Cagrilintide ni peptide ya syntetique yigana imikorere ya amylin, imisemburo isohoka na pancreas igenga urugero rwa glucose yamaraso no kurya.Igizwe na aside amine 38 kandi irimo umurunga wa disulfide.Cagrilintide ihuza byombi byakira amylin (AMYR) hamwe na reseptor ya calcitonine (CTR), ari byo byakira poroteyine G bigaragarira mu ngingo zitandukanye, nk'ubwonko, pancreas, n'amagufwa.Mugukoresha ibyo byakira, cagrilintide irashobora kugabanya gufata ibiryo, kugabanya glucose yamaraso, no kongera ingufu zikoreshwa.Cagrilintide yakozweho ubushakashatsi nk'uburyo bushobora kuvura umubyibuho ukabije, indwara ya metabolike irangwa n'amavuta menshi yo mu mubiri ndetse no kongera ibyago bya diyabete, indwara z'umutima n'imitsi.Cagrilintide yerekanye ibisubizo bitanga umusaruro mubushakashatsi bwinyamaswa no kugerageza kwa muganga, byerekana kugabanuka gukabije no kurwanya indwara ya glycemic kubarwayi bafite umubyibuho ukabije urwaye diyabete yo mu bwoko bwa 2 cyangwa badafite.
Igicapo 1. Icyitegererezo cya homologiya ya cagrilintide (23) ihujwe na AMY3R.. reseptor..AMY3R ikorwa na CTR (imvi) ihujwe na RAMP3 (reseptor-ibikorwa bihindura poroteyine 3; orange).Icyitegererezo cyubatswe cyakozwe hifashishijwe inyandikorugero zikurikira: imiterere igoye ya CGRP (reseptor ya calcitonine imeze nka reseptor; pdb code 6E3Y) hamwe na apo kristaliste ya 23 ya rugongo (kode ya pdb 7BG0).. JL, Dahl K, Schäffer L, Sensfuss U, Poulsen C, Schlein M, Hansen AMK, Jeppesen CB, Dornonville de la Cour C, Clausen TR, Johansson E, Fulle S, Skyggebjerg RB, Raun K. Iterambere rya Cagrilintide, Long -Gukora Amylin Analogue. J Med Chem. 2021 Kanama 12; 64 (15): 11183-11194.)
Bimwe mubikorwa byibinyabuzima bya cagrilintide ni:
Cagrilintide irashobora guhindura ibikorwa bya neuron muri hypothalamus, agace k'ubwonko kayobora ubushake bwo kurya no gukomera (Lutz et al., 2015, Front Endocrinol (Lausanne)).Cagrilintide irashobora kubuza kurasa kwa neurone ya orexigenic itera inzara, kandi igakora neuron ya anorexigenic, ihagarika inzara.Kurugero, cagrilintide irashobora kugabanya imvugo ya neuropeptide Y (NPY) na peptide ifitanye isano na agouti (AgRP), peptide ebyiri zikomeye za orexigenic, kandi bikongera imvugo ya proopiomelanocortin (POMC) na kokayine- na amphetamine igengwa na transcript (CART), bibiri peptide ya anorexigenic, muri arcuate nucleus ya hypothalamus (Roth et al., 2018, Physiol Behav).Cagrilintide irashobora kandi kongera imbaraga zo guhaza leptine, imisemburo yerekana imbaraga z'umubiri.Leptin isohorwa na tipusi ya adipose kandi ihuza reseptor ya leptine kuri neuron ya hypothalamic, ikabuza neurone ya orexigenic no gukora neuron ya anorexigenic.Cagrilintide irashobora kongera ibyiyumvo bya reseptor ya leptin hamwe na potentiate leptin iterwa no gukora ibimenyetso bya transducer hamwe nuwatangije transcription 3 (STAT3), ibintu byandika byerekana ingaruka za leptine kumagambo ya gene (Lutz et al., 2015, Front Endocrinol (Lausanne)) .Izi ngaruka zirashobora kugabanya gufata ibiryo no kongera ingufu zikoreshwa, biganisha ku kugabanuka.
Igicapo 2. Ifunguro ryibiryo byimbeba nyuma yubuyobozi bwa Cagrilintide 23. (byahinduwe na Kruse T, Hansen JL, Dahl K, Schäffer L, Sensfuss U, Poulsen C, Schlein M, Hansen AMK, Jeppesen CB, Dornonville de la Cour C, Clausen TR, Johansson E, Fulle S, Skyggebjerg RB, Raun K. Iterambere rya Cagrilintide, Analogue ikora Amylin. J Med Chem. 2021 Kanama 12; 64 (15): 11183-11194.)
Cagrilintide irashobora kugenga ururenda rwa insuline na glucagon, imisemburo ibiri igenzura urugero rwa glucose.Cagrilintide irashobora kubuza glucagon isohoka muri selile ya alpha muri pancreas, irinda glucose gukora cyane umwijima.Glucagon ni imisemburo itera isenyuka rya glycogene hamwe na synthesis ya glucose mu mwijima, bikazamura urugero rwa glucose mu maraso.Cagrilintide irashobora guhagarika ururenda rwa glucagon muguhuza reseptor ya amylin hamwe na reseptor ya calcitonine kuri selile ya alpha, ihujwe no kubuza poroteyine G kugabanya urugero rwa adenosine monophosphate (cAMP) hamwe na calcium yinjira.Cagrilintide irashobora kandi kongera imbaraga za insuline ziva mu ngirabuzimafatizo za beta ziri mu gifu, zongerera glucose gufata imitsi hamwe na tipusi ya adipose.Insuline ni imisemburo iteza imbere kubika glucose nka glycogene mu mwijima no mu mitsi, no guhindura glucose na aside irike mu ngingo za adipose, bikagabanya urugero rwa glucose.Cagrilintide irashobora kongera imisemburo ya insuline ihuza reseptor ya amylin hamwe na reseptor ya calcitonine kuri selile beta, ihujwe na poroteyine G itera imbaraga zongera urugero rwa cAMP hamwe na calcium yinjira.Izi ngaruka zirashobora kugabanya urugero rwa glucose yamaraso no kunoza insuline, ishobora gukumira cyangwa kuvura diyabete yo mu bwoko bwa 2 (Kruse et al., 2021, J Med Chem; Dehestani et al., 2021, J Obes Metab Syndr.).
Cagrilintide irashobora kandi kugira ingaruka kumikorere ya osteoblasts na osteoclasts, ubwoko bubiri bw'utugingo ngengabuzima tugira uruhare mu kurema amagufwa no kwisubiraho.Osteoblasts ishinzwe kubyara matrix nshya, mugihe osteoclasts ishinzwe kumena matrike ishaje.Uburinganire hagati ya osteoblasts na osteoclasts bugena amagufwa n'imbaraga.Cagrilintide irashobora gutuma osteoblast itandukana nibikorwa, byongera amagufwa.Cagrilintide irashobora guhuza reseptor ya amylin hamwe na reseptor ya calcitonine kuri osteoblasts, ikora inzira yerekana ibimenyetso byerekana inzira ituma ikwirakwizwa rya osteoblast, kubaho, hamwe na synthesis ya matrix (Cornish et al., 1996, Biochem Biophys Res Commun.).Cagrilintide irashobora kandi kongera imvugo ya osteocalcine, ikimenyetso cyo gukura kwa osteoblast n'imikorere (Cornish et al., 1996, Biochem Biophys Res Commun.).Cagrilintide irashobora kandi kubuza itandukaniro rya osteoclast hamwe nibikorwa, bigabanya amagufwa.Cagrilintide irashobora guhuza reseptor ya amylin hamwe na reseptor ya calcitonine kubibanjirije osteoclast, bibuza guhuza kwabo muri osteoclasts ikuze (Cornish et al., 2015).Cagrilintide irashobora kandi kugabanya imvugo ya fosifata ya aside irwanya tartrate (TRAP), ikimenyetso cyibikorwa bya osteoclast hamwe no gufata amagufwa (Cornish et al., 2015, Bonekey Rep.).Izi ngaruka zirashobora kunoza imyunyu ngugu yamagufa no gukumira cyangwa kuvura osteoporose, indwara irangwa nubwinshi bwamagufwa kandi byongera ibyago byo kuvunika (Kruse et al., 2021; Dehestani et al., 2021, J Obes Metab Syndr.)
