I-Retatrutide iyinoveli yokwenziwa kwe-peptide eklanyelwe ukwenza kusebenze ama-receptors amathathu abalulekile ngesikhathi esisodwa abandakanyeka ku-glucose homeostasis kanye nebhalansi yamandla: i-glucagon receptor (GCGR), i-insulinotropic polypeptide receptor (GIPR) encike kuglucose (GIPR) kanye ne-glucagon-like peptide-1 receptor (GLP- 1R) (Finan et al., 2023, The New England Journal of Medicine).Ngokuqondisa kulawa ma-receptors, i-retatrutide ilingisa imiphumela yama-endogenous ligands, iglucagon, GIP kanye ne-GLP-1, okungamahomoni alawula i-glucose metabolism nesisindo somzimba ezicutshini ezihlukahlukene, ezifana namanyikwe, isibindi, ubuchopho, izicubu ze-adipose kanye nesisu. ipheshana (Drucker, 2023, Imvelo).
Ngokungafani nama-endogenous ligands, ane-half-life emfushane, ukuwohloka okusheshayo yi-enzyme dipeptidyl peptidase-4 (DPP-4) kanye nemiphumela emibi engathandeki, efana ne-hypoglycemia kanye nesicanucanu (Drucker, 2023, Nature), i-retatrutide yakhelwe ukunqoba lezi. ukulinganiselwa.I-Retatrutide iyi-peptide ehlanganisiwe eyakhiwe ngokulandelana kweglucagon eguquliwe exhunywe ngokulandelana kwe-GLP-1 eguquliwe ngokulandelana kwe-GIP (Finan et al., 2023, The New England Journal of Medicine).Ukuguqulwa kufaka phakathi ukushintshwa kwe-amino acid kanye nokususwa okuthuthukisa ukuzinza, amandla kanye nokukhetha kwe-peptide kuma-receptors amathathu (Finan et al., 2023, The New England Journal of Medicine).
I-Retatrutide ibonise izakhiwo eziphawulekayo zemithi kanye nempumelelo yokwelapha ekukhuluphaleni kanye nohlobo lwesifo sikashukela sohlobo 2 ezifundweni zangaphambi komtholampilo nezomtholampilo.Ezimodeli zezilwane zokukhuluphala kanye nesifo sikashukela, i-retatrutide ibonise imiphumela ephakeme ekwehliseni amazinga kashukela egazini, ivuselela ukukhiqizwa kwe-insulin, icindezele ukukhishwa kwe-glucagon, ukubambezeleka kokukhipha isisu, ukunciphisa ukudla kanye nesisindo somzimba uma kuqhathaniswa ne-agonists eyodwa noma ezimbili zama-receptors amathathu (Gault et. al., 2023, Isifo sikashukela, Ukukhuluphala kanye ne-Metabolism; Coskun et al., 2023a, I-Molecular Metabolism).I-Retatrutide iphinde yathuthukisa iphrofayili ye-lipid, ukusebenza kwesibindi, ukuvuvukala kanye nemingcele yenhliziyo nemithambo yegazi kulezi zilwane (Gault et al., 2023, Diabetes, Obesity and Metabolism; Coskun et al., 2023a, Molecular Metabolism).
Ezivivinyweni zomtholampilo zabantu, i-retatrutide nayo ibonise imiphumela ethembisayo ezigulini ezikhuluphele kanye neziguli ezinesifo sikashukela.I-Retatrutide yabekezelelwa kahle futhi yabonisa imiphumela encike kumthamo ekwehliseni amazinga kashukela egazini, ivuselela ukukhiqizwa kwe-insulin, icindezela ukukhishwa kweglucagon kanye nokunciphisa isifiso sokudla ocwaningweni lwesigaba 1 olubandakanya amavolontiya anempilo kanye neziguli ezinesifo sikashukela sohlobo 2 (Coskun et al., 2023b, Ukunakekelwa Kwesifo sikashukela ).I-Retatrutide efinyelelwe kufika ku-17.5% isho ukuncishiswa kwesisindo emavikini angu-24 uma kuqhathaniswa ne-placebo ocwaningweni lwesigaba 2 olubandakanya iziguli ezinokukhuluphala nokukhuluphala ngokweqile.Lokhu kuncipha kwesisindo kwakuhambisana nokuthuthukiswa kokulawulwa kwe-glycemic, iphrofayili ye-lipid, ukusebenza kwesibindi kanye nekhwalithi yokuphila (imiphumela ye-Retatrutide yesigaba sesi-2 sika-Lilly eshicilelwe ku-New England Journal of Medicine ibonisa i-molecule yophenyo efinyelelwe ku-17.5% isho ukunciphisa isisindo emavikini angu-24 abantu abadala abanokukhuluphala nokukhuluphala ngokweqile., 2023).I-Retatrutide nayo ibe nephrofayili yokuphepha evumayo ngaphandle kwezehlakalo ezimbi kakhulu noma iziqephu ze-hypoglycemia ezibikiwe.
Umfanekiso 1. I-Retatrutide (LY3437943) ivimbela inani le-glycated hemoglobin A1c (HbA1c) (A) nesisindo somzimba (B) ngokuhamba kwesikhathi.
(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 ephindwe kathathu ye-GIP, GLP-1, kanye i-glucagon receptor agonist kubantu abanesifo sikashukela sohlobo 2: isigaba 1b, i-multicentre, impumputhe kabili, i-placebo-controlled, randomised, multiple-acending dose trial. Lancet. 2022 Nov 26;400(10366):1869-1881.)
I-Retatrutide okwamanje isathuthukiswa ngu-Eli Lilly and Company njengekhandidethi elisha lesidakamizwa sokukhuluphala kanye nesifo sikashukela sohlobo 2.Imele indlela entsha yokukhomba ama-receptors amaningi abandakanyeka ku-glucose metabolism kanye nebhalansi yamandla nge-molecule eyodwa.I-Retatrutide ibonise ukusebenza kahle okuphawulekayo kumamodeli ezilwane kanye nokuhlolwa kwabantu ngokuphepha okuhle nokubekezelelana kwamaphrofayela.Kudingeka ucwaningo olwengeziwe ukuze kuqinisekiswe izinzuzo zayo zesikhathi eside kanye nezingozi ezingaba khona kubantu abakhulu nabahlukahlukene kakhulu.I-Retatrutide ingase inikeze inketho entsha ezigulini ezinenkinga yokukhuluphala nesifo sikashukela futhi ezidinga ukwelashwa okusebenzayo.
Singumkhiqizi we-polypeptide e-China, esineminyaka eminingana yokuhlangenwe nakho okuvuthiwe ekukhiqizeni i-polypeptide.I-Hangzhou Taijia Biotech Co., Ltd. ingumkhiqizi wezinto ezingavuthiwe ze-polypeptide, enganikeza amashumi ezinkulungwane zezinto zokusetshenziswa ze-polypeptide futhi ingenziwa ngokwezifiso ngokwezidingo.Izinga lemikhiqizo ye-polypeptide lihle kakhulu, futhi ubumsulwa bungafinyelela ku-98%, okuye kwaqashelwa abasebenzisi emhlabeni wonke.Siyakwamukela ukuthi uxhumane nathi.
