Retatrutide ndi novel synthetic peptide yomwe idapangidwa kuti nthawi imodzi iyambitse zolandilira zitatu zazikulu zomwe zimakhudzidwa ndi glucose homeostasis ndi mphamvu yokwanira: glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR) ndi glucagon-like peptide-1 receptor (GLP- 1R) (Finan et al., 2023, The New England Journal of Medicine).Poyang'ana ma receptor awa, retatrutide imatsanzira zotsatira za endogenous ligands, glucagon, GIP ndi GLP-1, omwe ndi mahomoni omwe amayang'anira kagayidwe ka shuga ndi kulemera kwa thupi m'magulu osiyanasiyana, monga kapamba, chiwindi, ubongo, minofu ya adipose ndi m'mimba. thirakiti (Drucker, 2023, Nature).
Mosiyana ndi ma endo native ligands, omwe amakhala ndi theka la moyo wautali, kuwonongeka mwachangu ndi dipeptidyl peptidase-4 (DPP-4) enzyme ndi zotsatira zoyipa, monga hypoglycemia ndi nseru (Drucker, 2023, Nature), retatrutide idapangidwa kuti igonjetse izi. malire.Retatrutide ndi peptide yophatikizika yopangidwa ndi glucagon yosinthidwa yolumikizidwa ndi kusinthidwa kwa GLP-1 motsatana ndi GIP (Finan et al., 2023, The New England Journal of Medicine).Zosinthazi zikuphatikiza m'malo mwa amino acid ndikuchotsa zomwe zimathandizira kukhazikika, potency ndi kusankha kwa peptide pama receptors atatu (Finan et al., 2023, The New England Journal of Medicine).
Retatrutide yawonetsa zinthu zochititsa chidwi zachipatala komanso chithandizo chamankhwala mu kunenepa kwambiri komanso mtundu wa 2 shuga m'maphunziro azachipatala komanso azachipatala.M'zinyama za kunenepa kwambiri ndi matenda a shuga, retatrutide yawonetsa zotsatira zabwino kwambiri pakuchepetsa kuchuluka kwa shuga m'magazi, kulimbikitsa katulutsidwe ka insulin, kupondereza katulutsidwe ka glucagon, kuchedwetsa kutulutsa m'mimba, kuchepetsa kudya komanso kulemera kwa thupi poyerekeza ndi ma agonist amodzi kapena awiri a ma receptor atatu (Gault et. al., 2023, Diabetes, Kunenepa Kwambiri ndi Metabolism; Coskun et al., 2023a, Molecular Metabolism).Retatrutide yathandiziranso mbiri ya lipid, ntchito ya chiwindi, kutupa ndi magawo amtima mu nyama izi (Gault et al., 2023, Diabetes, Obesity and Metabolism; Coskun et al., 2023a, Molecular Metabolism).
M'mayesero azachipatala a anthu, retatrutide yawonetsanso zotsatira zabwino mwa odwala onenepa kwambiri komanso odwala matenda ashuga.Retatrutide idalekerera bwino ndipo idawonetsa zotsatira zodalira mlingo pakutsitsa shuga m'magazi, kulimbikitsa katulutsidwe ka insulin, kupondereza katulutsidwe ka glucagon komanso kuchepetsa chilakolako chofuna kudya mu gawo 1 la kafukufuku wokhudza odzipereka athanzi komanso odwala omwe ali ndi matenda amtundu wa 2 (Coskun et al., 2023b, Diabetes Care Care). ).Retatrutide yomwe imapezeka mpaka 17.5% imatanthauza kuchepetsa kulemera kwa masabata a 24 poyerekeza ndi placebo mu gawo lachiwiri la kafukufuku wokhudza odwala kunenepa kwambiri komanso onenepa kwambiri.Kuonda kumeneku kunatsagana ndi kuwongolera kwa glycemic control, mbiri ya lipid, magwiridwe antchito a chiwindi ndi moyo wabwino (zotsatira za Lilly's phase 2 retatrutide zofalitsidwa mu The New England Journal of Medicine zikuwonetsa kuti molekyulu yofufuzira yomwe idakwaniritsidwa mpaka 17.5% imatanthauza kuchepetsa thupi pakatha milungu 24 akuluakulu omwe ali ndi kunenepa kwambiri komanso onenepa kwambiri., 2023).Retatrutide inalinso ndi mbiri yabwino yachitetezo popanda zovuta zazikulu kapena zochitika za hypoglycemia.
Chithunzi 1. Retatrutide (LY3437943) imalepheretsa glycated hemoglobin A1c (HbA1c) mtengo (A) ndi kulemera kwa thupi (B) pakapita nthawi.
(Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, Haupt A, Benson CT, Hernandez-Illas M, D'Alessio DA, Milicevic Z. LY3437943, novel triple GIP, GLP-1, ndi glucagon receptor agonist mwa anthu omwe ali ndi matenda a shuga amtundu wa 2: gawo 1b, multicentre, akhungu awiri, placebo-controlled, randomised, multiple-acending dose trial. Lancet.
Retatrutide pano ikupangidwa ndi Eli Lilly and Company ngati mankhwala atsopano a matenda a kunenepa kwambiri komanso mtundu wa 2 shuga.Imayimira njira yatsopano yolondolera ma receptor angapo omwe amakhudzidwa ndi kagayidwe ka glucose ndi mphamvu yamagetsi ndi molekyu imodzi.Retatrutide yawonetsa bwino kwambiri pazitsanzo za nyama ndi mayesero a anthu okhala ndi mbiri yabwino yotetezedwa komanso yolekerera.Maphunziro owonjezera akufunika kuti atsimikizire ubwino wake wautali komanso zoopsa zomwe zingakhalepo m'magulu akuluakulu komanso osiyanasiyana.Retatrutide ikhoza kupereka njira yatsopano kwa odwala omwe akulimbana ndi kunenepa kwambiri komanso matenda a shuga ndipo amafunikira chithandizo chamankhwala chothandiza kwambiri.
Ndife opanga ma polypeptide ku China, omwe ali ndi zaka zingapo okhwima pakupanga polypeptide.Hangzhou Taijia Biotech Co., Ltd. ndi katswiri wopanga polypeptide yaiwisi, yomwe imatha kupereka makumi masauzande azinthu zopangira polypeptide ndipo imathanso kusinthidwa malinga ndi zosowa.Ubwino wa zinthu za polypeptide ndi zabwino kwambiri, ndipo chiyero chimatha kufika 98%, chomwe chadziwika ndi ogwiritsa ntchito padziko lonse lapansi.
