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RetatrutidStructure Imiterere ya
Inkomoko: PubChem |
Urukurikirane: YA⊃1; QGTFTSDYSI-L⊃2; LDKK⁴AQA⊃1; AFIEYLLEGGPSSGAPPPS⊃3; Inzira ya molekulari: C 221H 342N 46O.68 Uburemere bwa molekuline: 4731 g / mol Numero ya CAS: 2381089-83-2 PubChem CID: 171390338 Synonyme ： LY3437943 |
Research Retatrutid Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na Retatrutid?
Umubyibuho ukabije ni kimwe mu bibazo bikomeye by’ubuzima rusange muri iki gihe. Umubyibuho ukabije urashobora gukurura ibibazo bitandukanye byubuzima, nka diyabete yo mu bwoko bwa 2, indwara zifata umutima, hypertension, dyslipidemia, nindwara zumwijima zidafite inzoga. Hamwe n’ubwiyongere bukabije bw’umubyibuho ukabije, hagenda hakenerwa ubuvuzi bushya bushobora gucunga neza ibiro by’umubiri no kuzamura ubuzima [1] . Nubwo guhindura imibereho, nko kongera imyitozo ngororamubiri no kugabanya ibiryo, nuburyo bwibanze bwo gucunga ibiro, kubungabunga igihe kirekire kugabanya ibiro bikomeje kuba ingorabahizi kubantu benshi bakuze. Retatrutid nigitabo gishya cyakira reseptor agonist ikora kuri reseptor ya glucagon imeze nka peptide-1 (GLP-1R), reseptor ya glucose iterwa na insulineotropique polypeptide (GIPR), na reseptor ya glucagon (GCGR). Ubu buryo bwinshi-bwakirwa bwibikorwa butanga inyungu zidasanzwe mugutakaza ibiro. Ugereranije n’imiti igabanya ibiro ikora kuri reseptor imwe, Retatrutid irashobora kurushaho kugenzura imikorere yimikorere yumubiri [1] . Retatrutid igera ku kugabanya ibiro igenga imisemburo myinshi. Ntabwo igira ingaruka zikomeye zo kugabanya ibiro gusa ahubwo ifite n'ingaruka zoroheje zo munda. Mubyongeyeho, ugereranije nindi miti mishya yo kugabanya ibiro, Retatrutid, nka tronc reseptor agonist, ifite ingaruka zikomeye zo kugabanya ibiro hamwe nabantu benshi bakoreshwa.
Nubuhe buryo bwo gukora Retatrutid?
Uburyo bwibikorwa bya Retatrutid ahanini buturuka ku ngaruka zabwo za agonistic kuri reseptors nyinshi. Ubwa mbere, ingaruka za agonistic kuri reseptor ya glucagon isa na peptide-1 (GLP-1R) yongera imisemburo ya insuline, ikabuza gusohora glucagon, igabanya urugero rwa glucose mu maraso, kandi icyarimwe igatinda gusohora gastrica, ikongera guhaga, kandi igabanya gufata ibiryo [2] . Icya kabiri, ingaruka ziterwa na agonistic kuri reseptor ya glucose iterwa na glucose iterwa na glucose (GIPR) irashobora guteza imbere gusohora insuline, kongera ikoreshwa rya glucose, kandi bikagira ingaruka kuri metabolisme yibinure, bikabuza lipolysis no guteza imbere ibinure [2] . Byongeye kandi, nubwo ingaruka za Agonistic ya Retatrutid kuri reseptor ya glucagon (GCGR) ubusanzwe itera glycogenolysis na gluconeogenezi mu mwijima, ikongera urugero rwa glucose yamaraso, bitewe na Retatrutid, iyi ngaruka yo kongera glucose yamaraso ikurwaho ningaruka zabandi bakira. Muri icyo gihe, itera lipolysis kandi igabanya kwirundanya kw'amavuta [2] . Ubu buryo bwibikorwa byinshi birashobora kuba byiza mukuvura umubyibuho ukabije kuruta reseptor agonist.
Mugukora icyarimwe gukora ibyo byakira bitatu, Retatrutid irashobora gukora ingaruka zinyuranye zoguhindura metabolike kandi ikanatanga ingaruka zo kuvura umubyibuho ukabije nindwara zifitanye isano. Mu rwego rwo kugenzura urugero rwa glucose yamaraso, bitewe nogukora kwa GLP-1R na GIPR biteza imbere gusohora insuline no kubuza gusohora glucagon, hamwe no gukora GCGR bikarangizwa ningaruka zabandi bakira, Retatrutid irashobora kugenzura neza urugero glucose yamaraso, ifite akamaro kanini mukuvura diyabete yo mu bwoko bwa 2 [1, 2] . Mu rwego rwo kugabanya kwegeranya ibinure, gukora kwa GCGR bitera lipolysis no kugabanya ibinure. Muri icyo gihe, gukora kwa GLP-1R byongera guhaga no kugabanya gufata ibiryo, bikagabanya no guhuza ibinure [1, 2] . Byongeye kandi, Retatrutid nayo igira ingaruka nziza kuburwayi bwumwijima butarimo inzoga. Irashobora kugabanya ibinure biri mu mwijima no kunoza imikorere yumwijima. Ikigeragezo cyateganijwe, gihumye-impumyi, kigenzurwa na platbo cyerekanye ko impuzandengo ugereranije n’amavuta y’umwijima mu itsinda ry’ubuvuzi bwa Retatrutid mu byumweru 24 yari hasi cyane ugereranije n’ay'itsinda rya placebo [3].
HbA1c, uburemere bwumubiri, umuvuduko wamaraso, na lipide Data ni byibuze-kare bisobanura (hamwe nibibari byerekana SE) uhereye kubisesengura ryakozwe, keretse bivuzwe ukundi.
Inkomoko: PubMed [4]
Nigute Retatrutid igenga glucose metabolism nyuma yo gukora reseptors eshatu?
Retatrutid igenga glucose yamaraso ikoresheje uburyo bwinshi, harimo gukora GLP-1 na GIP yakira, gutera insuline gusohora, kubuza glucagon gusohora, gutinda gusohora gastrica, kugenzura metabolisme y’ibinure, no kugabanya urwego rwa ANGPTL3 / 8. Ku bijyanye no kugenzura amaraso glucose, Retatrutid ikora kuri reseptor ya GLP-1 na GIP, igateza imbere ubukangurambaga bwa selile pancreatic β selile ya glucose, guhuza no kurekura insuline, hanyuma igateza imbere gufata no gukoresha glucose mu mitsi, kugera ku ngaruka zo kugabanya glucose yamaraso [4, 5] .Mu bushakashatsi bwakozwe ku barwayi ba diyabete yo mu bwoko bwa 2, Retatrutid yerekanye ingaruka zikomeye zo kugabanya insimburangingo ya Hlogl. gusohora (Rosenstock J, 2023). Muri icyo gihe, gukora reseptor ya GLP-1 birashobora kubuza gusohora glucagon na selile pancreatic α selile, bikarinda glucose yamaraso kuba hejuru cyane. Mu bushakashatsi bw’ubuvuzi, byagaragaye ko urugero rwa glucagon rw’abarwayi bakoresha Retatrutid rwaragabanutse, ari nako rufasha gukomeza umutekano w’amaraso glucose [4, 5] . Gukora GLP-1 na reseptor ya GIP birashobora kandi gutinza umuvuduko wo gusiba gastrica, kugabanya igogorwa ryokunywa no gufata ibiryo, kandi bikagabanya izamuka rikabije ryamaraso ya glucose nyuma yinyuma. Ubushakashatsi bwerekanye ko igihe cyo gusiba gastrici y’abarwayi bavuwe na Retatrutid ari kirekire cyane nyuma yo kurya, bityo bikagabanya agaciro keza ka glucose yamaraso nyuma yo kubyara [4].
Kugena ibinure bya metabolisme na Retatrutid nabyo bigira ingaruka ku buryo butaziguye glucose metabolism. Kurugero, mubushakashatsi bwakozwe nabarwayi bafite umubyibuho ukabije, byagaragaye ko Retatrutid ishobora kugabanya urugero rwa triglyceride (TG), lipoprotein nkeya (LDL), hamwe na cholesterol ya lipoproteine (VLDL) nkeya cyane [2, 6] . Iri terambere rya metabolisme ya lipide rishobora kuba rifitanye isano no kunoza insuline, bityo bikagira uruhare mu kurwanya amaraso glucose. By'umwihariko, nyuma yo kuvura Retatrutid, plasma 3-hydroxybutyric aside (3-HB) iriyongera, iherekejwe no kwiyongera kwa 3-hydroxybutyrylcarnitine (C 4OH), igipimo cya acetylcarnitine na karnitine yubusa (C 2/ C 0), hamwe na acolycarnitine yinini yiyongera kuri aside ya adipose.
Retatrutid irashobora kandi kugabanya dihydroceramide yose (DhCers), kandi iri hinduka rifitanye isano no kunoza insuline, kugabanya indwara ya hepatike, hamwe no gutwika sisitemu [6] .Mu gihe kimwe, Retatrutid irashobora kandi kugabanya ubukana bw’ikigo cya ANGPTL3 / 8 muri serumu y’abarwayi ba diyabete mu bwoko bwa 2, bikagenga glucose metabolism . yo ANGPTL3 / 8 nuburyo bwiza bwo kuzenguruka bwa lipoprotein lipase (LPL), kandi urwego rwa serumu rufitanye isano itaziguye na TG hamwe na cholesterol ya lipoprotein nkeya (LDL-C). Retatrutid igabanya urwego rwa ANGPTL3 / 8, ishobora kugenga glucose metabolisme igabanya lipoproteine ikungahaye kuri triglyceride [7] .
Ni mu buhe buryo Retatrutid yerekana ingaruka zayo?
Ingaruka zikomeye zo kugabanya ibiro:
Retatrutid yerekanye ingaruka zikomeye zo kugabanya ibiro mubigeragezo byinshi byamavuriro. Kurugero, mubushakashatsi bwamavuriro burimo abantu bakuru 338 [2] , abarwayi bavuwe na dosiye zitandukanye za Retatrutid bagize ibiro byinshi mubyumweru 48. Muri bo, abarwayi bo mu itsinda rya 12mg dose bafite ibiro 24.2%, kandi umubare munini w'abarwayi wagabanutse ibiro ku buryo butandukanye. Kurugero, mubarwayi bahabwa dosiye ya 4mg, 8mg, na 12mg, 92%, 100%, na 100% byabarwayi batakaje 5% cyangwa birenga ibiro byumubiri. Mu bundi bushakashatsi [8] , ibigeragezo bibiri byateganijwe byitabiriwe n’abarwayi ba diyabete yo mu bwoko bwa 353 bwerekanye ko ugereranije na placebo, Retatrutid ishobora kugabanya cyane ibiro by’umubiri by’abarwayi ku gipimo cya 11.89 kandi ikagabanya na gemoglobine (HbA1C). Byongeye kandi, mu igeragezwa ry’abarwayi bakuze bafite umubyibuho ukabije utarwaye diyabete, Retatrutid yateje ibiro 24.2% ku barwayi, naho 83% by’abarwayi batakaje 15% cyangwa birenga ibiro by’umubiri mu byumweru 48. Ibisubizo byerekana ko Retatrutid ifite amahirwe menshi yo kugabanya ibiro.
Kuvura diyabete yo mu bwoko bwa 2 :
Retatrutid irerekana kandi ubushobozi bumwe na bumwe bwo kuvura diyabete yo mu bwoko bwa 2. Mu bigeragezo bimwe na bimwe by’amavuriro, Retatrutid yerekanye igabanuka rya glycated hemoglobine (HbA1c) hamwe no kugabanya ibiro biterwa no kugabanuka. Kurugero, mubushakashatsi bumwe, mubarwayi ba diyabete yo mu bwoko bwa 2, Retatrutid yerekanye ingaruka zikomeye zo kugenzura glucose yamaraso, kugabanya gemoglobine glycated 1,64% ugereranije na placebo [4, 8] . Byongeye kandi, mu igeragezwa ryateganijwe, rihumye-impumyi ebyiri, umwanya wawo, hamwe n’igenzurwa rikorwa-bigereranywa n’itsinda rya 2, icyitegererezo cy’inyamaswa zifite diyabete yo mu bwoko bwa 2 cyerekanye ko igabanuka rikabije ry’imisemburo ya gemoglobine ndetse no kugabanuka bitewe n’ibiro nyuma yo guhabwa imiti ya Retatrutid [4] . Ibi birashobora guterwa ningaruka zuzuye zibiyobyabwenge kuri GLP-1, GCGR, na GIPR, bitezimbere glucose metabolism hamwe nuburinganire bwingufu.
Gutezimbere ibintu bishobora gutera umutima-mitsi:
Retatrutid ntishobora kugabanya ibiro byumubiri gusa ahubwo inatezimbere ingaruka ziterwa numutima nimiyoboro yumutima, nka serumu lipid profil hamwe na glycated hemoglobine. Ibi byerekana isano iri hagati yumubyibuho ukabije nindwara zifata umutima, kandi Retatrutid irashobora guteza imbere ubuzima bwumutima nimiyoboro yabarwayi bafite umubyibuho ukabije binyuze munzira nyinshi. Kurugero, kugabanya urwego rutari HDL-C, apoB, na LDLP birashobora kugabanya ibyago byo kurwara aterosklerose; kugabanya urugero rwa glycated hemoglobine birashobora kunoza igenzura ryamaraso ya glucose kubarwayi ba diyabete, bityo bikagabanya ibyago byo kurwara umutima nimiyoboro y'amaraso [8-10] .
Kuvura indwara zumwijima zidafite inzoga (NAFLD):
Retatrutid ni igitabo gishya cya reseptor agonist peptide yibasira reseptor ya glucagon (GCGR), glucose-iterwa na insuline ya insuline ya polypeptide (GIPR), hamwe na glucagon imeze nka peptide-1 (GLP-1R). Ubushakashatsi bwerekanye ko Retatrutid ifite ubushobozi bwo kuvura indwara zumwijima zidafite inzoga. Mu bushakashatsi bumwe, ubushakashatsi bwateganijwe, buhumye-buhumyi, bugenzurwa na platbo bumara ibyumweru 48 bwakorewe ku bitabiriye amahugurwa bafite imikorere mibi ya metabolike idakira ifitanye isano n’indwara y’umwijima n’amavuta y’umwijima angana na 10%. Ibisubizo byagaragaje ko mu byumweru 24, impuzandengo y’amavuta y’umwijima ugereranije n’ibanze mu bitabiriye amahugurwa bavuwe na dosiye zitandukanye za Retatrutid (1mg, 4mg, 8mg, na 12mg) bari -42,9%, -57.0%, -81.4%, na -82.4%, mu gihe mu itsinda rya placebo bari + 0.3% [3] . Ibi byerekana ko Retatrutid ishobora kugira ingaruka zikomeye zo kuvura indwara zumwijima zidafite inzoga.
Mu gusoza, nkibintu bitatu byakira reseptor agonist, Retatrutid yerekana imbaraga nyinshi mukuvura umubyibuho ukabije nindwara zifitanye isano. Irashobora gukora reseptor ya glucagon, reseptor ya glucose iterwa na insulinotropique polypeptide, hamwe na reseptor ya glucagon imeze nka peptide-1, igenga byimazeyo metabolisme yumubiri kuva mubice byinshi, kunoza glucose yamaraso, kugabanya ibiro byumubiri, no kugenzura metabolisme ya lipide. Kugaragara kwa Retatrutid bizana uburyo bushya bwo kuvura abarwayi bafite umubyibuho ukabije, diyabete yo mu bwoko bwa 2, n'izindi ndwara. Biteganijwe ko izaca ku mbibi z’imiti gakondo ya reseptor agonist, itanga intwaro ikomeye yo gukemura ibibazo bikomeje gukomera by’umubyibuho ukabije n’indwara ziterwa na metabolike, guteza imbere iterambere ry’ubuvuzi bijyanye, kuzamura imibereho y’abarwayi, no kugabanya umutwaro w’ubuvuzi.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Rosenstock J ni intiti ikomeye cyane mubuvuzi, ikorana cyane ninzego nka kaminuza yubuvuzi ya kaminuza ya Texas Southwestern na kaminuza ya Texas Dallas. Akora kandi ubushakashatsi mubigo nka Centre ya VIGOR yo muri Kanada na Veloc Clin Res Ctr Med City. Ubushakashatsi bwe bwibanze kuri endocrinology na metabolism, sisitemu yumutima nimiyoboro yumutima na cardiologiya, farumasi, nubuvuzi bwikigereranyo, yibanda kuri diyabete, umubyibuho ukabije, hamwe nubuvuzi bujyanye no guteza imbere ibiyobyabwenge. J Rosenstock yageze ku ntera ishimishije mu buvuzi bw’amavuriro, yiswe Umushakashatsi wavuzwe cyane kuva 2017 kugeza 2024.Ibyo byerekana ingaruka zikomeye no kumenyekanisha ibikorwa bye. Binyuze ku bufatanye n’ibigo byinshi by’ubushakashatsi, yahinduye neza ibyavuye mu bushakashatsi mu bikorwa by’ubuvuzi, agirira akamaro abarwayi bafite indwara ziterwa na metabolike n’umutima ndetse no guteza imbere ubumenyi bw’ubuvuzi. Rosenstock J yashyizwe ku rutonde rwerekana [4].
