I-Retatrutide yinoveli ye-peptide yokwenziwa eyilelwe ukuba ngaxeshanye isebenze ezintathu ezamkeli ezingundoqo ezibandakanyekayo kwi-glucose homeostasis kunye nokulungelelana kwamandla: iglucagon receptor (GCGR), i-glucose exhomekeke kwi-insulinotropic polypeptide receptor (GIPR) kunye ne-glucagon-like peptide-1 receptor (GLP- 1R) (Finan et al., 2023, The New England Journal of Medicine).Ngokujolisa ezi receptor, i-retatrutide ilinganisa imiphumo ye-endogenous ligands, iglucagon, GIP kunye ne-GLP-1, ezizihomoni ezilawula i-glucose metabolism kunye nobunzima bomzimba kwizicubu ezahlukeneyo, ezifana ne-pancreas, isibindi, ingqondo, izicubu ze-adipose kunye nesisu. iphecana (Drucker, 2023, Nature).
Ngokungafaniyo ne-endogenous ligands, enesiqingatha sobomi obufutshane, ukuthotywa ngokukhawuleza kwe-dipeptidyl peptidase-4 (DPP-4) enzyme kunye nemiphumo engafunekiyo, efana ne-hypoglycemia kunye nesicaphucaphu (Drucker, 2023, Nature), i-retatrutide yenziwe ukuba yoyise ezi zinto. imida.I-Retatrutide yi-peptide edityanisiweyo eyenziwe ngolandelelwano olulungisiweyo lweglucagon oludityaniswe kulandelelwano olulungisiweyo lwe-GLP-1 ngolandelelwano lwe-GIP (Finan et al., 2023, The New England Journal of Medicine).Uhlengahlengiso lubandakanya ukutshintshwa kwe-amino acid kunye nokususwa okuphucula ukuzinza, amandla kunye nokukhetha kwepeptide ye-receptors ezintathu (Finan et al., 2023, I-New England Journal of Medicine).
I-Retatrutide ibonise iipropati eziphawulekayo ze-pharmacological kunye nokusebenza konyango ekutyebeni kunye nohlobo lwe-2 yeswekile kwizifundo zangaphambili kunye neklinikhi.Kwimizekelo yezilwanyana zokukhuluphala kunye nesifo sikashukela, i-retatrutide ibonise iziphumo eziphezulu ekunciphiseni amanqanaba e-glucose yegazi, ukuvuselela i-insulin secretion, ukucinezela i-glucagon secretion, ukulibazisa ukukhupha isisu, ukunciphisa ukutya kunye nobunzima bomzimba xa kuthelekiswa ne-agonists enye okanye ezimbini ze-receptors ezintathu (Gault et. al., 2023, isifo seswekile, ukutyeba kakhulu kunye ne-Metabolism; Coskun et al., 2023a, i-Molecular Metabolism).I-Retatrutide iye yaphucula iprofayili ye-lipid, umsebenzi wesibindi, ukuvuvukala kunye neeparamitha ze-cardiovascular kwezi zilwanyana (Gault et al., 2023, Isifo seswekile, ukukhuluphala kunye ne-Metabolism; Coskun et al., 2023a, i-Molecular Metabolism).
Kulingo lwezonyango lwabantu, i-retatrutide ikwabonise iziphumo ezithembisayo kwizigulana ezityebileyo kunye neswekile.I-Retatrutide yayinyanyezelwe kakuhle kwaye ibonise iziphumo ezixhomekeke kwidosi ekunciphiseni amanqanaba e-glucose yegazi, ukuvuselela ukukhutshwa kwe-insulin, ukucinezela i-glucagon secretion kunye nokunciphisa ukutya kwisigaba soku-1 esibandakanya amavolontiya anempilo kunye nezigulane ezinesifo seswekile se-2 (Coskun et al., 2023b, i-Diabetes Care Care). ).I-Retatrutide efunyenwe ukuya kuthi ga kwi-17.5% ithetha ukunciphisa ubunzima kwiiveki ze-24 xa kuthelekiswa ne-placebo kwisigaba se-2 sokufunda esibandakanya izigulane ezinokukhuluphala kunye nokugqithisa.Le lahleko yobunzima ihamba kunye nokuphuculwa kolawulo lwe-glycemic, iphrofayili ye-lipid, ukusebenza kwesibindi kunye nomgangatho wobomi (iziphumo ze-Lilly zesigaba se-2 retatrutide ezipapashwe kwi-New England Journal of Medicine zibonisa ukuba i-molecule yophando iphumelele ukuya kwi-17.5% ithetha ukunciphisa ubunzima kwiiveki ze-24 abantu abadala abatyebileyo kunye nokutyeba kakhulu., 2023).I-Retatrutide nayo yayineprofayili ekhuselekileyo yokhuseleko ngaphandle kweziganeko ezimbi kakhulu okanye iziganeko ze-hypoglycemia ezixeliweyo.
Umzobo 1. I-Retatrutide (LY3437943) inqanda i-glycated hemoglobin A1c (HbA1c) ixabiso (A) kunye nobunzima bomzimba (B) ngexesha.
(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, inoveli kathathu ye-GIP, GLP-1, kunye I-glucagon receptor agonist kubantu abanesifo seswekile se-2: isigaba 1b, i-multicentre, i-double-blind, i-placebo-controlled, i-randomized, i-multiple-acending doses trial.Lancet.
I-Retatrutide okwangoku iphantsi kophuhliso ngu-Eli Lilly kunye neNkampani njengomviwa omtsha weyeza lokutyeba kunye nohlobo lwe-2 yeswekile.Imele indlela entsha ekujoliswe kuyo kwii-receptors ezininzi ezibandakanyekayo kwi-glucose metabolism kunye nokulinganisela kwamandla kunye ne-molecule enye.I-Retatrutide ibonise ukusebenza okuphawulekayo kwiimodeli zezilwanyana kunye nezilingo zabantu ngokhuseleko olufanelekileyo kunye neeprofayili zokunyamezela.Uphononongo olongezelelweyo luyafuneka ukuze kuqinisekiswe iingenelo zayo zexesha elide kunye nemingcipheko enokubakho kubantu abakhulu nabahlukeneyo.I-Retatrutide inokunika ukhetho olutsha kwizigulana ezinengxaki yokutyeba kunye nesifo seswekile kwaye zidinga unyango olusebenzayo ngakumbi.
Singumenzi wepolypeptide eTshayina, esineminyaka eliqela yamava aqolileyo kwimveliso yepolypeptide.I-Hangzhou Taijia Biotech Co., Ltd. yingcali yomenzi we-polypeptide ekrwada, enokubonelela amashumi amawaka ezinto ezikrwada ze-polypeptide kwaye inokwenziwa ngokweemfuno.Umgangatho weemveliso ze-polypeptide ugqwesileyo, kwaye ukucoceka kunokufikelela kwi-98%, eye yaqatshelwa ngabasebenzisi emhlabeni wonke.
