DOCSLIB.ORG

Avanti Price List January 2015

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Avanti Price List January 2015 AVANTI PRICE LIST JANUARY 2015 Lipidomics Products Monoclonal Antibodies, Lipid Snoopers®, Lipidomix Toolbox, MS Standards General Products Sphingolipids Sphingosines, Ceramides, SM, Glycosphingolipids, Phytosphingosines, Inhibitors, Agonists Phospholipids PC, PA, PE, PG, PS, PI, PIP, CA, Lysos, BMP, Ether Lipids, Plasmalogens, Bicelle Preparation Sterols Natural Sterols, Substituted Oxysterols & Derivatives Bioactive Lipids Adjuvants, IP’s, Agonists, PAF, Cyclic LPA, Bioactive Cer., Endocannabinoids, DGPP, Lysyl PG Coenzyme A & Derivatives Coenzyme A, Acyl CoA - Saturated Fatty Acid & Unsaturated Fatty Acid, Derivatives Neutral Lipids Diacyl Glycerols & Analogs, Prostaglandins, Prenol Fatty Acid Modified Lipids Brominated, Fluorinated, Biotinylated, Diphytanoyl, Oxidized, Misc. Headgroup Modified Lipids Chelators, Functionalized, Antigenic, pH Sensitive, Glycosylated, Alkyl Phosphates Cationic Lipids (Transfection) DC-Cholesterol, DOTAP, DOTMA, DODAP, DDAB, & Ethyl PC Detergents Nonionic, Anionic, Zwitterionic, Lyso PC & PG, Short chain PC Formulations & Blends Lipid Blends, Lipids for Bicelles, Doxorubicin Nano-Drug, Captisome™ Stable Isotopes & ESR Probes Deuterated Sphingolipids & Phospholipids, Doxyl PC & Probe, Tempo PC, ESR Probes Fluorescent Lipids Sphingolipids, Bioactive Lipids, Cationic Lipid, Fluorescent Marker, Phospholipids, Sterols Polymers & Polymerizable Lipids Crosslinking Lipids, PEG Phospholipids, PEG Ceramides, Functionalized PEG Lipids Aurora™ Gold Probes & Standards, Analytical Services Soy Analytical Standard, TLC Standards Bulk Lipids for Pharmaceuticals cGMP Products Equipment, Storage & Handling and Numerical Index Sonicator, Mini-Extruder, Super G Balance, Packaging Containers ORDERING INFORMATION PRICES LISTED The price is shown for standard quantities, although packing and shipping costs are not included. Avanti® is pleased to supply lipids in any quantity; please call for a quote for your special requirements. SYNTHESIZED ON REQUEST As product purity is Avanti’s primary concern we routinely synthesize products when ordered. Where this Price List designates “Synthesized on Request” call to advise the quantity required and we will be pleased to quote price and delivery. CUSTOM SYNTHESIS Avanti® regularly performs custom syntheses of lipids for its customers worldwide. We welcome your suggestions for new products. CGMP LIPIDS Avanti® routinely synthesizes products to cGMP Standards for bulk pharmaceutical production and some of these, currently in production, are listed on pages 95 & 96. We are pleased to discuss the production of any lipid to cGMP Standard. ORDER There is a $100.00 minimum order requirement and you may order by phone, FAX or Email. The minimum quantity of any product, available at list price, may be found in this Price List. Please provide the following information: •Avanti Customer Number •Shipping Information •P.O. Number •Item Product Number •Quantity •Unit Size •Physical State (Powder or Solution) Note: A Confirming purchase order is not required. However, if you wish to send one, please label the purchase order as “Confirming” and reference the Avanti order number to avoid costly duplicate shipments. ACCESS NUMBERS USA/Canada (800) 227-0651 or (205) 663-2494 FAX USA/Canada (800) 229-1004 or (205) 663-0756 OFFICE HOURS 7:30 AM - 5:00 PM Central Standard Time MAILING ADDRESS Avanti® Polar Lipids, Inc., 700 Industrial Park Drive, Alabaster, AL 35007-9105, U.S.A. EMAIL Orders: [email protected] Inquiries: [email protected] Technical questions: [email protected] Analytical: [email protected] E-COMMERCE You may also order on line at www.avantilipids.com INTERNATIONAL ORDERS International clients are invited to contact their nearest distributor. For a convenient list of Distributors visit www.avantilipids.com or call us today. GENERAL INFORMATION CGMP FACILITIES Avanti® operates a bulk pharmaceutical facility registered with the U.S. Food & Drug Administration (FDA) and complies with the guidelines of current Good Manufacturing Practice (cGMP). We have a select group of products for which Drug Master Files have been registered with the FDA. CERTIFICATE OF ANALYSIS Research Certificate of Analysis consist of a TLC (Thin Layer Chromatography) on each compound in our catalog. It is intended only for qualitative purity and identity of each compound. Expiration dates for research products are given as the period of time Avanti® will guarantee the product quality from the date of shipment (assuming proper storage and handling by customer). It is possible that the product may be acceptable far beyond the expiration date, however, since this time will be variable (dependent on customer handling and storage conditions), Avanti® cannot guarantee its acceptability beyond the expiration. Requests for Certificates of Analysis on research products must be made at the time of order. CGMP CERTIFICATE OF ANALYSIS GMP Certificate of Analysis consists of full release testing according to approved specifications and is performed only on those compounds made according to current Good Manufacturing Practice guidelines for human drug products or diagnostics. Expiration dating of cGMP materials is based on stability studies performed by Avanti® at the recommended storage temperature. The expiration date is assigned from the date of manufacture and may be extended after mandatory retesting at intervals. WARNING The majority of Avanti® products are sold for research use only. Most are not for Diagnostic Procedures pursuant to 21 CFR 809.10. Any other use requires FDA clearance. MATERIAL SAFETY DATA SHEETS An MSDS is provided to our customers for each product shipped as required by the OSHA Hazard Communication Standard and many state laws. Upon request, MSDS’s are available to customers for previously purchased products. Avanti® is dedicated to safety. CUSTOM PACKAGING Avanti’s products are available in a variety of different packaging and physical states. There is a packaging charge of $3.00 per ampule if the product is divided into multiple ampules. GENERAL INFORMATION AVANTI PRICING POLICY Avanti® reserves the right to change prices at any time. To ascertain the most recent price for any of our products, and for recent developments, visit www.avantilipids.com. RETURNED PRODUCTS POLICY No product may be returned without prior authorization from Avanti®. Requests to return products must be made within 10 days of receipt. If an error is made in placing or filling your order, please advise us promptly, so that we may take the proper action. Returned products should be clearly marked with the sender’s name and address, carefully packed, and shipped prepaid at the beginning of the week to arrive within the same work week. Products must be returned in the same condition as received within 15 days of original shipment by Avanti®. LIMITED WARRANTY Avanti® guarantees its products to the original purchaser as to identity and purity as specified. You, the customer, are our most important asset. If you are not completely satisfied with any aspect of Avanti’s product, we will either replace the product at no cost to you or refund your money. Avanti® does not make any warranty, express or implied, with respect to its products, services or any other matter, except as specifically set forth above, and Avanti® hereby expressly disclaims all warranties, express and implied, with respect to its products, services and other matters, including, but not limited to, the implied warranties (if any) of merchantability and fitness for a particular purpose. In the event of any breach of the limited warranty set forth above, Avanti® shall, at Avanti’s election, replace the product in question or provide the purchaser with a refund of the purchase price for the product in question. The foregoing is the purchaser’s sole and exclusive remedy for a breach of the limited warranty set forth above. In no event shall Avanti® be liable to the purchaser or any third party for any incidental or consequential damages (including, without limitation, indirect, special, punitive, or exemplary damages or damages for loss of business, loss of data, loss of profits, loss of goodwill or business reputation, business interruption, loss of data, or loss of business information) arising out of or connected in any way with its products or services, or for any claim by any third party even if Avanti® has been advised of the possibility of such damages. In addition to the foregoing limitation, in no event shall Avanti® liability in connection with any of its products, under any theory or form of action (whether contract, tort, warranty, indemnity, or otherwise) exceed the purchase price of the Avanti® product in question. No claim arising in connection with this agreement or the products or services contemplated hereby may be brought against Avanti® more than one year after it accrues. cGMP Manufacturing Avanti Polar Lipids, Inc Alabaster Campus 2014 For over 40 years Avanti has provided API (Active Pharma- ceutical Ingredient) Technology Development for Pharma- ceutical and Biotechnology companies. Our unique reputa- tion for quality in the development of pre-clinical and clinical candidates is well established. Our full range of services include process chemistry, scale-up manufacturing, supply chain management with analytical and regulatory require- ments. Avanti’s experienced staff of chemists and lipid analysts are ready to meet your development needs with pre-clinical through phase III and commercial launch. To order
Load more

Recommended publications
  • Retinamide Increases Dihydroceramide and Synergizes with Dimethylsphingosine to Enhance Cancer Cell Killing
    2967 N-(4-Hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethylsphingosine to enhance cancer cell killing Hongtao Wang,1 Barry J. Maurer,1 Yong-Yu Liu,2 elevations in dihydroceramides (N-acylsphinganines), Elaine Wang,3 Jeremy C. Allegood,3 Samuel Kelly,3 but not desaturated ceramides, and large increases in Holly Symolon,3 Ying Liu,3 Alfred H. Merrill, Jr.,3 complex dihydrosphingolipids (dihydrosphingomyelins, Vale´rie Gouaze´-Andersson,4 Jing Yuan Yu,4 monohexosyldihydroceramides), sphinganine, and sphin- Armando E. Giuliano,4 and Myles C. Cabot4 ganine 1-phosphate. To test the hypothesis that elevation of sphinganine participates in the cytotoxicity of 4-HPR, 1Childrens Hospital Los Angeles, Keck School of Medicine, cells were treated with the sphingosine kinase inhibitor University of Southern California, Los Angeles, California; D-erythro-N,N-dimethylsphingosine (DMS), with and 2 College of Pharmacy, University of Louisiana at Monroe, without 4-HPR. After 24 h, the 4-HPR/DMS combination Monroe, Louisiana; 3School of Biology and Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, caused a 9-fold increase in sphinganine that was sustained Atlanta, Georgia; and 4Gonda (Goldschmied) Research through +48 hours, decreased sphinganine 1-phosphate, Laboratories at the John Wayne Cancer Institute, and increased cytotoxicity. Increased dihydrosphingolipids Saint John’s Health Center, Santa Monica, California and sphinganine were also found in HL-60 leukemia cells and HT-29 colon cancer cells treated with 4-HPR. The Abstract 4-HPR/DMS combination elicited increased apoptosis in all three cell lines. We propose that a mechanism of N Fenretinide [ -(4-hydroxyphenyl)retinamide (4-HPR)] is 4-HPR–induced cytotoxicity involves increases in dihy- cytotoxic in many cancer cell types.
    [Show full text]
  • Anticancer Effects of Vitamin E Forms and Their Long-Chain Metabolites Via Modulation of Sphingolipid Metabolism Yumi Jang Purdue University
    Purdue University Purdue e-Pubs Open Access Dissertations Theses and Dissertations January 2015 Anticancer Effects of Vitamin E Forms and Their Long-chain Metabolites via Modulation of Sphingolipid Metabolism Yumi Jang Purdue University Follow this and additional works at: https://docs.lib.purdue.edu/open_access_dissertations Recommended Citation Jang, Yumi, "Anticancer Effects of Vitamin E Forms and Their Long-chain Metabolites via Modulation of Sphingolipid Metabolism" (2015). Open Access Dissertations. 1119. https://docs.lib.purdue.edu/open_access_dissertations/1119 This document has been made available through Purdue e-Pubs, a service of the Purdue University Libraries. Please contact [email protected] for additional information. Graduate School Form 30 Updated 1/15/2015 PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance This is to certify that the thesis/dissertation prepared By Yumi Jang Entitled Anticancer Effects of Vitamin E Forms and Their Long-chain Metabolites via Modulation of Sphingolipid Metabolism For the degree of Doctor of Philosophy Is approved by the final examining committee: Qing Jiang Chair Dorothy Teegarden John R. Burgess Yava Jones-Hall To the best of my knowledge and as understood by the student in the Thesis/Dissertation Agreement, Publication Delay, and Certification Disclaimer (Graduate School Form 32), this thesis/dissertation adheres to the provisions of Purdue University’s “Policy of Integrity in Research” and the use of copyright material. Approved by Major Professor(s): Qing Jiang Approved by: Connie M. Weaver 9/2/2015 Head of the Departmental Graduate Program Date i ANTICANCER EFFECTS OF VITAMIN E FORMS AND THEIR LONG-CHAIN METABOLITES VIA MODULATION OF SPHINGOLIPID METABOLISM A Dissertation Submitted to the Faculty of Purdue University by Yumi Jang In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December 2015 Purdue University West Lafayette, Indiana ii ACKNOWLEDGEMENTS I owe a debt of gratitude to many people who have made this dissertation possible.
    [Show full text]
  • Cardiolipin and Mitochondrial Cristae Organization
    Biochimica et Biophysica Acta 1859 (2017) 1156–1163 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Cardiolipin and mitochondrial cristae organization Nikita Ikon, Robert O. Ryan ⁎ Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, United States article info abstract Article history: A fundamental question in cell biology, under investigation for over six decades, is the structural organization of Received 23 December 2016 mitochondrial cristae. Long known to harbor electron transport chain proteins, crista membrane integrity is key Received in revised form 3 March 2017 to establishment of the proton gradient that drives oxidative phosphorylation. Visualization of cristae morphol- Accepted 18 March 2017 ogy by electron microscopy/tomography has provided evidence that cristae are tube-like extensions of the mito- Available online 20 March 2017 chondrial inner membrane (IM) that project into the matrix space. Reconciling ultrastructural data with the lipid Keywords: composition of the IM provides support for a continuously curved cylindrical bilayer capped by a dome-shaped Cardiolipin tip. Strain imposed by the degree of curvature is relieved by an asymmetric distribution of phospholipids in Mitochondria monolayer leaflets that comprise cristae membranes. The signature mitochondrial lipid, cardiolipin (~18% of Cristae IM phospholipid mass), and phosphatidylethanolamine (34%) segregate to the negatively curved monolayer leaf- Membrane curvature let facing the crista lumen while the opposing, positively curved, matrix-facing monolayer leaflet contains pre- Non-bilayer lipid dominantly phosphatidylcholine. Associated with cristae are numerous proteins that function in distinctive Electron transport chain ways to establish and/or maintain their lipid repertoire and structural integrity.
    [Show full text]
  • A Phase I Clinical Trial of Safingol in Combination with Cisplatin in Advanced Solid Tumors
    Published OnlineFirst January 21, 2011; DOI: 10.1158/1078-0432.CCR-10-2323 Clinical Cancer Cancer Therapy: Clinical Research A Phase I Clinical Trial of Safingol in Combination with Cisplatin in Advanced Solid Tumors Mark A. Dickson1, Richard D. Carvajal1, Alfred H. Merrill, Jr.3, Mithat Gonen2, Lauren M. Cane1, and Gary K. Schwartz1 Abstract Purpose: Sphingosine 1-phosphate (S1P) is an important mediator of cancer cell growth and pro- liferation. Production of S1P is catalyzed by sphingosine kinase 1 (SphK). Safingol, (L-threo-dihydro- sphingosine) is a putative inhibitor of SphK. We conducted a phase I trial of safingol (S) alone and in combination with cisplatin (C). Experimental Design: A3þ 3 dose escalation was used. For safety, S was given alone 1 week before the combination. S þ C were then administered every 3 weeks. S was given over 60 to 120 minutes, depending on dose. Sixty minutes later, C was given over 60 minutes. The C dose of 75 mg/m2 was reduced in cohort 4 to 60 mg/m2 due to excessive fatigue. Results: Forty-three patients were treated, 41 were evaluable for toxicity, and 37 for response. The maximum tolerated dose (MTD) was S 840 mg/m2 over 120 minutes C 60 mg/m2, every 3 weeks. Dose- limiting toxicity (DLT) attributed to cisplatin included fatigue and hyponatremia. DLT from S was hepatic enzyme elevation. S pharmacokinetic parameters were linear throughout the dose range with no significant interaction with C. Patients treated at or near the MTD achieved S levels of more than 20 mmol/L and maintained levels greater than and equal to 5 mmol/L for 4 hours.
    [Show full text]
  • Protein Kinase C ␣/␤ Inhibitor Go6976 Promotes Formation of Cell Junctions and Inhibits Invasion of Urinary Bladder Carcinoma Cells
    [CANCER RESEARCH 64, 5693–5701, August 15, 2004] Protein Kinase C ␣/␤ Inhibitor Go6976 Promotes Formation of Cell Junctions and Inhibits Invasion of Urinary Bladder Carcinoma Cells Jussi Koivunen,1 Vesa Aaltonen,1 Sanna Koskela,1,3 Petri Lehenkari,1,3 Matti Laato,4,5 and Juha Peltonen1,2,5 Departments of 1Anatomy and Cell Biology and 2Dermatology, University of Oulu, Oulu, Finland; 3Department of Surgery, Clinical Research Center, University of Oulu, Oulu, Finland; 4Department of Surgery, Turku University Central Hospital, Turku, Finland; and 5Department of Medical Biochemistry, University of Turku, Turku, Finland ABSTRACT drugs in cell cultures and animal models (14–19). Furthermore, isoen- zyme-specific PKC inhibitors seem to be more effective anticancer Changes in activation balance of different protein kinase C (PKC) drugs than broad-spectrum inhibitors, suggesting the role of PKC isoenzymes have been linked to cancer development. The current study activation balance in cancer (20). investigated the effect of different PKC inhibitors on cellular contacts in cultured high-grade urinary bladder carcinoma cells (5637 and T24). Epithelial cells have abundant cell-cell junctions, which have a Exposure of the cells to isoenzyme-specific PKC inhibitors yielded vari- critical role in cell behavior and tissue morphogenesis. The most able results: Go6976, an inhibitor of PKC␣ and PKC␤ isoenzymes, in- important anchoring structures between epithelial cells are adherens duced rapid clustering of cultured carcinoma cells and formation of an junctions and desmosomes. Adherens junctions are composed of increased number of desmosomes and adherens junctions. Safingol, a transmembrane cadherin proteins; ␤-catenin, which attaches to cyto- PKC␣ inhibitor, had similar but less pronounced effects.
    [Show full text]
  • Serum from Pediatric Dilated Cardiomyopathy Patients Causes Dysregulation of Cardiolipin Biosynthesis and Mitochondrial Function Julie Pires Da Silva, Anastacia M
    Serum From Pediatric Dilated Cardiomyopathy Patients Causes Dysregulation of Cardiolipin Biosynthesis and Mitochondrial Function Julie Pires Da Silva, Anastacia M. Garcia, Carissa A. Miyano, Genevieve C. Sparagna, Raleigh Jonscher, Hanan Elajaili, and Carmen C. Sucharov. University of Colorado Anschutz Medical Campus, Aurora, CO Dilated Cardiomyopathy (DCM) Hypothesis - Dilated cardiomyopathy (DCM) is defined as a disorder characterized by Using a novel in vitro model of DCM-related cardiomyocyte remodeling that dilation and impaired contraction of the left ventricle or both ventricles. reproduces the molecular characteristics of pediatric DCM, we hypothesized that the alteration of mitochondrial function in NRVM treated - DCM is the most common form of cardiomyopathy and cause of heart with DCM pediatric sera is associate with changes in cardiolipin content and failure in children older than 1 year of age with an annual incidence of 0.57 mitochondrial β-oxidation pathway. per 100,000 children. - The causes of heart failure (HF) in children differ substantially from those Results found in the adult population and children do not respond well to adult HF therapies. Cardiolipin (CL) - Cardiolipin is a mitochondrial dimeric phospholipid normally located in the inner mitochondrial membrane Figure 5. DCM serum induces significant changes in metabolite levels involved in fatty acid oxidation pathway in NRVMs. A. Heatmap of 41 - CL represent 12-15% of phospholipid mass in heart. In the metabolites differentially expressed in NF and DCM serum-treated NRVMs. n = 4 NF, n= 4 DCM samples, p<0.05. B. Pathway enrichment map analysis heart, 70-80% is (18:2)4CL. of differential metabolites between NF and DCM groups using Figure 3.
    [Show full text]
  • Altered Traffic of Cardiolipin During Apoptosis: Exposure on the Cell Surface As a Trigger for (Antiphospholipid Antibodies)
    Hindawi Publishing Corporation Journal of Immunology Research Volume 2015, Article ID 847985, 9 pages http://dx.doi.org/10.1155/2015/847985 Review Article Altered Traffic of Cardiolipin during Apoptosis: Exposure on the Cell Surface as a Trigger for (Antiphospholipid Antibodies) Valeria Manganelli,1 Antonella Capozzi,1 Serena Recalchi,1 Michele Signore,2 Vincenzo Mattei,1,3 Tina Garofalo,1 Roberta Misasi,1 Mauro Degli Esposti,4 and Maurizio Sorice1 1 Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy 2Department of Hematology, Oncology and Molecular Medicine, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy 3Laboratory of Experimental Medicine and Environmental Pathology, Sabina Universitas, Via dell’Elettronica, 02100 Rieti, Italy 4Italian Institute of Technology, Via Morego 30, 16136 Genoa, Italy Correspondence should be addressed to Maurizio Sorice; [email protected] Received 27 July 2015; Accepted 6 September 2015 Academic Editor: Douglas C. Hooper Copyright © 2015 Valeria Manganelli 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. Apoptosis has been reported to induce changes in the remodelling of membrane lipids; after death receptor engagement, specific changes of lipid composition occur not only at the plasma membrane, but also in intracellular membranes. This paper focuses on one important aspect of apoptotic changes in cellular lipids, namely, the redistribution of the mitochondria-specific phospholipid, cardiolipin (CL). CL predominantly resides in the inner mitochondrial membrane, even if the rapid remodelling of its acyl chains and the subsequent degradation occur in other membrane organelles.
    [Show full text]
  • (MAP) Kinase Pathway
    Leukemia (1998) 12, 1843–1850 1998 Stockton Press All rights reserved 0887-6924/98 $12.00 http://www.stockton-press.co.uk/leu REVIEW The roles of signaling by the p42/p44 mitogen-activated protein (MAP) kinase pathway; a potential route to radio- and chemo-sensitization of tumor cells resulting in the induction of apoptosis and loss of clonogenicity P Dent1,2, WD Jarvis3, MJ Birrer4, PB Fisher5, RK Schmidt-Ullrich1 and S Grant2,3,6 Departments of 1Radiation Oncology, 3Medicine, 2Pharmacology and Toxicology, and 6Microbiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA; 4National Cancer Institute, Biomarkers Branch, Division of Clinical Sciences, Rockville, MD; 5Columbia University College of Physicians and Surgeons, Department of Pathology and Urology, New York, NY, USA During the last 10 years, multiple signal transduction pathways terized dual specificity (threonine/tyrosine) protein kinase.4–6 within cells have been discovered. These pathways have been The use of the nomenclature MAPKK/MKK has declined, and linked to the regulation of many diverse cellular events such as proliferation, senescence, differentiation and apoptosis. this enzyme is more frequently referred to as MEK (mitogen This review will focus upon the many roles of signaling by the activated/extracellular regulated kinase). Shortly after the dis- p42/p44 mitogen-activated protein (MAP) kinase pathway. covery of MEK, a second isoform of this enzyme was identified Recent evidence suggests that signaling by the MAP kinase (MEK1 and MEK2).7 MEK1/2 were also found to be regulated pathway can both enhance proliferation by increased by reversible phosphorylation, and within 6 months of the dis- expression of molecules such as cyclin D1, but also cause covery of MEK2, the protein kinase responsible for catalyzing growth arrest by increased expression of molecules such as Cip-1/MDA6/WAF1 MEK1/2 activation was discovered, the proto-oncogene the cyclin kinase inhibitor protein p21 .
    [Show full text]
  • Role of Calcium-Independent Phospholipase A2 in the Pathogenesis of Barth Syndrome
    Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome Ashim Malhotraa, Irit Edelman-Novemskyb, Yang Xua, Heide Pleskenb, Jinping Mab, Michael Schlamea,b, and Mindong Renb,1 Departments of bCell Biology and aAnesthesiology, New York University Langone Medical Center, New York, NY 10016 Edited by David D. Sabatini, New York University School of Medicine, New York, NY, and approved December 23, 2008 (received for review November 6, 2008) Quantitative and qualitative alterations of mitochondrial cardio- is required for maintaining not only the normal CL fatty acyl lipin have been implicated in the pathogenesis of Barth syndrome, composition, but also normal CL levels. an X-linked cardioskeletal myopathy caused by a deficiency in Although it has been established that tafazzin deficiency tafazzin, an enzyme in the cardiolipin remodeling pathway. We causes both Barth syndrome and a derangement of CL metab- have generated and previously reported a tafazzin-deficient Dro- olism, evidence that it is, in fact, the CL deficiency that con- sophila model of Barth syndrome that is characterized by low tributes to Barth syndrome has been circumstantial (15). To cardiolipin concentration, abnormal cardiolipin fatty acyl compo- elucidate the pathogenic mechanism of Barth syndrome and to sition, abnormal mitochondria, and poor motor function. Here, we identify potential targets for therapeutic intervention, we have first show that tafazzin deficiency in Drosophila disrupts the final created a Drosophila model of Barth syndrome (7) by knocking stage of spermatogenesis, spermatid individualization, and causes out the tafazzin gene and have asked whether the resulting male sterility. This phenotype can be genetically suppressed by phenotypic changes can be suppressed by partially restoring CL inactivation of the gene encoding a calcium-independent phos- homeostasis without correcting the tafazzin defect.
    [Show full text]
  • Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy
    cancers Review Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy Preeti Gupta 1, Aaliya Taiyab 1 , Afzal Hussain 2, Mohamed F. Alajmi 2, Asimul Islam 1 and Md. Imtaiyaz Hassan 1,* 1 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India; [email protected] (P.G.); [email protected] (A.T.); [email protected] (A.I.) 2 Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; afi[email protected] (A.H.); [email protected] (M.F.A.) * Correspondence: [email protected] Simple Summary: Cancer is the prime cause of death globally. The altered stimulation of signaling pathways controlled by human kinases has often been observed in various human malignancies. The over-expression of SphK1 (a lipid kinase) and its metabolite S1P have been observed in various types of cancer and metabolic disorders, making it a potential therapeutic target. Here, we discuss the sphingolipid metabolism along with the critical enzymes involved in the pathway. The review provides comprehensive details of SphK isoforms, including their functional role, activation, and involvement in various human malignancies. An overview of different SphK inhibitors at different phases of clinical trials and can potentially be utilized as cancer therapeutics has also been reviewed. Citation: Gupta, P.; Taiyab, A.; Hussain, A.; Alajmi, M.F.; Islam, A.; Abstract: Sphingolipid metabolites have emerged as critical players in the regulation of various Hassan, M..I. Targeting the Sphingosine Kinase/Sphingosine- physiological processes. Ceramide and sphingosine induce cell growth arrest and apoptosis, whereas 1-Phosphate Signaling Axis in Drug sphingosine-1-phosphate (S1P) promotes cell proliferation and survival.
    [Show full text]
  • Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/Ipla2γ with Fatty Acid–Conducting SLC25 Gene Family Transporters
    antioxidants Review Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid–Conducting SLC25 Gene Family Transporters Martin Jab ˚urek 1,* , Pavla Pr ˚uchová 1, Blanka Holendová 1 , Alexander Galkin 2 and Petr Ježek 1 1 Department of Mitochondrial Physiology, Institute of Physiology of the Czech Academy of Sciences, Vídeˇnská 1084, 14220 Prague, Czech Republic; [email protected] (P.P.); [email protected] (B.H.); [email protected] (P.J.) 2 Department of Pediatrics, Division of Neonatology, Columbia University William Black Building, New York, NY 10032, USA; [email protected] * Correspondence: [email protected]; Tel.: +420-296442789 Abstract: Patatin-like phospholipase domain-containing protein PNPLA8, also termed Ca2+-independent phospholipase A2γ (iPLA2γ), is addressed to the mitochondrial matrix (or peroxisomes), where it may manifest its unique activity to cleave phospholipid side-chains from both sn-1 and sn-2 posi- tions, consequently releasing either saturated or unsaturated fatty acids (FAs), including oxidized FAs. Moreover, iPLA2γ is directly stimulated by H2O2 and, hence, is activated by redox signaling or oxidative stress. This redox activation permits the antioxidant synergy with mitochondrial un- coupling proteins (UCPs) or other SLC25 mitochondrial carrier family members by FA-mediated Citation: Jab ˚urek, M.; Pr ˚uchová,P.; protonophoretic activity, termed mild uncoupling, that leads to diminishing of mitochondrial su- Holendová, B.; Galkin, A.; Ježek, P. peroxide formation. This mechanism allows for the maintenance of the steady-state redox status of Antioxidant Synergy of the cell. Besides the antioxidant role, we review the relations of iPLA2γ to lipid peroxidation since Mitochondrial Phospholipase iPLA2γ is alternatively activated by cardiolipin hydroperoxides and hypothetically by structural γ PNPLA8/iPLA2 with Fatty alterations of lipid bilayer due to lipid peroxidation.
    [Show full text]
  • Compounds As Lysophosphatidic Acid
    (19) TZZ _ _T (11) EP 2 462 128 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 261/14 (2006.01) C07D 413/04 (2006.01) 21.09.2016 Bulletin 2016/38 A61K 31/42 (2006.01) A61K 31/4427 (2006.01) A61P 11/06 (2006.01) A61P 35/00 (2006.01) (21) Application number: 10807045.9 (86) International application number: (22) Date of filing: 03.08.2010 PCT/US2010/044284 (87) International publication number: WO 2011/017350 (10.02.2011 Gazette 2011/06) (54) COMPOUNDS AS LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS VERBINDUNGEN ALS LYSOPHOSPHATIDSÄURE-REZEPTORANTAGONISTEN COMPOSÉS EN TANT QU’ANTAGONISTES DU RÉCEPTEUR DE L’ACIDE LYSOPHOSPHATIDIQUE (84) Designated Contracting States: (74) Representative: Reitstötter Kinzebach AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Patentanwälte GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Sternwartstrasse 4 PL PT RO SE SI SK SM TR 81679 München (DE) (30) Priority: 04.08.2009 US 231282 P (56) References cited: WO-A1-2004/031118 WO-A2-2009/011850 (43) Date of publication of application: US-A1- 2003 114 505 US-A1- 2006 194 850 13.06.2012 Bulletin 2012/24 • YAMAMOTO, T. ET AL.: ’Synthesis and (73) Proprietor: Amira Pharmaceuticals, Inc. evaluation of isoxazole derivatives as Princeton, NJ 08543 (US) lysophosphatidic acid (LPA) antagonists’ BIOORGANIC & MEDICINAL CHEMISTRY (72) Inventors: LETTERS vol. 17, 2007, pages 3736 - 3740, • HUTCHINSON, John, Howard XP022114572 San Diego • OHTA, H. ET AL.: ’Ki16425, a Subtype-Selective CA 92103 (US) Antoganist for EDG-Family Lysophosphatidic • SEIDERS, Thomas, Jon AcidReceptors’ MOLECULAR PHARMACOLOGY San Diego vol.
    [Show full text]