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TirzepatidStructure Imiterere ya
Inkomoko: PubChem |
Urukurikirane: Tyr- {Aib} -Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile- {Aib} -Leu-Asp-Lys-Ile-Ala-Gln- {diacid-C20-gamm a-Glu- (AEEA) 2-Lys} -Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Inzira ya molekulari: C 225H 348N 48O.68 Uburemere bwa molekuline: 4813 g / mol Numero ya CAS: 2023788-19-2 PubChem CID: 163285897 Synonyme: Zepbound; Mounjaro |
Research Ubushakashatsi bwa Tirzepatid
Ni ubuhe bushakashatsi bwakozwe na Tirzepatid?
Tirzepatid nibiyobyabwenge bya polypeptide. Ubushakashatsi niterambere byacyo bituruka ku gusobanukirwa byimazeyo aho ubushobozi bwa GLP-1 bwakira reseptor agonist mu kuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije muri kiriya gihe. Nubwo agoniste ya GLP-1 yerekanye imikorere myiza mugucunga glucose yamaraso no kugabanya ibiro, abahanga basanze imikorere yabo ya reseptor ya GIP idakomeye, ibyo bikaba bigabanya imikorere yibiyobyabwenge kurwego runaka. Itsinda ry’ubushakashatsi n’iterambere rero ryiyemeje guteza imbere imiti mishya ishobora gukora icyarimwe GIPR na GLP-1R icyarimwe kugira ngo igere ku buryo bunoze kandi bunoze bwo kugenzura amaraso ya glucose no gucunga ibiro [1].
Mugihe cyubushakashatsi niterambere rya Tirzepatid, abahanga bakoze ubushakashatsi bwinshi bwibanze nubushakashatsi bwamavuriro. Mubyiciro byubushakashatsi bwibanze, ubushakashatsi bwinyamaswa bwakoreshejwe mugusuzuma neza imiterere ya farumasi ya Tirzepatid. Ibisubizo byemeje ubushobozi bwayo mu kurwanya glucose yamaraso no kugabanya ibiro, bishyiraho urufatiro rwibizamini byakurikiyeho. Nyuma, Tirzepatid yinjiye mu cyiciro cyo kugerageza, harimo icyiciro cya I, II, na III. Icyiciro cya mbere cyasuzumye cyane cyane umutekano, kwihanganira, hamwe n’imiti ya farumasi, kandi ibisubizo byagaragaje umutekano mwiza no kwihanganira. Icyiciro cya II cyongeye gukora ubushakashatsi ku mikorere n’umutekano bya dosiye zitandukanye ku barwayi bafite metabolism yo mu bwoko bwa 2, mbere yo kumenya urugero rwiza. Icyiciro cyingenzi cya III ibizamini byamavuriro, nkurwego rwa SURPASS rwubushakashatsi, bwarimo umubare munini wabarwayi bafite metabolism yo mu bwoko bwa 2. Ibisubizo byagaragaje ko Tirzepatid yarutaga cyane GLP-1 yakira reseptor agoniste, nka Semaglutid, mu kugabanya glucose yamaraso nuburemere, itanga ibimenyetso bifatika byerekana isoko ryamamaza [1].
Tirzepatid ni polypeptide igizwe na acide 39 amine, kandi imiterere yarahinduwe kugirango iteze imbere na farumasi. Igishushanyo cyacyo cyihariye cyububasha gishobora guhuza ingaruka za incretine ebyiri, GIP na GLP-1, muri molekile imwe, igakora imisemburo ya hormone igira uruhare mukurwanya glucose yamaraso hakoreshejwe uburyo bubiri. By'umwihariko, kuruhande rumwe, ikora kuri pancreas kugirango iteze imbere insuline kandi ibuza glucagon kurekura glucose yamaraso; kurundi ruhande, ikora kuri sisitemu yo hagati yububiko, gutinda gusiba gastrica, kongera guhaga, kugabanya ubushake bwo kurya no gufata ibiryo, no kugera kubicunga ibiro. Ubu buryo bubiri butanga Tirzepatid ibyiza byihariye mu kuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije, bigaha abarwayi uburyo bwo kuvura bwuzuye [1].
Nubuhe buryo bwo gukora bwa Tirzepatid?
Tirzepatid igabanya glucose yamaraso ikoresheje uburyo bwinshi bukurikira:
Gukora kwa GLP-1 Kwakira: Tirzepatid ihuza reseptor ya GLP-1 kuri selile beta pancreatic beta, yigana ibikorwa bya GLP-1 bisanzwe. GLP-1 ni imisemburo ikorwa n amara ningirakamaro mukubungabunga glucose homeostasis. Irashobora guteza imbere insuline, gusohora, no kumva glucose, no kugabanya ururenda rwa glucagon kugirango itere guhaga no guhagarika ubushake bwo kurya. Ku barwayi bafite metabolism yo mu bwoko bwa 2, gusohora kwa insuline bidahagije cyangwa kugabanya ubukana bwa selile kuri insuline biganisha ku maraso glucose. Tirzepatid yongera imisemburo ya insuline ikora reseptor ya GLP-1, igateza imbere glucose yamaraso. Muri icyo gihe kandi, ibikorwa bya reseptor ya GLP-1 birashobora kandi kubuza irekurwa rya glucagon, bikagabanya inkomoko ya glucose yamaraso kandi bikagira uruhare mu kurwanya glucose yamaraso [2].
Gukora kwa GIP yakira: Tirzepatid ikora kubakira GIP, kandi kuyikora birashobora kongera insuline no gusohora. Kwakira GIP biboneka cyane mubice nka selile pancreatic beta selile. Nyuma yo gukora, binyuze mumyanya ndangagitsina yerekana inzira, insuline yiyongera, kandi selile yitabira insuline ikiyongera, bikagabanya glucose yamaraso neza [2] . Izi ngaruka zibiri za reseptor agonist zituma Tirzepatid ikora neza kuruta GLP-1 yakira reseptor agoniste mugutezimbere insuline no kubuza glucagon gusohora [2].
Gutinda Gusohora Gastrici no Kongera Guhaza: Tirzepatide irashobora gutinza ubusa gastrica, ikongerera igihe cyo gutura ibiryo mu gifu, igabanya umuvuduko wo kwinjiza intungamubiri, kandi ikarinda kwiyongera gukabije kwa glucose yamaraso nyuma yinyuma. Ingaruka zayo mu gusiba gastrica iragereranywa nki GLP-1 reseptor agonist. Muri icyo gihe, ikora kuri sisitemu yo hagati yo hagati, ikongera guhaga, igabanya ubushake bwo kurya no gufata ibiryo, ibyo bikaba bikwiranye cyane cyane n’ikibazo cy’umubyibuho ukabije akenshi kijyana n’abarwayi bafite metabolism yo mu bwoko bwa 2, bifasha kunoza insuline ndetse n’imiterere rusange ya metabolike [2].
Kunoza ibyiyumvo bya insuline hamwe na Lipid Metabolism: Tirzepatide irashobora kongera urwego rwa adiponectine, adipocytokine ijyanye no kumva insuline, ifasha kunoza insuline, bigatuma selile zifata neza kandi zigakoresha glucose, no kugabanya glucose yamaraso (Anonymous, 2023). Byongeye kandi, irashobora kandi kunoza imiterere ya lipid, ikagira ingaruka zo gukingira ubuzima bwumutima. Byaragaragaye ko ishobora kuzamura umuvuduko w'amaraso, kugabanya cholesterol ya LDL na triglyceride [3].
Inkomoko: PubMed [5]
Ni ubuhe bushakashatsi bujyanye?
Ingaruka zo gucunga ibiro ku barwayi bafite umubyibuho ukabije na Metabolism yo mu bwoko bwa 2
Ubushakashatsi bwinshi bw’amavuriro bwemeje ko Tirzepatid igira ingaruka zikomeye zo kugabanya ibiro. Mu bushakashatsi bwa 'SURMOUNT-2 ', iki cyiciro cya 3, impumyi ebyiri, impumyi, igenzurwa na platbo yakorewe mu bihugu birindwi. Abakuze (bafite imyaka 18 ans) hamwe na BMI ya 27 kg / m² cyangwa hejuru na HbA₁c ya 7 - 10% bariyandikishije kandi bahabwa amahirwe yo kwakira inshuro imwe mucyumweru inshinge ya Tirzepatid (mg 10 cyangwa mg 15) cyangwa umwanya wa byumweru 72. Ibisubizo byagaragaje ko ku cyumweru cya 72, ijanisha ryo kugabanuka ibiro muri Tirzepatid 10 mg na 15 mg byari -12.8% na -14.7%, ugereranije na -3.2% mu itsinda rya placebo. Ikigereranyo cyo kuvura cya Tirzepatid mg 10 na mg 15 ugereranije na placebo ni -9,6 ku ijana na -11,6 ku ijana, byari bifite imibare ikomeye (p <0.0001). Byongeye kandi, abarwayi benshi bahabwa imiti ya Tirzepatid bageze ku gipimo cyo kugabanya ibiro 5% cyangwa byinshi (79 - 83% vs 32%) (Garvey WT, 2023). Muri ubu bushakashatsi, impuzandengo y'ibiro fatizo yari kg 100.7, BMI yari 36.1 kg / m², naho HbA₁c yari 8.02%. Nyuma y'ibyumweru 72 bivurwa, Tirzepatid ntabwo yagabanije cyane ibiro byumubiri gusa ahubwo yanagize ingaruka nziza mugucunga glucose yamaraso [4].
Gutezimbere Neuropathie ya Diyabete
Ubushakashatsi bwerekanye ko GLP1-RAs ishobora kugabanya ibyago byo guta umutwe ku barwayi bafite metabolism yo mu bwoko bwa 2 mu kunoza kwibuka, kwiga, no gutsinda ubumuga bwo kutamenya. Nka GIP-RA / GLP-1RA ebyiri, mumurongo w'akagari ka neuroblastoma (SHSY5Y), ubushakashatsi bwerekanye ko Tirzepatid igira ingaruka ku bimenyetso byo gukura kw'imitsi (CREB na BDNF), apoptose (igipimo cya BAX / Bcl2), gutandukana (pAkt, MAP2, GAP43, na insuline GLUT4, GLUT1, SORBS1). Ibisubizo byibanda ku ruhare rwa Tirzepatid mu gukora inzira ya pAkt / CREB / BDNF no kumanuka werekana kasake hamwe na neuroprotective efficacy, byerekana ko ishobora kurwanya ingaruka ziterwa na hyperglycemia hamwe no kurwanya insuline kurwego rwa neuronal. Kubwibyo, Tirzepatid irashobora guteza imbere neurodegeneration iterwa na hyperglycemia kandi igatsinda insuline irwanya insuline, igatanga ubumenyi bushya bwo kunoza imitekerereze ya metabolism iterwa na metabolism [5].
Iterambere ryubushakashatsi mukuvura ubwoko bwa 2 Metabolism
Nubwoko bushya bwibiyobyabwenge bya hypoglycemic, Tirzepatid ibaye agoniste ya mbere ya GIP / GLP-1R yemewe yo kuvura metabolism muri Amerika. Ibigeragezo byinshi binini byamavuriro byemeje ko glucose igabanuka ningaruka zo kugabanya ibiro, kandi ifite ubushobozi bwo kurinda umutima. Igitekerezo cya peptide ya syntetique yafunguye ibintu byinshi bitazwi kuri Tirzepatid. Ibigeragezo bikomeje (NCT04166773) nibimenyetso byerekana ko ari imiti itanga icyizere mu bijyanye n'indwara y'umwijima idafite inzoga (NAFLD), impyiko na neuroprotection [6] (Ma Z, 2023).
Ingaruka ndende ya Tirzepatid ku buzima bwumutima
Tirzepatid irashobora kugabanya ibyago byindwara zifata umutima nimiyoboro itera kugabanya ibiro. Ubushakashatsi bwasuzumye ingaruka za Tirzepatid ku mubyibuho ukabije n'indwara z'umutima n'imitsi ku bantu bakuze b'Abanyamerika [7] . Ubushakashatsi bwerekanye ko mu Banyamerika bakuze bemerewe kuvurwa na Tirzepatid, nyuma yo kuvurwa hamwe na mg 15 za Tirzepatid, abagera kuri 70,6% na 56.7% by’abakuze batakaje ≥ 15% na ≥ 20% by’ibiro by’umubiri, bivuze ko umubare w’abantu bafite umubyibuho ukabije wagabanutseho 58.8%. Mu badafite indwara z'umutima n'imitsi, bivugwa ko imyaka 10 y’indwara zifata umutima n’umutima zagabanutse ziva kuri 10.1% 'mbere yo kuvurwa ' zigera kuri 7.7% 'nyuma yo kuvurwa ', ibyago byagabanutseho 2,4% naho ibyago bigabanuka 23,6%, bikumira miliyoni 2 z’indwara zifata umutima.
Mu gusoza, Tirzepatid ni ubwoko bushya bwa agonist ya kabiri ya reseptor ya GIP na GLP-1, ifite akamaro kanini mu kuvura metabolism yo mu bwoko bwa 2 n'umubyibuho ukabije. Irashobora guteza imbere neza gusohora kwa insuline, ikabuza gusohora glucagon, kugenzura neza glucose yamaraso, kugabanya ibyago byingaruka, kunoza imikorere ya selile pancreatic beta selile, gutinda gutera imbere kwa metabolism, kandi bigira ingaruka kumutima. Mu kuvura umubyibuho ukabije, irashobora kugabanya neza gufata ibiryo, ubushake buke, kongera guhaga, gufasha abarwayi bafite umubyibuho ukabije guta ibiro, no kugabanya ibyago by’ingaruka ziterwa n'umubyibuho ukabije. Irashobora kandi kunoza insuline irwanya na metabolism ya lipide. Byongeye kandi, irerekana ubushobozi mukuvura indwara zidasanzwe ziterwa na metabolike nka steatohepatite itari inzoga, syndrome de apnea, no kunanirwa k'umutima, kandi irashobora icyarimwe kunoza ibipimo byinshi bya metabolike, itanga gahunda yuzuye yo kuvura. Uburyo bwayo bwo gutera inshuro imwe mucyumweru biroroshye gukoresha kandi birashobora kunoza uburyo bwo kuvura abarwayi. Mugucunga neza glucose yamaraso nuburemere no kugabanya ibyago byingaruka, birashobora guteza imbere cyane abarwayi kumubiri, bikongera ubushobozi bwibikorwa byabo bya buri munsi nubuzima bwiza, bikongerera icyizere cyo kurwanya indwara, kugabanya imitekerereze yabo, no kunoza imibereho yabo.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Dr. William T. Garvey ni intiti n’umushakashatsi uzwi cyane bifitanye isano n’ibigo byinshi bizwi, birimo kaminuza ya Alabama i Birmingham, kaminuza ya Aston, n’ikigo cy’ubuvuzi cya Birmingham. Amashuri ye n'uburambe bw'umwuga bikubiyemo amasomo atandukanye mu buvuzi na siyansi. Dr. Garvey yagize uruhare runini mu bijyanye na endocrinology na metabolism, imirire n’imirire, ibinyabuzima na biyolojiya y’ibinyabuzima, ndetse n’ubuvuzi rusange ndetse n’imbere, yibanda cyane cyane kuri sisitemu yumutima nimiyoboro yumutima. Ibikorwa bye byamenyekanye cyane kandi byubahwa, cyane cyane byiswe Umushakashatsi wavuzwe cyane mu cyiciro cya Cross-Field mu myaka ya 2023 na 2024, byerekana ingaruka n’ingaruka zikomeye z’ubushakashatsi bwe ku muryango mugari wa siyansi.
Ubushakashatsi bwa Dr. Garvey n'ubuhanga bugera no mu bice bitandukanye by'indwara ziterwa na metabolike. Yagize uruhare runini mu kwiga metabolism mellitus, umubyibuho ukabije, hamwe n’ibibazo bifitanye isano nayo, agamije kuvumbura ingamba zo kuvura udushya no kunoza umusaruro w’abarwayi. Ibikorwa bye bikubiyemo ubushakashatsi bwibanze bwa siyansi, ibizamini by’amavuriro, n’ubushakashatsi bw’ubuhinduzi, bikuraho itandukaniro riri hagati y’ibyavuye muri laboratoire hamwe n’ubuvuzi busanzwe ku isi. Binyuze mu bushakashatsi bwe bunini, Dr. Garvey yagize uruhare mu gusobanukirwa byimbitse n’uburyo bw’imiterere y’imihindagurikire y’imihindagurikire y’ikirere kandi yafashije mu gushyiraho umurongo ngenderwaho w’amavuriro na protocole y’ubuvuzi mu bijyanye na endocrinology na metabolism. Dr. William T. Garvey yanditse ku rutonde rw'ibitekerezo [4 ].
