|
1kits （10Ibikoresho）
| Umubare: | |
|---|---|
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?
Ubushakashatsi bwakozwe na Retatrutid bufitanye isano rya bugufi n’ibibazo bikomeje kwiyongera ku isi by’umubyibuho ukabije na diyabete, ndetse n’imipaka y’imiti isanzwe ivura: umubyibuho ukabije na diyabete bibangamira ubuzima rusange bw’abaturage, aho umubare w’abatuye umubyibuho ukabije ku isi uteganijwe kugera kuri miliyari 4.005 mu 2035 kandi umubare w’abarwayi ba diyabete ukiyongera ukagera kuri miliyoni 592. Peptide nyinshi zakira reseptor agonist peptide yagaragaye nkigisubizo, gishobora gukumira umubyibuho ukabije, kuvura diyabete, no kwirinda ingaruka ziterwa nuburozi bwibiyobyabwenge bihari, bigatuma biba inzira yo guteza imbere umubyibuho ukabije na diabete.
Nubuhe buryo bwo gukora Retatrutid?
Kugenzura ingufu za metabolisme binyuze mumikorere myinshi-yakira
Retatrutid ni reseptor tronc agonist yibasira glucose iterwa na insulineotropique polypeptide reseptor (GIPR), glucagon imeze nka peptide-1 reseptor (GLP-1R), hamwe na glucagon reseptor (GCGR). Irakora icyarimwe ikora reseptors eshatu, igenga ingufu za metabolisme binyuze munzira nyinshi.
Igikorwa cya GIPR agonist:
GIP ni imisemburo yo mu mara isohora insuline isohora ingirabuzimafatizo K yo mu mara ikarekurwa nyuma yo kurya. Retatrutid ikora GIPR, igatera gusohora insuline, ikongerera insuline, bityo igafasha umubiri kurushaho gufata neza no gukoresha glucose, bityo bikagabanya urugero rwa glucose yamaraso. Byongeye kandi, GIP irashobora guhindura metabolisme yibinure muguhindura imikorere ya adipocyte no kugabanya ibinure [1].
GLP-1R ibikorwa bya agonist:
GLP-1 ni imisemburo ya peptide isohoka mu ngirabuzimafatizo L. Nyuma yo gukora GLP-1R, Retatrutid itanga ingaruka zitandukanye zingirakamaro. Irashobora gutera insuline gusohora muburyo bwa glucose bushingiye ku kwibanda, bityo bikagabanya urugero rwisukari mu maraso. Irashobora gutinza ubusa gastrica, kongera guhaga, no kugabanya ibiryo. Agonism ya GLP-1R irashobora kandi gukora kuri sisitemu yo hagati yo hagati, igenga ubushake bwo kurya no kuringaniza ingufu, bityo igafasha kugabanya ibiro [2].
Ingaruka za GCGR agonist:
Glucagon isanzwe yongera glucose yamaraso, ariko bitewe na Retatrutid, agonism ya GCGR itanga ingaruka zitandukanye. Itera glycogenolysis na gluconeogenezi mu mwijima. Ingaruka ziterwa na Retatrutid, umubiri ntiwiyongera muburyo bworoshye bwamaraso ya glucose ahubwo ugenga metabolisme yingufu kugirango wongere ibinure, bityo ugabanye ibiro kandi uhindure metabolism. Agonism ya GCGR irashobora kandi kugira ingaruka kuri metabolisme ya hepatike, kugabanya ibinure bya hepatike [3].
Ingaruka kuri Metabolism Bifitanye isano na Physiologique Inzira
Mugukorera icyarimwe gukora kuri reseptors eshatu zavuzwe haruguru, Retatrutid igira ingaruka nyinshi muburyo bwa metabolism bijyanye na physiologique.
Amaraso ya glucose:
Mugukoresha GIPR na GLP-1R kugirango uteze imbere gusohora insuline, no kugenzura neza GCGR, Retatrutid irashobora kugabanya urugero rwa glucose yamaraso. Ingaruka ya hypoglycemic igaragara iyo glucose yamaraso izamutse, mugihe bidashoboka gutera hypoglycemia mugihe glucose yamaraso ari ibisanzwe, ifasha mugukumira glucose yamaraso kubarwayi ba diyabete [4].
Gucunga ibiro:
Retatrutid yerekana imikorere ikomeye mugucunga ibiro. Mugukoresha GLP-1R, itinda gusiba gastric, ikongera guhaga, kandi igabanya ibiryo; muguhindura metabolisme yibinure, itera kugabanuka kwamavuta no gukoresha ingufu, bityo bikagabanuka. Igeragezwa rya Clinical ryerekanye ko abarwayi bafite umubyibuho ukabije cyangwa ufite ibiro byinshi bavuwe na Retatrutid bagabanuka cyane mu gihe runaka [5,6].
Amabwiriza ya Lipid:
Kuvura retatrutid biteza imbere imyirondoro yabarwayi. Igabanya triglyceride (TG), cholesterol ya lipoprotein nkeya (LDL-C), hamwe na cholesterol ya lipoprotein nkeya cyane (VLDL-C), mu gihe kandi igenga apolipoproteine, nko kugabanya apolipoproteine B (apoB) hamwe na apolipoproteine C -III (apoC). atherosklerose no guteza imbere ubuzima bw'umutima n'imitsi [7].
Kunoza metabolisme ya hepatike:
Ku barwayi bafite indwara y’umwijima idafite inzoga (NAFLD) ifitanye isano n’imikorere mibi ya metabolike, Retatrutid igabanya cyane ibinure byumwijima. Mu bigeragezo bijyanye n'amavuriro, abarwayi bavuwe bafite dosiye zitandukanye za Retatrutid bagaragaje igabanuka rikabije ry'amavuta y'umwijima ugereranije n'ibanze, byerekana ko Retatrutid igira ingaruka nziza ku mikorere y'amavuta y'umwijima, ifasha mu kunoza imikorere y'umwijima [3].
Igishushanyo 1 Uburyo bwa Retatrutid bwibikorwa [8].
Ni ubuhe buryo bukoreshwa muri Retatrutid?
Kuvura umubyibuho ukabije:
Umubyibuho ukabije wabaye ikibazo gikomeye cy’ubuzima rusange ku isi, gifitanye isano rya hafi no gutangira no gutera indwara zitandukanye zidakira. Retatrutid yerekanye akamaro gakomeye mukuvura umubyibuho ukabije. Abarwayi bafite umubyibuho ukabije bavuwe na Retatrutid bagize igabanuka rikabije ry'uburemere bw'umubiri. Mu byumweru 48 icyiciro cya 2 cy’umubyibuho ukabije, abarwayi bavuwe na 8mg na 12mg za Retatrutid bagabanutse ibiro 22.8% na 24.2%. Mu kindi cyiciro cya 2 gihumye-gihumye, cyateganijwe, kigenzurwa na platbo, abarwayi bo mumatsinda atandukanye ya dose bahuye nuburemere butandukanye bwibiro mubyumweru 24 nibyumweru 48. Itsinda rya 12mg ryageze ku gutakaza ibiro 24.2% mu byumweru 48, mugihe itsinda rya placebo ryabonye gusa kugabanuka -2.1%. Retatrutid igabanya neza uburemere bwumubiri kubarwayi bafite umubyibuho ukabije, itanga igikoresho gishya kandi gikomeye cyo kuvura umubyibuho ukabije. Ubuvuzi bwa Retatrutid kububyibushye ntibugabanya ibiro byumubiri gusa ahubwo bushobora no kunoza ibindi bibazo byubuzima bifitanye isano numubyibuho ukabije, nko kugabanya imihangayiko iterwa no kugabanya ibimenyetso byindwara ziterwa n'umubyibuho ukabije binyuze mu kugabanya ibiro; kugabanya ibiro birashobora kandi gufasha kunoza ibibazo biterwa n'umubyibuho ukabije nko gusinzira apnea [3,6].
Ubwoko bwa 2 bwo kuvura diyabete:
Indwara ya diyabete yo mu bwoko bwa 2 ni indwara idakira ya metabolike idakira irangwa no kurwanya insuline no gusohora kwa insuline bidahagije. Retatrutid ifite agaciro gashoboka mukuvura diyabete yo mu bwoko bwa 2. Itera imisemburo ya insuline ikora reseptor ya GLP-1, igahindura insuline, kandi ikagabanya urugero rwa glucose. Ingaruka zayo zigabanya ibiro nazo zifasha kunoza imiterere yabarwayi ba diyabete yo mu bwoko bwa 2, kubera ko umubyibuho ukabije ari ikintu cyingenzi gishobora gutera diyabete yo mu bwoko bwa 2, kandi kugabanya ibiro bishobora kongera insuline, bikanafasha mu kugenzura amaraso glucose. Mu bushakashatsi bwakorewe ku barwayi barwaye diyabete yo mu bwoko bwa 2, Retatrutid yatumye ibiro bigabanuka cyane ndetse no kugabanuka ku buryo bugaragara urugero rwa hemoglobine A1c (HbA1c), HbA1c yagabanutseho 1,64% ugereranije na placebo. Ibi byerekana ko Retatrutid itagenzura gusa urugero rwa glucose yamaraso ahubwo inatezimbere muri rusange abarwayi bafite diyabete yo mu bwoko bwa 2 hakoreshejwe uburyo bwinshi, harimo no kugabanya ibiro, bityo bikazamura imibereho yabo [6].
Indwara y'umwijima idafite inzoga (NAFLD):
NAFLD ni imvune ziterwa n'umwijima ziterwa n'umwijima zifitanye isano rya bugufi no kurwanya insuline no kwandura indwara, bikubiyemo ibintu bitandukanye birimo umwijima w'amavuta utarimo inzoga, umwijima udafite inzoga, na cirrhose. Retatrutid yerekana ubushobozi butanga ubuvuzi bwa NAFLD. Mu igeragezwa ryateganijwe, rihumye-rihumye, rigenzurwa na platbo ryitabiriwe n’abitabiriye bafite indwara ziterwa n’umwijima ziterwa n’umwijima hamwe n’ibinure by’umwijima ≥10%, mu byumweru 24, impinduka zigereranijwe zijyanye n’ibinure by’umwijima bivuye ku murongo w’ibanze byari bitandukanye cyane mu matsinda ya Retatrutid: -81.4% mu itsinda rya 8mg, -82.4% mu itsinda rya 12 mg, na + 0.3% mu itsinda rya placebo. Ibi byerekana ko Retatrutid ishobora kugabanya neza ibinure byumwijima, bifite akamaro kanini mugutezimbere indwara yumwijima yabarwayi ba NAFLD. Ifite amasezerano nkuburyo bushya bwo kuvura NAFLD, bishobora kudindiza iterambere ryindwara no kugabanya ibyago byingaruka zikomeye nka cirrhose [3].
Umwanzuro
Retatrutid yerekana imbaraga zitanga icyizere cyo kuzamura imiterere y’umwijima y’abarwayi ba NAFLD, ikora binyuze mu buryo bwinshi burimo kugenzura ingufu za metabolisme, kunoza insuline, ingaruka zo kurwanya inflammatory, no guhindura metabolisme ya lipide.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Rosenstock, J ni intiti idasanzwe ifite umwuga ufitanye isano n’ibigo byinshi bizwi, harimo ikigo cy’ubuvuzi cya kaminuza ya Texas y’amajyepfo y’iburengerazuba, kaminuza ya Texas Dallas, n’ikigo cya VIGOR cyo muri Kanada. Ubushakashatsi bwe bukubiyemo ibintu byinshi nka Endocrinology & Metabolism, Rusange & Imbere mu Gihugu, Sisitemu Yumutima & Cardiology, Pharmacology & Farumasi, na Research & Experimental Medicine. Uruhare runini yagize mu muryango w’amasomo rwatumye amenyekana cyane, nk'uko bigaragazwa n’uko yahisemo inshuro nyinshi nka 'Umushakashatsi wavuzwe cyane mu bijyanye n’ubuvuzi bwa Clinical ' kuva mu 2017 kugeza mu 2024, agaragaza umwanya afite n’uruhare rukomeye mu bushakashatsi bw’ubuvuzi. Rosenstock J yanditse kurutonde rwerekana [4].
