes and the subsequent activation of the STAT3-SOCS3 pathway. -
Role of PPAR and Its Agonist in Renal Diseases
Hindawi Publishing Corporation PPAR Research Volume 2010, Article ID 345098, 6 pages doi:10.1155/2010/345098 Review Article Role of PPARα and Its Agonist in Renal Diseases Ching-Feng Cheng,1, 2 Hsi-Hsien Chen,3 and Heng Lin4 1 Department of Medical Research, Tzu Chi General Hospital and Department of Pediatrics, Tzu Chi University, Hualien 970, Taiwan 2 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan 3 Graduate Institute of Clinical Medicine, Taipei Medical University and Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan 4 Graduate Institute of Pharmacology and Toxicology, Tzu Chi University, 701 Chung Yang Road, Section 3, Hualien 970, Taiwan Correspondence should be addressed to Heng Lin, [email protected] Received 17 June 2010; Accepted 17 October 2010 Academic Editor: Beatrice´ Desvergne Copyright © 2010 Ching-Feng Cheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Peroxisome proliferator-activated receptor (PPAR)-α, a member of a large nuclear receptor superfamily, plays a major role in the regulation of lipid metabolism. Recently, PPARα activation has been shown to confer additional benefits on endothelial function, kidney function, and anti-inflammation, suggesting that PPARα agonists may be good candidates for treating acute renal failure. In clinical application, PPAR-α activators, such as hypolipidemic drugs in fibric acid class, were proven to have therapeutic effects on metabolic syndrome and cardiovascular disease. This paper focuses on signaling pathways, ligand selectivity, and physio-pathological roles of PPARα in kidney diseases and the therapeutic utility of PPARα modulators in the treatment of diabetes and inflammation-induced nephropathy.