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Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Kodi Elafibranor (GFT505) ndi chiyani?

Elafibranor (GFT505) ufa (923978-27-2), ndi mankhwala oyesera omwe kafukufuku wawo akupitilizabe. Makamaka, kuphunzira kwake ndi chitukuko cha Genfit zimadalira luso la Zamgululi (GFT505) ufa (923978-27-2) polimbana ndi matenda monga matenda osokoneza bongo a mafuta osokoneza bongo, dyslipidemia, insulin, ndi matenda ashuga.

Elafibranor (GFT505) kachitidwe kogwirira ntchito

Elafibranor (GFT505) ufa ndi mankhwala amkamwa omwe amagwira ntchito pazinthu zitatu za PPAR. Amaphatikizapo PPARa, PPARd, ndi PPARg. Komabe, imagwira ntchito makamaka pa PPARa.

Makina a Elafibranor amachita ndi ovuta chifukwa amasankha mosiyanasiyana mapangidwe a cofactor ku receptor ya nyukiliya. Zotsatira zake, izi zimatsogolera pakuwongolera mitundu ya majini komanso zotsatira zachilengedwe.

Elafibranor (GFT505) ufa umatha kuzindikira ndikuwonetsa ntchito yosankha ma nyukiliya receptor modulator (SNuRMs). Zotsatira zake, imawongolera magwiridwe antchito limodzi ndi zovuta zomwe zimachepetsedwa.

Ma molekyulu onse okhala ndi ma multimodal and pluripotent atsimikizira kukhala othandiza pomenya nkhondo zosiyanasiyana. Zimaphatikizapo kukana insulini komanso matenda a shuga, kutupa, kunenepa kwambiri, ndi lipid triad, zomwe zimadziwika ndi kuwonjezeka kwa cholesterol ya HDL komanso kutsitsa cholesterol ya LDL ndi triglycerides.

Kusiyana pakati pa kachitidwe ka Elafibranor kagwiritsidwe ntchito ndi kamakina kena kamene kamayang'ana ma PPAR ku NASH (nonalcoholic steatohepatitis) ndikuti sikuwonetsa zochitika za PPARy za pharmacological.

Zotsatira zake, Elafibranor ogwiritsa ntchito samakumana ndi zovuta zosafunikira zomwe zimalumikizidwa ndi PPARy activation. Zotsatira zoyipa izi zimaphatikizapo; kusungidwa kwa madzimadzi, edema, ndi kulemera kwake zimapeza zonse zomwe zimakulitsa chiopsezo cha munthu kuvutika ndi mtima.

Elafibranor (GFT505) Phunziro la mankhwala a Nash

NASH (nonalcoholic steatohepatitis) ndimatenda a chiwindi omwe amabweretsa kutupa ndi kuwonongeka kwa ma hepatocytes komanso kudzikundikira kwamafuta omwe amadziwikanso kuti lipid m'malo am'madzi. Nthawi zambiri, mikhalidwe ina yathanzi monga metabolic syndrome, matenda a shuga a 2, komanso kunenepa kwambiri ndizomwe zimayambitsa matenda osokoneza bongo a nonalcoholic steatohepatitis (NASH), komanso matenda osagwiritsa ntchito mafuta a chiwindi osagwirizana ndi mowa.

Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Masiku ano, anthu ambiri akudwala matenda oyambawa. Gawo lowopsa pa izi ndikuti lingayambitse matenda a cirrhosis, chikhalidwe chomwe chimapangitsa chiwindi kuti chisagwire ntchito. Imathanso kupita ku khansa ya chiwindi ndipo nthawi zina, imayambitsa imfa.

Nkhani zomvetsa chisoni za NASH (nonalcoholic steatohepatitis) ndikuti sizimatenga zaka zambiri ndikupitilizabe kukhudza aliyense. Choyipa chachikulu ndikuti matendawa amatha kukhala asymptomatic, ndipo wina sangadziwe kuti akuvutika ndi matendawa mpaka atakula pang'ono.

Kuwonongeka ndi kutupa komwe kumabwera ndi NASH (sanali mowa steatohepatitis) zitha kuchititsanso matenda amtima ndi m'mapapo. Ndi anthu ambiri tsopano omwe akuvutika ndi vutoli lomwe limachokera ku matenda a chiwindi osakhudzana ndi zakumwa zoledzeretsa, ofufuza akufunafuna njira zina zochiritsira zina kuwonjezera pa kufalikira kwa chiwindi.

Chimodzi mwa mankhwala omwe akuphunziridwa chithandizo cha NASH ndi Elafibranor (GFT505) ufa (923978-27-2). Pakadali pano, zikuwonetsa kuti zimayambitsa zotsatirapo ziwiri zazikulu zamatendawa, mwachitsanzo, kudziyambitsa magazi ndi kutupa. Kukongola komwe kuli nako ndikuti ndikololera kwambiri ndipo sikangapangitse munthu kuvutika ndi zovuta zina. Ndiye chifukwa chake bungwe la US Food and Drug Administration lipereka mwachangu dzina ili Chithandizo cha NASH.

Pakadali pano, Elafibranor (GFT505) ufa ali mkuyesa kwachipatala kwa Gawo 3, wotchedwanso kuti KUGONJETSA IT.

SEMBANI-IT

Ndi kafukufuku wapadziko lonse yemwe adayamba mu kotala yoyamba ya 2016, yomwe idasinthidwa mosasinthika, yoyesedwa ndi placebo 2: 1 komanso osawona kawiri. Odwala omwe akukhudzidwa ndi phunziroli ndi omwe ali ndi vuto la NASH (NAS> = 4) ndi fibrosis (F2 kapena F3 pomwe kuwonongeka kwa chiwindi kumadziwika kale. Mu phunziroli, odwalawo atha kuperekedwa ndi Mlingo wa Elafibranor (GFT505) 120mg kapena placebo kamodzi tsiku lililonse.

Odwala okwanira chikwi chimodzi omwe adalembetsedwa amathandizira kuwonetsa ngati NASH ichiritsidwa ndi Elafibranor (GFT505) popanda kuipira microsis poyerekeza ndi omwe amathandizidwa ndi placebo.

Gulu loyamba lidalembetsedwera mu Epulo 2018, ndipo kuwunikira kwa zotsatirazi kunanenedwa kumapeto kwa chaka cha 2019. Zomwe zalembedwazi zikufotokozera ngati Elafibranor avomerezedwa ndi US Food and Drug Administration ngati angapeze chilolezo cha European Medicines Agency, chabwino imadziwika kuti EMA pofika 2020.

Kafukufukuyu adapita patsogolo mu Disembala 2018 pomwe Data Safety Monitoring Board (DSMB) idatsimikiza kupitilira kwa mlandu popanda kusintha kulikonse. Izi zidachitika ataganizira zomwe zidakonzedweratu pamasamba otetezedwa atatha miyezi makumi atatu.

Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Zotsatira za preclinic komanso maphunziro azachipatala pamankhwala a NASH

Kuchita bwino ndi chitetezo chaElafibranor pamankhwala a NASH adawunikiridwa kale m'mbuyomu kudzera m'mitundu yambiri yamatenda. Gawo 5a 2a, mayesero osiyanasiyana anachitika osiyanasiyana anthu odwala matenda a metabolic. Zinaphatikizanso omwe ali ndi matenda ashuga a 2 kapena matenda ashuga wachiwiri ndi atherogenic dyslipidemia. Phunziroli, zinaonedwa kuti Elafibranor amalimbikitsa;

  • Kuchepetsa chiopsezo chazovuta zamtima
  • Kuchepetsa zolemba za kuvulala kwa chiwindi
  • Anti-yotupa katundu
  • Kuchuluka kwa insulin
  • Glucose homeostasis
  • Makonda a lipid.

Yesero la 2b lomwe linayambitsidwa mu 2012 linali loyesa kwambiri komanso kafukufuku woyamba wapadziko lonse lapansi kuchitidwa ku NASH. Apa ndipamene Elafibranor adapeza FDA yomwe idalimbikitsa kuti "Bungwe la NASH lisamayende bwino ndi Fibrosis." Awo anali chiyembekezo chachikulu choyeserera gawo 3 padziko lonse lapansi chomwe chikuchitikabe.

Zinaonedwa kuti odwala omwe adalandira chithandizo cha NASH ndi Elafibranor adawona kusintha kwa zilembo zosagwira ntchito za chiwindi monga ALP, GGT, ndi ALT. Mwakuwunika kwa malembedwe apakati, panali kuwunika kuti Elafibranor (GFT505) Mlingo wa 120mg unapereka zotsatira zachiwopsezo cha ziwopsezo za mtima ndi zochitika za NASH, Zimaphatikizapo;

  • Zotsutsa-zotupa
  • Kusintha kwa insulin sensitivity ndi glucose metabolism mwa odwala omwe ali ndi matenda ashuga
  • Sinthani milingo ya lipoprotein ndi ma lipids a plasma.
Mphamvu ya Elafibranor pochiza ana a NASH

Mlingo womwe ana akuvutika ndi kunenepa kwambiri ukuwonjezeka kwambiri, zomwe zimapangitsa kukhala ndi nkhawa yayikulu yazaumoyo. Mu kafukufuku omwe adachitika mu 2016, zidawonedwa kuti NAFLD(nonal ya mowa wamafuta chiwindi) imakhudza pafupifupi 10-20% ya ana. Zinawonetseranso kuti NAFLD ya ana ndi yomwe ingakhale yoyambira kwambiri yakulephera kwa chiwindi, matenda a chiwindi, komanso kukhazikika kwa chiwindi mwa ana ndi achinyamata.

Mu Januwale 2018 panali kukhazikitsidwa kwapadera kwa pulogalamu ya ana ya NASH akudziwa kuti Elafibranor ndiye mankhwala okhawo omwe atsimikizira kuti amagwira ntchito mu chithandizo cha NASH mwa akulu ndipo ali pachiwopsezo chothandizira ana.

Kodi Elafibranor angagwiritsidwe ntchito limodzi ndi mankhwala ena mu chithandizo cha NASH?

Zadziwika kale kuti Elafibranor imagwira ntchito pa chithandizo cha NASH ikagwiritsidwa ntchito payekha. Komabe, chifukwa cha zovuta za matendawa, zitha kugwiritsidwa ntchito limodzi ndi mankhwala ena poyang'anira chiwindi, NASH, komanso kutsutsana kwa matendawa.

Elafibranor (GFT505) ntchito zina

Mu mankhwala a cholstasis

Cholestasis ndi mkhalidwe womwe umayambitsidwa ndi kuwonongeka kwa mapangidwe a bile ndikuyenda kwake kudzera ndulu ndi duodenum. Zitha kuthandizira kukulira kwa matenda a chiwindi ndi matenda a chiwindi, kulephera kwa chiwindi, komanso ngakhale kufunikira kwa kupatsirana kwa chiwindi. Kafukufuku wazachipatala omwe adachitika adawonetsa kuti Elafibranor (GFT505) ufa amachepetsa zolemba zam'magazi mu plasma motero zimatsimikizira kuti zingakhale zothandiza pothandizira matenda a cholestasis.

shuga

Matenda a shuga ndi vuto lomwe limayamba chifukwa chokhala ndi shuga wambiri kapena shuga m'magazi. Zimakhudza anthu pafupifupi mamiliyoni anayi padziko lonse lapansi. Mmodzi amakhala ndi mtundu wachiwiri wa matenda ashuga ngati thupi lawo silitha kutulutsa ndi kugwiritsa ntchito bwino insulin.

Kafukufuku wachitika pa elafibranor akuwonetsa kuti amachepetsa kupitilira kwa matenda a shuga a mtundu wachiwiri m'njira ziwiri. Yoyamba kudzera pakusintha kwa glucose metabolism m'thupi.

Amathandizanso kudziwa za insulin m'misempha ndi m'ziphuphu.

Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Kutsiliza

Phunziro la Elafibranor limabwera ngati nkhani yabwino kwa aliyense amene akuvutika ndi NASH. Popeza taperekedwa kwa odwala oposa mazana asanu ndi atatu mpaka pano ndikuwonetsa kuti ndizothandiza, tikuyembekeza kuti anthu sadzafunikiranso kuikidwa chiwindi.

Panalibe Elafibranor mogwirizana ndi mankhwala wapezeka ndi sitagliptin, simvastatin, kapena warfarin, zomwe zikusonyeza kuti zitha kugwiritsidwa ntchito limodzi ndi mankhwala ena bwinobwino. Elafibranor amaloledwa bwino mthupi ndipo samawonetsa zovuta zilizonse.

Zothandizira

  1. Njira Zotanthauzira Zotanthauzira mu Diabetes, Obesity, and Nonalcoholic Fatty, zolembedwa ndi Andrew J. Krentz, Christian Weyer, Marcus Hompesch, Springer Nature, tsamba 261
  2. Ma PPAR mu Cellular and - Whole Body Energy Metabolism osinthidwa ndi Walter Wahli, Rachel Tee, 457-470
  3. Kunenepa kwambiri ndi Gastroenterology, Nkhani ya Gastroenterology Clinic ya Kumpoto, Octavia Pickett-Blakely, Linda A. Lee, tsamba 1414-1420

Zamkatimu

2019-07-23 zowonjezera
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