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Pseudoaspidin

$116

  • Brand : BIOFRON

  • Catalogue Number : BD-D1235

  • Specification : 95%(HPLC)

  • CAS number : 478-28-4

  • Formula : C25H32O8

  • Molecular Weight : 460.52

  • PUBCHEM ID : 5320755

  • Volume : 10MG

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Catalogue Number

BD-D1235

Analysis Method

HPLC,NMR,MS

Specification

95%(HPLC)

Storage

-20℃

Molecular Weight

460.52

Appearance

Powder

Botanical Source

Root sprouts of Agrimonia pilosa

Structure Type

Phenols

Category

SMILES

CCCC(=O)C1=C(C(=C(C(=C1O)CC2=C(C(=C(C(=C2O)C)OC)C(=O)CCC)O)O)C)OC

Synonyms

1-[3-[(3-butanoyl-2,6-dihydroxy-4-methoxy-5-methylphenyl)methyl]-2,4-dihydroxy-6-methoxy-5-methylphenyl]butan-1-one

IUPAC Name

1-[3-[(3-butanoyl-2,6-dihydroxy-4-methoxy-5-methylphenyl)methyl]-2,4-dihydroxy-6-methoxy-5-methylphenyl]butan-1-one

Applications

Density

Solubility

Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.

Flash Point

Boiling Point

Melting Point

InChl

InChI=1S/C25H32O8/c1-7-9-16(26)18-22(30)14(20(28)12(3)24(18)32-5)11-15-21(29)13(4)25(33-6)19(23(15)31)17(27)10-8-2/h28-31H,7-11H2,1-6H3

InChl Key

ASBDWVACJRRBIZ-UHFFFAOYSA-N

WGK Germany

RID/ADR

HS Code Reference

2938900000

Personal Projective Equipment

Correct Usage

For Reference Standard and R&D, Not for Human Use Directly.

Meta Tag

provides coniferyl ferulate(CAS#:478-28-4) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate

No Technical Documents Available For This Product.

PMID

28560067

Abstract

The aim of this study is to investigate the clinical significance of hypoxia inducible factor-1α (HIF-1α) expression in esophageal squamous cell cancer (ESCC) and clarify the effects of PX-478, a selective HIF-1α inhibitor, on ESCC both in vitro and in vivo. HIF-1α, cyclooxygenase-2 (COX-2) and programmed death ligand-1 (PD-L1) were markedly overexpressed in ESCC tissue and associated with poorer survival. In vitro, both COX-2 and PD-L1 expression of ESCC cells were significantly induced by CoCl2 treatment, but inhibited by HIF-1α knock-down or PX-478 treatment. Furthermore, PX-478 significantly inhibited tumor cell proliferation by inhibiting the G2/M transition and promoting apoptosis of ESCC cells. In addition, inhibited epithelial-mesenchymal transition was observed after PX-478 treatment. In vivo, PX-478 significantly decreased tumor volume following subcutaneous implantation. Together, our results indicated that PX-478 had significant antitumor activity against HIF-1α over-expressing ESCC tumors in vitro and in vivo. These results opened up the possibility of inhibiting HIF-1α for targeted therapy of ESCC.

KEYWORDS

Esophageal squamous cell cancer (ESCC), hypoxia inducible factor-1α (HIF-1α) inhibitors, PX-478, tumor growth, epithelial-mesenchymal transition (EMT)

Title

Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo

Author

Yingming Zhu,1,* Yuanwei Zang,2,* Fen Zhao,1 Zhenxiang Li,1 Jianbo Zhang,3 Liang Fang,2 Minghuan Li,1 Ligang Xing,1 Zhonghua Xu,2 and Jinming Yu1

Publish date

2017

Title

Proceedings of Reanimation 2017, the French Intensive Care Society International Congress

Author

Chtara Kamilia,corresponding author1 Kais Regaieg,2,3 Najeh Baccouch,2 Hedi Chelly,1 Mabrouk Bahloul,1 Mounir Bouaziz,1 Ali Jendoubi,corresponding author4 Ahmed Abbes,4 Houda Belhaouane,4 Oussama Nasri,4 Layla Jenzri,4 Salma Ghedira,5 Mohamed Houissa,5 Kamal Belkadi,corresponding author6 Youness Harti,6 Afak Nsiri,7,8 Khalid Khaleq,9,8 Driss Hamoudi,7 Rachid Harrar,7 Camille Thieffry,10 Frederic Wallet,11 Erika Parmentier-Decrucq,10 Raphaël Favory,10 Daniel Mathieu,10 Julien Poissy,corresponding author10 Thomas Lafon,12,13 Philippe Vignon,corresponding author14,15 Emmanuelle Begot,14 Alexandra Appert,16 Mathilde Hadj,16 Paul Claverie,16,17 Morgan Matt,18 Olivier Barraud,19 Bruno Francois,15 Amira Jamoussi,corresponding author20,21 Amira Ben Jazia,corresponding author20,22 Takoua Marhbene,20 Dhouha Lakhdhar,corresponding author20,23,24 Jalila Ben Khelil,20,21 Mohamed Besbes,20,21 Julien Goutay,corresponding author25 Caroline Blazejewski,26 Isabelle Joly-Durand,27 Isabelle Pirlet,28 Marie Pierre Weillaert,29 Sebastien Beague,26 Soufi Aziz,7 Reda Hafiane,corresponding author8 Khalid Hattabi,30 Mohamed Aziz Bouhouri,7,8 Driss Hammoudi,8 Abdelaziz Fadil,30 Rachid Al Harrar,8 Khalid Zerouali,31 Fatma Kaaniche Medhioub,corresponding author32 Rania Allela,33 Najla Ben Algia,34 Samar Cherif,35 Mohamed Taoufik Slaoui,corresponding author36 Souhail Boubia,37 Y. Hafiani,36 A. Khaoudi,36 R. Cherkab,36,38 W. Elallam,36 C. Elkettani,36,38 L. Barrou,36,38 M. Ridaii,37 Rihi El Mehdi,corresponding author39 Caroline Schimpf,40 Assaf Mizrahi,41 Benoît Pilmis,41 Alban Le Monnier,41 Kelly Tiercelet,40 Melanie Cherin,42 Cedric Bruel,40 Francois Philippart,corresponding author40 Sebastien Bailly,corresponding author43 Jc Lucet,44 Alain Lepape,45 Francois L’heriteau,46 Martine Aupee,47 Caroline Bervas,48 Sandrine Boussat,49 Anne Berger-Carbonne,50 Anaïs Machut,51 Anne Savey,52 Jean-Francois Timsit,53,54 REA‑RAISIN Study group, OUTCOMEREA study group, Keyvan Razazi,55 Jeremy Rosman,corresponding author55 Nicolas de Prost,55 Guillaume Carteaux,55 Chloe Jansen,56 Jean Winoc Decousser,57 Christian Brun-Buisson,55 Armand Mekontso Dessap,55 Aymen M’rad,corresponding author22 Zouhour Ouali,58 Manel Barghouth,22 Achille Kouatchet,corresponding author59 Rafael Mahieu,60 Emmanuel Weiss,61,62 David Schnell,63 Jean-Ralph Zahar,64 Margaux Artiguenave,65 Paktoris-Papine Sophie,65 Florence Espinasse,66 Faten El Sayed,67 Aurelien Dinh,68 Cyril Charron,65 Guillaume Geri,69 Antoine Vieillard-Baron,65 Xavier Repesse,corresponding author65 Hatem Kallel,corresponding author70 Claire Mayence,70 Stephanie Houcke,70 Pascal Guegueniat,70 Didier Hommel,70 Kaouther Dhifaoui,71 Zied Hajjej,corresponding author71 Amira Fatnassi,71 Walid Sellami,corresponding author71 Iheb Labbene,71 Mustapha Ferjani,71 Fahmi Dachraoui,corresponding author72 Sabrine Nakkaa,72 Abdelwaheb M’ghirbi,72 Ali Adhieb,72 Dhouha Ben Braiek,72 Kmar Hraiech,72 Ali Ousji,72 Islem Ouanes,72 Hammouda Zaineb,72 Saousen Ben Abdallah,72 Lamia Ouanes-Besbes,72 Fekri Abroug,72 Simon Klein,73 Matteo Miquet,73 Jean-Marc Thouret,73 Vincent Peigne,corresponding author73,74 Jean-Louis Daban,74 Mathieu Boutonnet,74 Bernard Lenoir,75 Takoua Merhbene,76 Celine Derreumaux,corresponding author77 Thierry Seguin,77 Jean-Marie Conil,77 Charlotte Kelway,corresponding author78 Valery Blasco,78 Cyril Nafati,78 Karim Harti,78 Laurent Reydellet,78 Jacques Albanese,78 Narjess Ben Aicha,79 Khaoula Meddeb,79 Ahmed Khedher,79 Jihene Ayachi,79 Nesrine Fraj,79 Nesrine Sma,79 Imed Chouchene,79 Mohamed Boussarsar,corresponding author80,81 Soumaya Ben Yedder,71 Walid Samoud,71 Bousselmi Radhouene,71 Bousselmi Mariem,71 Asma Ammar,82 Asma Ben Cheikh,82 Hend Ben Lakhal,22,79 Messaouda Khelfa,22,79 Yamina Hamdaoui,79 Nabiha Bouafia,82 Timothee Trampont,corresponding author17 Thomas Daix,15 Vincent Legarcon,17 Henri Hani Karam,17 Nicolas Pichon,14,15 Fatma Essafi,22 Nasreddine Foudhaili,22 Hafedh Thabet,83,84 Youssef Blel,corresponding author22 Nozha Brahmi,22 Hanane Ezzouine,corresponding author85 Mahmoud Kerrous,85 Saad El Haoui,85 Soufiane Ahdil,85 Abdellatif Benslama,85 Khalid Abidi,86 Tarek Dendane,86 Ssouni Oussama,86 Jihane Belayachi,87 Naoufal Madani,87 Redouane Abouqal,87 Amine Ali Zeggwagh,86 Hatem Ghadhoune,88 Anis Chaari,89 Guissouma Jihene,88 Hend Allouche,88 Insaf Trabelsi,88 Habib Brahmi,88 Mohamed Samet,88 Hatem El Ghord,88 Ben Sik Ali Habiba,90 Nouira Hajer,90 Najla Tilouch,90 Sondes Yaakoubi,90 Oussama Jaoued,90 Rim Gharbi,90 Mohamed Fekih Hassen,90 Souheil Elatrous,90 Julien Arcizet,91 Bertrand Leroy,91 Caroline Abdulmalack,92 Catherine Renzullo,91 Maël Hamet,92 Jean-Marc Doise,92 Jerôme Coutet,91 Chaigar Mohammed Cheikh,corresponding author85,93 Zakaria Quechar,85 Magalie Joris,corresponding author94 Dimitri Titeca Beauport,corresponding author94 Loay Kontar,94 Delphine Lebon,95 Berengere Gruson,95 Michel Slama,94 Jean-Pierre Marolleau,95 Julien Maizel,94 Julie Gorham,96 Lieveke Ameye,97 Thierry Berghmans,96 Marianne Paesmans,97 Jean-Paul Sculier,96 Anne-Pascale Meert,corresponding author96 Max Guillot,corresponding author98 Marie-Pierre Ledoux,99 Thierry Braun,98 Quentin Maestraggi,98,100 Baptiste Michard,98,101 Vincent Castelain,98,102 Raoul Herbrecht,99 Francis Schneider,98 Severine Couffin,corresponding author103 David Lobo,104 Nicolas Mongardon,69 Gilles Dhonneur,105 Roman Mounier,104 Pierrick Le Borgne,corresponding author106 Sophie Couraud,106 Jean-Etienne Herbrecht,98 Alexandra Boivin,98 Francois Lefebvre,107 Pascal Bilbault,106 Setti-Aouicha Zelmat,corresponding author108 Djamila-Djahida Batouche,corresponding author110 Fatima Mazour,111 Belkacem Chaffi,112 Nadia Benatta,113 Ali Habiba Sik,90 I. Talik,90 Maxime Perrier,114 Eliane Gouteix,114 Claude Koubi,114 Annabelle Escavy,114 Victoria Guilbaut,114 Jean-Philippe Fosse,corresponding author114 Rahma Ben Jazia,115 Ahmed Abdelghani,115 Pierre-Julien Cungi,corresponding author116 Julien Bordes,116 Cedric Nguyen,116 Candice Pierrou,117 Maximilien Cruc,116 Alain Benois,118 Frederic Duprez,corresponding author119 Thierry Bonus,119 Gregory Cuvelier,120 Sandra Ollieuz,119 Sharam Machayekhi,119 Frederic Paciorkowski,119 Gregory Reychler,121,122 Remi Coudroy,corresponding author123 Arnaud W. Thille,corresponding author123 Xavier Drouot,124 Veronique Diaz,124 Jean-Claude Meurice,125 Rene Robert,123 Olfa Turki,corresponding author1,126 Hmida Chokri Ben,1 Mona Assefi,corresponding author127 Romain Deransy,127 Helene Brisson,127 Antoine Monsel,127 Filomena Conti,128 Olivier Scatton,129 Olivier Langeron,127 Hassen Ben Ghezala,130 Salah Snouda,131 Chiekh Imen Ben,132 Moez Kaddour,131 Anwar Armel,corresponding author93,133 Lafrikh Youness,93 Bensaid Abdelhak,134 Miloudi Youssef,134 Al Harrar Najib,134 Amouzoun Mustapha,135 Mtioui Noufel,135 Zamd Mohamed,135 El Khayat Salma,135 Medkouri Ghizlane,135 Benghanam Mohamed,135 Ramdani Benyounes,135 Florent Montini,24 Sebastien Moschietto,24 Emilien Gregoire,136 Guillaume Claisse,137 Julien Guiot,138 Philippe Morimont,138 Jean-Marie Krzesinski,136 Christophe Mariat,139 Bernard Lambermont,138 Etienne Cavalier,140 Pierre Delanaye,corresponding author141 Soumia Benbernou,corresponding author142 Sofiane Ilies,142 Abdelkader Azza,143 Khalida Bouyacoub,144 Meriem Louail,109 Houria Mokhtari-Djebli,145 Romain Arrestier,corresponding author146 Fabrice Daviaud,146 Xavier Laborne Francois,147 Elsa Brocas,146 Gerald Choukroun,146 Oscar PeNuelas,148 Jose-Angel Lorente,148 Pablo Cardinal-Fernandez,148 Jose-Maria Rodriguez,149 Jose-Antonio Aramburu,149 Andres Esteban,148 Fernando Frutos-Vivar,148 Laurent Bitker,corresponding author150 Nicolas Costes,151 Didier Le Bars,151 Franck Lavenne,151 Mojgan Devouassoux,152 Jean-Christophe Richard,corresponding author150 Malika Mechati,corresponding author153,154 Marc Gainnier,153,155 Laurent Papazian,153,156,157 Christophe Guervilly,corresponding author153,156 Aude Garnero,corresponding author158 Jean Michel Arnal,158 Hadrien Roze,corresponding author159 Jean Christophe Richard,160 Benjamin Repusseau,159 Antoine Dewitte,159 Olivier Joannes-Boyau,159 Alexandre Ouattara,159 Nadia Harbouze,corresponding author38 A. M. Amine,38 A. G. Olandzobo,38 Alexandre Herbland,corresponding author161,162 Marie Richard,163 Nicolas Girard,162,164 Lucile Lambron,161 Olivier Lesieur,corresponding author161,162 Sarah Wainschtein,165 Sidonie Hubert,165 Albane Hugues,165 Marc Tran,40 Philippe Bouillard,162 Vlad Loteanu,162 Maxime Leloup,162 Alexandra Laurent,corresponding author166 Florent Lheureux,166 Alessia Prestifilippo,167 Martin Delgado Maria Cruz,168 Rigal Romain,169 Massimo Antonelli,170 Torra Lluis Blanch,168 Franck Bonnetain,171 Maria Grazzia-Bocci,168 Jordi Mancebo,172 Emmanuel Samain,173 Hebert Paul,169 Gilles Capellier,174 Taissa Zavgorodniaia,175 Marion Soichot,176 Isabelle Malissin,175,177 Sebastian Voicu,175,177 Pierre Garcon,175,177 Antoine Goury,corresponding author175,177 Lamia Kerdjana,175,177 Nicolas Deye,175,177 Emmanuel Bourgogne,176 Bruno Megarbane,corresponding author175,177,178 Olfa Mejri,22 Marwa Ben Hmida,22 Salma Tannous,179 Lucie Chevillard,179 Laurence Labat,179 Patricia Risede,179 Hana Fredj,22 Maxime Leger,corresponding author60 Marion Brunet,180 Gaël Le Roux,180 David Boels,180 Nicolas Lerolle,60 Souaad Farah,175 Helene Amiel-Niemann,181 Nathalie Kubis,181 Xavier Decleves,179 Nicoals Peyraux,182 Frederic Baud,corresponding author183 Micaela Serafini,182 Jean-Claude Alvarez,184 Annette Heinzelman,185 Mathieu Jozwiak,corresponding author186 Sandrine Millasseau,187 Jean-Louis Teboul,186 Jean-Emmanuel Alphonsine,186 Francois Depret,186 Nathalie Richard,187 Pierre Attal,188 Christian Richard,186,189 Xavier Monnet,186 Denis Chemla,190 Salma Jerbi,4 Wafa Khedhiri,4 Hatem Necib,4 Paolo Scarfo,corresponding author191 Charles Chevalier,192 Michael Piagnerelli,193 Alexandre Lafont,65 Antoine Galy,14 Claire Mancia,14 Amel Zerhouni,194 Kheira Tabeliouna,110 Ali Gaja,195 Bassem Hamrouni,5 Abir Malouch,4 Sami Fourati,4 Rihab Messaoud,4 Youssef Zarrouki,corresponding author196 Amra Ziadi,196 Manal Rhezali,196 Zahira Zouizra,197 Drissi Boumzebra,197 Mohamed Abdennasser Samkaoui,196 Jennifer Brunet,198 Bertrand Canoville,199 Pierre Verrier,198 Calin Ivascau,200 Amelie Seguin,199,201 Xavier Valette,199 Damien Du Cheyron,199 Cedric Daubin,corresponding author199 Wulfran Bougouin,corresponding author69,202 Nadia Aissaoui,203 Lionel Lamhaut,204 Daniel Jost,205 Carole Maupain,206 Frankie Beganton,207 Adrien Bougle,208 Florence Dumas,corresponding author209 Eloi Marijon,202 Xavier Jouven,210 Alain Cariou,69 Sudden Death Expertise Center, Florent Poirson,177 Ulriikka Chaput,211 Thomas Beeken,177 Leclerc Maxime,177 Oueslati Haikel,177 Dominique Vodovar,177 Jonathan Chelly,177 Philippe Marteau,211 Richard Chocron,212 Philippe Juvin,212 Thomas Loeb,213 Frederic Adnet,214 Eric Lecarpentier,215 Antoine Riviere,94 Bertand De Cagny,94 Thierry Soupison,94 Elodie Privat,corresponding author216 Josephine Escutnaire,217 Cyrielle Dumont,218 Valentine Baert,217 Christian Vilhelm,219 Herve Hubert,219 Stephane Leteurtre,220,221 Marion Fresco,corresponding author222 Michael Bubenheim,223 Gaetan Beduneau,224,225 Dorothee Carpentier,224,225 Steven Grange,224,225 Elise Artaud-Macari,224 Benoit Misset,222 Fabienne Tamion,224,225 Christophe Girault,224,225 Guillaume Dumas,corresponding author226 Sylvie Chevret,227 Virginie Lemiale,226 Djamel Mokart,228 Julien Mayaux,229,230,231 Frederic Pene,69 Martine Nyunga,232 Pierre Perez,233 Anne-Sophie Moreau,234,235,236 Fabrice Bruneel,237 Francois Vincent,238 Kada Klouche,239 Jean Reignier,240,241,242 Antoine Rabbat,243 Elie Azoulay,226 Jean-Pierre Frat,corresponding author123 Stephanie Ragot,244 Jean-Michel Constantin,245 Gwenael Prat,246 Alain Mercat,59 Thierry Boulain,247 Alexandre Demoule,corresponding author248,249 Jerôme Devaquet,250 Saad Nseir,251 Julien Charpentier,69 Laurent Argaud,252 Pascal Beuret,253 Jean-Damien Ricard,254 Christelle Teiten,255 Nicolas Marjanovic,256 Nicola Palamin,257 Erwan L’Her,corresponding author246 Arthur Bailly,240,258 Julie Boisrame-Helms,63,98,259,260 Benoit Champigneulle,261 Toufik Kamel,247 Emmanuelle Mercier,262 Aurelie Le Thuaut,263,264 Jean-Baptiste Lascarrou,corresponding author240,265 Amelie Rolle,corresponding author266 Audrey De Jong,corresponding author266 Gerald Chanques,266 Samir Jaber,266 Geoffroy Hariri,267 Jean-Luc Baudel,267 Vincent Dubee,267 Gabriel Preda,267 Simon Bourcier,267 Jeremie Joffre,268 Naïke Bige,267 Hafid Ait-Oufella,267 Eric Maury,corresponding author267 Houda Mater,90 Hamid Merdji,corresponding author69,269 David Grimaldi,69,270 Christophe Rousseau,269 Jean-Paul Mira,69,271 Jean-Daniel Chiche,corresponding author69 Ines Sedghiani,corresponding author272 A. Benabderrahim,272 Dhekra Hamdi,272 Asma Jendoubi,272 Mohamed Ali Cherif,272 Youssef Zied El Hechmi,272 Jerbi Zouheir,272 Francois Bagate,corresponding author55 Radhwen Bousselmi,71 Frederique Schortgen,corresponding author55 Pierre Asfar,273 Emmanuel Guerot,203 Grelon Fabien,274 Nadia Anguel,189 Lasocki Sigismond,275 Henry-Lagarrigue Matthieu,276 Frederic Gonzalez,277 Legay Francois,278 Christophe Guitton,279 Maleka Schenck,98 Doise Jean-Marc,280 Didier Dreyfuss,281,282 Peter Radermacher,283 for the HYPER2S Investigators and REVA research network, Antoine Frere,corresponding author265 Laurent Martin-Lefevre,265,284 Gwenhaël Colin,265 Maud Fiancette,265 Matthieu Henry-Laguarrigue,265 Jean-Claude Lacherade,265,284 Christine Lebert,240,265 Isabelle Vinatier,265 Aihem Yehia,265 Aurelie Joret,285 Nicolas Menunier-Beillard,286 Dalila Benzekri-Lefevre,287 Arnaud Desachy,288 Frederic Bellec,289 Gaëtan Plantefeve,290 Jean-Pierre Quenot,286,291 Ferhat Meziani,63 Elsa Tavernier,292 Stephan Ehrmann,285,293 Clinical Research in Intensive Care and Sepsis (CRICS network), Nicolas Chudeau,corresponding author294 Tommy Raveau,60 Valerie Moal,295 Pascal Houillier,296 Emmanuelle Rouve,corresponding author297 Karim Lakhal,298 Charlotte Salmon Gandonniere,293 Youenn Jouan,293 Laetitia Bodet-Contentin,293 Adrien Balmier,299 Jonathan Messika,corresponding author300 Cubrea network, Etienne De Montmollin,301 Victorine Pouyet,302 Benjamin Sztrymf,303 Abirami Thiagarajah,304 Damien Roux,corresponding author299 Marc Pineton De Chambrun,corresponding author305 Charles-Edouard Luyt,305,306 Francois Beloncle,307 Nathalie Zapella,237 Stanislas Ledochowsky,308 Nicolas Terzi,corresponding author309 Jean-Marc Mazou,310 Romain Sonneville,corresponding author54,311 Sylvie Paulus,corresponding author312 Yannick Fedun,313 Mickael Landais,corresponding author242 Jean-Herle Raphalen,314 Alain Combes,305,306 Zahir Amoura,315 Aemilia Jacquemin,corresponding author77 Felipe Guerrero,316 Bertrand Marcheix,317 Nicolas Hernandez,corresponding author77 Olivier Fourcade,318 Bernard Georges,77 Clement Delmas,319 Sarah Makoudi,corresponding author208 Audrey Genton,208 Remy Bernard,208 Guillaume Lebreton,320 Julien Amour,208 Charlotte Mazet,corresponding author321 Fanny Bounes,77 Gurbuz Murat,322 Laure Cronier,77 Guillaume Robin,77 Caroline Biendel,77 Stein Silva,323 Samia Boubeche,corresponding author324 Caroline Abriou,324 Veronique Wurtz,324 Vincent Scherrer,324 Nathalie Rey,324 Gioia Gastaldi,corresponding author224,325 Benoit Veber,326 Fabien Doguet,327 Arnaud Gay,327 Bertrand Dureuil,328 Emmanuel Besnier,324 Antoine Rouget,77 Guillaume Gantois,10 Eric Magalhaes,54 Ruben Wanono,329 Roland Smonig,54 Mathilde Lermuzeaux,54 Jordane Lebut,54 Andremont Olivier,54 Claire Dupuis,54 Aguila Radjou,54 Bruno Mourvillier,54,330 Mathilde Neuville,54 Marie Pia D’ortho,329 Lila Bouadma,54 Anny Rouvel-Tallec,329 Marika Rudler,corresponding author331 Nicolas Weiss,332 Vincent Perlbarg,333 Damien Galanaud,334 Dominique Thabut,335 Brain Liver Pitie-Salpêtriere Study Group (BLIPS), Emna Rachdi,corresponding author336 Ghada Mhamdi,337 Ahlem Trifi,336 Rim Abdelmalek,337 Sami Abdellatif,336 Foued Daly,336 Rochdi Nasri,336 Hanene Tiouiri,337 Salah Ben Lakhal,336 Geoffroy Rousseau,corresponding author338 Romain Asmolov,293 Leslie Grammatico-Guillon,339 Adrien Auvet,293 Said Laribi,338 Denis Garot,293 Pierre Francois Dequin,293 Antoine Guillon,293 Jean-Louis Ferge,corresponding author340 Gwenole Abgrall,340 Ronan Hinault,340 Shazima Vally,340 Benoit Roze,341 Agathe Chaplain,340 Cyrille Chabartier,340 Anne-Charlotte Savidan,340 Sabia Marie,340 Andre Cabie,341 Dabor Resiere,340 Ruddy Valentino,340 Hossein Mehdaoui,340 Lucas Benarous,corresponding author155,342 Marieme Soda-Diop,343 Fouad Bouzana,155 Gilles Perrin,153,155,456 Jeremy Bourenne,corresponding author153,155 Beatrice Eon,155 Dominique Lambert,155 Agnes Trebuchon,343 Geraldine Poncelet,corresponding author344 Fleur Le Bourgeois,345 Levy Michael,345 Guillot Camille,345 Jerôme Naudin,346 Anna Deho,346 Stephane Dauger,346 Michaël Sauthier,corresponding author347 Krystale Bergeron-Gallant,347 Guillaume Emeriaud,347 Philippe Jouvet,347 Nicolas Tiebergien,348 Matthias Jacquet-Lagreze,corresponding author348 Jean-Luc Fellahi,348 Florent Baudin,corresponding author349 Sandrine Essouri,347 Etienne Javouhey,350 Claude Guerin,351 Marie Lampin,corresponding author221 Ouardia Mamouri,352 Patrick Devos,353 Yasemin Karaca-Altintas,221 Matthieu Vinchon,354 David Brossier,corresponding author347 Redha Eltaani,347 Sonia Teyssedre,corresponding author355 Meyet Sabine,356 Jean-Christophe Bouchut,357 Olivier Peguet,357 Lucie Petitdemange,corresponding author358 Anne Sophie Guilbert,358 Nabil Tabet Aoul,359 Zakaria Addou,360 Nabil Aouffen,361 Benqqa Anas,93 Samira Kalouch,362 Khalid Yaqini,362 Aziz Chlilek,362 Rchi Abdou,93 Perrine Gravellier,363 Julie Chantreuil,corresponding author363 Nadine Travers,364 Antoine Listrat,364 Claire Le Reun,363 Geraldine Favrais,363 Zoe Coppere,corresponding author365 Stephane Blanot,366 Juliette Montmayeur,366 Regis Bronchard,367 Stephane Rolando,368 Gilles Orliaguet,366 Pierre-Louis Leger,corresponding author369 Jerôme Rambaud,369 Emilie Thueux,369 Alexandra De Larrard,369 Veronique Berthelot,369 Julien Denot,369 Marie Reymond,369 Alain Amblard,369 Sarah Morin-Zorman,corresponding author370 Etienne Lengline,371 Claire Pichereau,267 Eric Mariotte,372 Canet Emmanuel,373 Julien Poujade,corresponding author374 Guillaume Trumpff,corresponding author375 Ralf Janssen-Langenstein,98 Marie-Line Harlay,98 Noorah Zaid,105 Nawel Ait-Ammar,376 Christine Bonnal,376 Jean-Claude Merle,105 Francoise Botterel,376 Eric Levesque,corresponding author105 Zakaria Riad,corresponding author351 Mehdi Mezidi,351 Hodane Yonis,351 Mylene Aublanc,351 Sophie Perinel-Ragey,351 Floriane Lissonde,351 Aurore Louf-Durier,351 Romain Tapponnier,351 Bruno Louis,377 Jean-Marie Forel,156 Magali Bisbal,378 Samuel Lehingue,156 Romain Rambaud,156 Melanie Adda,156 Sami Hraiech,156 Elisa Marchi,156 Antoine Roch,156 Vincent Guerin,155 Sacha Rozencwajg,corresponding author306 Matthieu Schmidt,306 Guillaume Hekimian,306 Nicolas Brechot,corresponding author306 Jean Louis Trouillet,306 Sebastien Besset,306 Guillaume Franchineau,306 Ania Nieszkowska,306 Leprince Pascal,320 Maud Loiselle,corresponding author374 Chemam Sarah,379 Dangers Laurence,380 Thomas Guillemette,157 Alice Jacquens,299 Sebastien Kerever,381 Bertrand Guidet,267 Philippe Aegerter,382 Vincent Das,42 Muriel Fartoukh,383 Jan Hayon,384 Mathieu Desmard,385 Jean-Pierre Fulgencio,383 Benjamin Zuber,386 A. Soufi,7 K. Khaleq,7 D. Hamoudi,7 Charlotte Garret,corresponding author242 Matthieu Peron,387 Emmanuel Coron,387 Cedric Bretonniere,242 Etienne Audureau,388 Winters Audrey,389 Duvoux Christophe,390 Jacquelinet Christian,391 Azoulay Daniel,392 Feray Cyrille,390 Wissal Aissaoui,93 Kawtar Rghioui,93 Wafae Haddad,93 Houcine Barrou,93 Anna Carteaux-Taeib,393 Renato Lupinacci,393 Gilles Manceau,394 Florence Jeune,394 Christophe Tresallet,393 Sahar Habacha,395,396 Ines Fathallah,corresponding author395 Aymen Zoubli,395 Rafaa Aloui,395 Nadia Kouraichi,395 Emilie Jouet,corresponding author397 Julie Badin,397 Brice Fermier,397 Marc Feller,397 Mathieu Serie,397 Jerôme Pillot,corresponding author398 William Marie,398 Chloe Gisbert-Mora,398 Camille Vinclair,398 Pierre Lesbordes,398 Pascal Mathieu,398 Fabienne De Brabant,398 Emmanuel Muller,398 Marie-Aline Robaux,398 Mikhael Giabicani,corresponding author225,399 Antoine Marchalot,399 Stephanie Gelinotte,399 Pierre Louis Declercq,399 Jean-Pierre Eraldi,399 Francois Bougerol,399 Nicolas Meunier-Beillard,400 Herve Devilliers,401 Jean-Philippe Rigaud,399 Camille Verriere,165 Fanny Ardisson,corresponding author402 Nancy Kentish-Barnes,403 Gwenaëlle Jacq,237,404 Akli Chermak,405 Alexandre Lautrette,406 Matthieu Legrand,407 Alexis Soummer,408 Guillaume Thiery,409 Alice Cottereau,42 Emmanuel Canet,226 Marie Caujolle,corresponding author410 Jerôme Allyn,410 Dorothee Valance,410 Caroline Brulliard,410 Olivier Martinet,410 Julien Jabot,410 Thomas Gallas,410 David Vandroux,410 Nicolas Allou,410 Arthur Durand,corresponding author411 Remi Neviere,412 Florian Delguste,412 Eric Boulanger,412 Sebastien Preau,413 Ruste Martin,351 Helene Cochet,corresponding author414 Jean Pierre Ponthus,414 Virginie Amilien,414 Martial Tchir,414 Elise Barsam,414 Mohsen Ayoub,414 Jean Francois Georger,414 Izaute Guillame,415 Julie Assaraf,corresponding author416 Simona Tripon,417 Maxime Mallet,418 Guilaume Barbara,419 Guillaume Louis,420 Stephane Gaudry,300 Nicolas Barbarot,421 Angeline Jamet,123 Herve Outin,422 Sebastien Gibot,419 Pierre-Edouard Bollaert,corresponding author419 Mathilde Holleville,corresponding author237 Stephane Legriel,237 Anne Laure Chateauneuf,237 Sebastien Cavelot,237 Jean-Denis Moyer,237 Jean Pierre Bedos,237 Philippe Merle,423 Aurelie Laine,corresponding author424 De Sa Natalie,425 Mathieu Cornuault,corresponding author426 Jerome Libot,426 Karim Asehnoune,427 Bertrand Rozec,258 Jacques Dantal,428 Michel Videcoq,426 Thecle Degroote,corresponding author251 Emmanuelle Jaillette,251 Farid Zerimech,429 Balduyck Malika,429 Jean-Francois Llitjos,corresponding author69,269 Marlene Amara,430 Guillaume Lacave,237 Beatrice Pangon,430 Jose Mavinga,corresponding author431 Joseph Nsiala Makunza,432 M. E. Mafuta,433 Yves Yanga,431 Amisi Eric,431 Jp Ilunga,431 Ma Kilembe,431 Fanny Alby-Laurent,269 Julie Toubiana,269 Amel Mokline,corresponding author434 Achraf Laajili,434 Helmi Amri,434 Imene Rahmani,434 Nidhal Mensi,434 Lazheri Gharsallah,434 Sofiene Tlaili,434 Bahija Gasri,434 Rym Hammouda,434 Amen Allah Messadi,434 Pierre-Antoine Allain,62 Nathallie Gault,435 Catherine Paugam-Burtz,62 Arnaud Foucrier,corresponding author62 Bassem Chatbri,396 Yousra Bourbiaa,436 Lamia Thabet,436 Arthur Neuschwander,corresponding author437 Looten Vincent,438 Jennifer Beck,439 Chhor Vibol,437 Yavchitz Amelie,437 Matthieu Resche-Rigon,438 Jean MantzRomain Pirracchio,437 Côme Bureau,corresponding author249 Maxens Decavele,249 Sebastien Campion,440 Roukia Ainsouya,440 Marie-Cecile Nierat,440 Helene Prodanovic,230 Mathieu Raux,441 Thomas Similowski,249,231 Bruno-Pierre Dube,231 Suela Demiri,231 Martin Dres,231 Faten May,corresponding author55 Herve Quintard,442 Ilias Kounis,443 Faouzi Saliba,corresponding author443 Stephane Andre,443 Marc Boudon,443 Philippe Ichai,443 Aline Younes,443 Lionel Nakad,443 Audrey Coilly,443 Teresa Antonini,443 Rodolphe Sobesky,443 Eleonora De Martin,443 Didier Samuel,443 Noemie Hubert,444 Mai-Anh Nay,247 Johann Auchabie,60 Bruno Giraudeau,445 Reignier Jean,242 Michaël Darmon,corresponding author446 Stephane Ruckly,447 Maïte Garrouste-Orgeas,448 Elisabeth Gratia,309 Dany Goldgran-Toledano,449 Samir Jamali,450 Anne Sylvie Dumenil,451 Carole Schwebel,452 Laurent Brisard,corresponding author258 Philippe Bizouarn,258 Thierry Lepoivre,258 Johanna Nicolet,258 Jean Christophe Rigal,258 Jean Christian Roussel,453 Cherifa Cheurfa,454 Julien Abily,224 Thomas Lescot,455 Isaline Page,457 Stephanie Warnier,457 Monique Nys,457 Anne-Francoise Rousseau,457 Pierre Damas,corresponding author457 Fabrice Uhel,458 Mathieu Lesouhaitier,458 Murielle Gregoire,459 Baptiste Gaudriot,460 Arnaud Gacouin,458 Yves Le Tulzo,458 Erwan Flecher,461 Karin Tarte,462 Jean-Marc Tadie,corresponding author458 Quentin Georges,446 M. Soares,463 Kyeongman Jeon,464 Sandra Oeyen,465 Chin Kook Rhee,466 Pascale Gruber,467 Marlies Ostermann,468 Quentin Hill,469 Peter Depuydt,470 Christelle Ferra,471 Alice Muller,472 Bourmaud Aurelie,473 Christopher Niles,10 Fabien Herbert,474 Sylviane Pied,474 Severine Loridant,475 Nadine Francois,475 Anne Bignon,476 Boualem Sendid,477 Caroline Lemaitre,225 Celine Dupre,corresponding author236 Aymen Zayene,corresponding author234 Lucie Portier,478 Nathalie De Freitas Caires,478 Philippe Lassalle,479 Aymeric Le Neindre,corresponding author480 Pascal Selot,480 Daniel Ferreiro,480 Maria Bonarek,480 Stepahen Henriot,480 Julie Rodriguez,480 Mara Taddei,corresponding author481 Mauro Di Bari,482 Cheryl Hickmann,corresponding author481 Diego Castanares-Zapatero,483 Louise Deldicque,484 Peter Van Den Bergh,485 Gilles Caty,486 Jean Roeseler,483,487 Marc Francaux,484 Pierre-Francois Laterre,483,487 Bastien Dupuis,120 Sharam Machayeckhi,488 Celine Sarfati,corresponding author489 Alex Moore,489 Paula Mendialdua,489 Emilie Rodet,489 Catherine Pilorge,490 Francois Stephan,490 Saida Rezaiguia-Delclaux,490 Jonathan Dugernier,corresponding author487 Michel Hesse,491 Thibaud Jumetz,487 Emilie Bialais,487 Virginie Depoortere,491 Jean Bernard Michotte,492 Xavier Wittebole,487 and Francois Jamar493

Publish date

2017

PMID

25476790

Abstract

Background
Dihydroartemisinin (DHA) is a component of artemisinin-based combination therapy (ACT), which is widely recommended for treatment of uncomplicated falciparum malaria. DHA is also the main metabolite of artemether and artesunate, both of which are used in ACT. Due to auto-induction metabolism, declining plasma concentrations after the repeated dosing have been reported for artemisinin (Qing-hao-su) and artemether. This study was designed to evaluate the potential auto-induction metabolism of DHA in healthy Chinese adults after multiple oral doses of DHA. The polymorphic effects of UGT1A9 (I399C>T) and UGT2B7*2 (802C>T), the major enzymes involved in the metabolism of DHA, on the pharmacokinetic profiles of DHA and its metabolite was also studied.

Methods
Sixteen healthy Chinese subjects (four I399TT/802CC, four I399CC/802TT, four I399TT/802TT and four I399CT/802CT) received four recommended oral doses of Artekin, an ACT containing DHA (80 mg/dose) and piperaquine (PQ; 640 mg/dose), at 0, 6, 24 and 32 h. Plasma samples were analysed for DHA and its metabolite using a validated liquid chromatography tandem mass spectrometric (LC-MS) method.

Results
DHA and its glucuronidated metabolite DHA-Glu were detected in human plasma after oral administration of DHA-PQ. Compared with the first dose, the AUC0-t of the parent drug DHA decreased significantly (P<0.01) with increased oral clearance (CL/F) after each repeated dose of DHA-PQ, whereas its metabolite DHA-Glu did not change (P>0.05) in AUC0-t or Cmax. The phase II metabolic capability, calculated by the AUC0-t ratio of DHA-Glu to the parent drug DHA, increased 1.5-fold (90% CI, 1.3-1.7), 1.2-fold (90% CI, 1.1-1.3) and 1.7-fold (90% CI, 1.5-1.8) after the second, third and fourth dose, respectively. No polymorphic effect was found for UGT1A9 (I399C>T) and UGT2B7*2 (802C>T) on the pharmacokinetic profiles of DHA and its metabolite DHA-Glu.

Conclusions
The auto-induction phase II metabolism of DHA was present in healthy Chinese subjects after the recommended two-day oral doses of DHA-PQ (Artekin). The metabolic capability could recover after a 12-h dosing interval, which suggested that the alternative common three-day regimen (once daily) for DHA-PQ could probably lead to higher bioavailability of DHA. The polymorphism of UGT1A9 (I399C>T) and UGT2B7*2 (802C>T) may not be a concern during the treatment with DHA.

Electronic supplementary material
The online version of this article (doi:10.1186/1475-2875-13-478) contains supplementary material, which is available to authorized users.

KEYWORDS

Dihydroartemisinin, Auto-induction metabolism, Healthy Chinese, UGTs, Polymorphism

Title

The effect of UGTs polymorphism on the auto-induction phase II metabolism-mediated pharmacokinetics of dihydroartemisinin in healthy Chinese subjects after oral administration of a fixed combination of dihydroartemisinin-piperaquine

Author

Meitong Zang, Fanping Zhu, Lixia Zhao, Aijuan Yang, Xinxiu Li, Huixiang Liu, and Jie Xingcorresponding author

Publish date

2014