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▎ Nkọwa nke Cagrilintide
Cagrilintide bụ amylin dual na calcitonin agonist receptor (DACRA) nke emebere dabere na nhazi nke amylin. Ọ na-arụ ọrụ site na ịgbalite ma onye na-anabata amylin na onye na-anabata calcitonin, si otú ahụ na-egosipụta ikike iji gbanwee usoro metabolic, gụnyere ịdị arọ ahụ na ọkwa glucose ọbara. Amylin, hormone nke mkpụrụ ndụ pancreatic zoro ezo, na-arụ ọrụ dị mkpa n'ịkwalite satiety, nke na-emesị na-ebute mbelata nke oriri. Ọzọkwa, amylin na-enye aka na nhazi nke metabolism glucose ọbara site n'ọtụtụ usoro, dị ka igbochi mwepụta nke glucagon postprandial na ibelata mkpofu gastric. Iji dozie mmachi a, ewepụtara Cagrilintide dị ka analọgụ na-eme ogologo oge, na-egosipụta ọkara ndụ ihe dịka ụbọchị 7 ruo 8. Nke a gbatịkwuru ọkara ndụ na-akwalite ịdị mma nke nchịkwa yana nnabata ndị ọrịa, na-enye nhọrọ ọgwụgwọ bara uru karị.
▎ Ọdịdị Cagrilintide
Isi mmalite: PubChem |
Usoro: Pyr-KCNTACATQRLAEFLRHSSNNFGPILPPTNVGSNTP CAS: 1415456-99-3 Formula: C 174H 269N 45O 52S2 MW 4409 g/mol |
▎ Nnyocha nke Cagrilintide
Gịnị bụ isi mmalite nke Cagrilintide?
Cagrilintide - analog nke amylin:
Amylin bụ homonụ nke emepụtara site na sel beta nke agwaetiti pancreatic. N'okpuru ọnọdụ physiological, ọ na-arụkọ ọrụ na insulin ma nwee ọtụtụ ọrụ physiological dị mkpa.
Nke mbụ, amylin na-arụ ọrụ dị mkpa n'ịkwalite satiety na ibelata oriri. Usoro ya na-emekarị gụnyere ịgbalite ndị nnabata na Mpaghara Postrema na ala nke ventricle nke anọ. A na-ebufe akara akwara na ụbụrụ ihu site na Nucleus of the Solitary Tract. N'otu oge ahụ, a pụkwara ibuga ha na Mpaghara Hypothalamic Lateral na ìgwè nuklia hypothalamic ndị ọzọ site na Lateral Parabrachial Nucleus. Amylin nwere ikike ịkpali satiety center nke organism ma gbochie iri nri na anụmanụ [1].
Amylin nwere ike ịhazi glucose homeostasis, nke a na-enweta site na igbochi nzuzo nke ma insulin na glucagon [2] . Ọrụ a na-enye aka nke ukwuu n'ịkwado nkwụsi ike nke ọkwa glucose ọbara ma na-ejide nnukwu mkpa maka ọgwụgwọ ọrịa dịka ọrịa shuga.
Ọzọkwa, amylin na-arụ ọrụ ya site na-emetụta ntọhapụ nke neurotransmitters. Dịka ọmụmaatụ, ọ na-egbochi ntọhapụ nke dopamine na hypothalamus nke oke, ebe ọ na-enwe mmetụta dị ntakịrị na norepinephrine na serotonin [3] . N'ihe banyere glucose homeostasis, amylin na-ejigide nkwụsi ike nke glucose ọbara site na ibelata nzuzo nke insulin na glucagon. Usoro ya na-agụnye ime ihe ozugbo na sel sel sel pancreatic yana na-achịkwa secretion glucagon na-apụtaghị ìhè site na ntụgharị mgbaàmà akwara na hypothalamus. N'ime ndị ọrịa nwere ọrịa shuga, mbibi nke mkpụrụ ndụ β abụghị naanị na-eduga na ụkọ insulin kamakwa ọ na-ebute mbelata nzuzo nke ma C-peptide na amylin. O doro anya na Amylin na-etinye aka na nhazi nke glucose homeostasis site na igbochi nsị gastric na mmepụta glucose hepatic hepatic postprandial, n'ikpeazụ na-ebelata ngbanwe nke glucose ọbara postprandial [4] . Tụkwasị na nke a, amylin nwere ike igbu oge ịpụsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịsịta, na-egbochi peristalsis nke eriri afọ site na usoro nhụjuanya nke etiti, ma mee ka oge obibi nke nri dị na tract gastrointestinal, si otú ahụ gbochie mmụba ngwa ngwa nke glucose ọbara.
Ka o sina dị, amylin nwere obere ọkara ndụ, nke na-egbochi ngwa ụlọ ọgwụ ya. Nnyocha na-egosi na analog amylin dị adị, pramlintide, dị ka ọgwụ enyemaka maka ọgwụgwọ ọrịa shuga, chọrọ nchịkwa ugboro atọ n'ụbọchị. Ọ bụghị nanị na nke a na-akpata nsogbu nye ndị ọrịa kamakwa ọ na-ebelata nnabata ha [5] . Iji dozie okwu nke obere ọkara ndụ nke amylin eke, emepụtara Cagrilintide dị ka analog na-eme ogologo oge. Mmepe nke Cagrilintide dabere na nghọta miri emi nke ọrụ physiological nke amylin eke. Ọ na-achọ ime ka usoro nke amylin na-eme ihe mgbe ọ na-eme ka nkwụsi ike na ihe na-eme ogologo oge nke ọgwụ ahụ iji mezuo ihe achọrọ maka ọgwụgwọ ụlọ ọgwụ.
Njirimara nwere ike na ọgwụ nke Cagrilintide
Cagrilintide bụ analog nke amylin na-eme ogologo oge nwere ikike dị egwu, na-egosipụta mmetụta dị ịrịba ama na ọgwụgwọ oke ibu na ọrịa shuga. Ọ nwere egbugbere ọnụ ma nwee njirimara ọ na-eme ogologo oge [5] . Amylin bụ homonụ nke sel β pancreatic na-ewepụta yana insulin, nke na-ebute satiety site na ime ihe na mpaghara homeostatic na hedonic nke ụbụrụ. Dị ka ihe analog nke amylin, Cagrilintide nwere ike iṅomi mmetụta a, na-ebute satiety ma si otú a na-enyere aka ịchịkwa ibu. Ọzọkwa, Cagrilintide bụ amylin dual na calcitonin agonist receptor, nke sitere na ọkpụkpụ azụ amylin, na-enye ya usoro pụrụ iche nke ime ihe na usoro metabolic.
Ọganihu nke ọmụmụ ụlọ ọgwụ na Cagrilintide
N'ime ule ụlọ ọgwụ, Cagrilintide ewepụtala nsonaazụ na-ekwe nkwa na-ebute mbelata ibu. Dịka ọmụmaatụ, n'ime multicenter, randomized, kpuru ìsì abụọ, ebe a na-achịkwa ebebo, yana na-arụsi ọrụ ike na-achịkwa usoro 2 dose-nyocha nnwale, ndị sonyere na Cagrilintide gosipụtara mbelata ịdị arọ nke ukwuu ma e jiri ya tụnyere ndị na-anata placebo. Pasent nke mbelata ịdị arọ sitere na ntọala maka usoro ọgwụgwọ Cagrilintide niile (0.3 - 4.5 mg) dị elu (6.0% - 10.8%) karịa nke otu placebo (3.0%). Mbelata ịdị arọ nke otu a na-eji 4.5 mg nke Cagrilintide dịkwa ukwuu karịa nke a na-emeso ya na 3.0 mg nke liraglutide (10.8% vs. 9.0%). Nsonaazụ ndị a na-egosi na Cagrilintide nwere ike ịbụ nhọrọ dị irè maka njikwa ibu [6].
Cagrilintide na GLP-1 agonist agonist semaglutide nwere usoro omume dị iche ma jikọtara ya. Semaglutid na-arụ ọrụ ya site na ime ihe na ndị na-anabata GLP-1 na hypothalamus, nke na-eduga n'ịbelata agụụ, mmụba na nzuzo insulin, na igbu oge na mkpofu gastric. N'aka nke ọzọ, Cagrilintide na-ebelata agụụ site na ịgbalite ndị na-anabata amylin. Nchịkọta nchịkwa nke ndị ọrụ abụọ a na-ebute mmetụta dị elu na agụụ site n'ọtụtụ usoro, na-eme ka arụmọrụ dị arọ dịkwuo elu [7] . N'inye ọdịdị dị mgbagwoju anya nke oke oke ibu, ọgwụgwọ nchikota na-elekwasị anya n'ọtụtụ njedebe pathophysiological na-anọchite anya atụmatụ ezi uche na nke dị irè.
Ọzọkwa, Cagrilintide egosipụtala ikike njikwa glucose ọbara na-ekwe nkwa na ndị ọrịa nwere ụdị ọrịa shuga 2. Nnyocha ụlọ ọgwụ egosila na Cagrilintide na-egosipụta nkwụsi ike na ịdị mma na njikwa oke oke yana ụdị ọrịa shuga 2. Dịka ọmụmaatụ, na nnwale ụlọ ọgwụ metụtara ndị ọrịa nwere ụdị ọrịa shuga 2, njikọta Cagrilintide na GLP-1 agonist semaglutide gosipụtara njikwa glucose ọbara dị ịrịba ama na mmetụta mbelata ibu. Nke a na-egosi na Cagrilintide na-edobe nkwụsi ike dị elu na omume ụlọ ọgwụ ma nwee ike ịmepụta mmetụta ọgwụgwọ na-adịgide adịgide. Na nnwale ụlọ ọgwụ ọzọ, Cagrilintide, ma ọ bụ naanị ya ma ọ bụ jikọtara ya na semaglutide, gosipụtara nnabata na nchekwa dị mma [8] . Nke a na-akwado nkwụsi ike nke Cagrilintide, dịka na ngwa ụlọ ọgwụ, nkwụsi ike nke ọgwụ na-ejikọta ya na nnabata ya na nchekwa ya.
N'ikpeazụ, na ule ụlọ ọgwụ, a kwadoro ọgwụgwọ na cagrilintide nke ọma. N'ime usoro nchọpụta ọnụọgụ nke 2, ọnụ ọgụgụ nke nkwụsị ọgwụgwọ na-adịgide adịgide bụ nke a na-atụnyere n'ofe ụdị ọgwụgwọ dị iche iche, nke na-ebutekarị na ihe ọjọọ. Ka o sina dị, ihe ọjọọ kachasị emetụta bụ ọrịa eriri afọ na mmeghachi omume ebe ịgba ọgwụ mgbochi, nke ọtụtụ na-adị nwayọọ ma na-agafeghị oke. N'ime usoro 1b nke a na-achịkwaghị achịkwa, ọgwụgwọ a na-eme n'otu oge na cagrilintide na 2.4 mg nke semaglutide gosikwara ezigbo nnabata yana profaịlụ nchekwa anabatara [9]. Ọnwụnwa buru ibu na ogologo oge ka akwadoro n'ọdịnihu iji nyochaa nke ọma ịdị irè na nchekwa nke ọgwụgwọ ngwakọta a.

Ụdị ihe owuwu nke Cagrinlintide
Isi mmalite: PubMed [5]
Ihe bara uru nke iji Cagrilintide
Mpụta nke Cagrilintide ewetala olileanya ọhụrụ na ọgwụgwọ oke ibu na ụdị ọrịa shuga 2. N'agbanyeghị oke nsogbu oke ibu zuru ụwa ọnụ na-abawanye, nhọrọ ndị akwadoro ugbu a maka ọgwụgwọ ọgwụ ka nwere oke. Dị ka akwụkwọ akụkọ amylin analogue na-eme ogologo oge, Cagrilintide na-enye nhọrọ ọgwụgwọ ọhụrụ maka ndị ọrịa buru ibu, ọkachasị ndị na-enweghị nzaghachi na-adịghị mma na ntinye ndụ na-adabaghị maka ịwa ahụ bariatric. Ọ na-enweta njikwa ibu site na usoro pụrụ iche nke ime ihe, na-enye echiche ọhụrụ na ụzọ maka ọgwụgwọ oke ibu, ma ọ nwere ike igosipụta ịdị mma na nchekwa dị mma ma e jiri ya tụnyere ọgwụ mgbochi oke ibu [7] . Ọzọkwa, ihe ịga nke ọma nke nchikota nke Cagrilintide na semaglutide (CagriSema) na-egosi na ọgwụgwọ nchikota na-elekwasị anya n'ọtụtụ ebumnuche pathophysiological bụ atụmatụ dị irè maka ịkwalite nzaghachi ọgwụgwọ na oke ibu [8] . Usoro ọgwụgwọ ọtụtụ ebumnuche a abụghị naanị na-enye usoro ọhụrụ maka njikwa oke oke mana ọ na-ewetakwa nkwalite metabolic dị ukwuu na ndị ọrịa nwere ụdị ọrịa shuga 2.
Na mmechi, dị ka akwụkwọ akụkọ amylin analogue na-eme ogologo oge, Cagrilintide nwere ikike dị ịrịba ama maka mbelata ibu na njikwa glucose ọbara. Ọ na-eme ka ụzọ mgbama satiety rụọ ọrụ site n'iṅomi omume amylin ma na-achịkwa metabolism dị ka onye na-anabata ihe abụọ. Nnwale ụlọ ọgwụ egosila na Cagrilintide, nke ejiri ya naanị ya ma ọ bụ yana yana semaglutide, nwere ike belata ibu ahụ nke ukwuu ma na-anabata ya nke ọma. Na mgbakwunye, o gosipụtala ikike njikwa glucose ọbara dị mma na ndị ọrịa nwere ụdị ọrịa shuga 2, na-enye nhọrọ ọhụrụ maka ọgwụgwọ oke ibu na ọrịa shuga yana mejupụta oghere na usoro ọgwụgwọ dị ugbu a, ọkachasị maka ndị ọrịa na-anabata nzaghachi na-adịghị mma maka enyemaka ndụ na ndị na-adabaghị maka ịwa ahụ. Usoro ọgwụgwọ ọtụtụ ebumnuche ya na-enye nghọta ọhụrụ maka njikwa ọrịa metabolic.
Banyere Onye dere ya
Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.
Onye ode akwụkwọ akụkọ sayensị
Dr. DCW Lau bụ prọfesọ na Cumming School of Medicine, Mahadum Calgary, Canada. Ebumnuche nyocha ya na-ekpuchi endocrinology na metabolism, ọgwụ izugbe na nke ime, sistemu obi na akwara obi, ahụike ọha, ahụike gburugburu ebe obibi na ọrụ, yana oncology. Ọ na-ejikwa ọrụ na Alberta Health Services (AHS) na Obesity Canada ma na-arụ ọrụ na Julia McFarlane Diabetes Research Center. Dr. Lau nwere ahụmahụ dị ukwuu n'ihe gbasara ọrịa shuga na nchọpụta oke ibu, na-ebipụta ọrụ ya na akwụkwọ akụkọ agụmakwụkwọ dị ka Canadian Journal of Diabetes. Dọkịta DCW ka edepụtara na ntụnye aka nke ntụaka [6].
▎ Okwu ndị dị mkpa
[1] Hansen KE, Murali S, Chaves IZ, Suen G, Ney DM. Mmetụta Glycomacropeptide Amylin-Mediated Satiety, Postprandial Markers of Glucose Homeostasis, na Fecal Microbiome na Obese Postmenopausal Women. J NUTR 2023; 153 (7): 1915-29 . DOI:10.1016/j.tjnut.2023.03.014.
[2] Ling W, Huang Y, Qiao Y, Zhang X, Zhao H. Human Amylin: Site na Pathology ruo Physiology na Pharmacology. CURR PROTEIN PEPT SC 2019; 20 (9): 944-57 . DOI:10.2174/ 13892037206 66 19032811183 3.
[3] Brunetti L, Recinella L, Orlando G, Michelotto B, Di Nisio C, Vacca M. Mmetụta ghrelin na amylin na dopamine, norepinephrine na serotonin ntọhapụ na hypothalamus. EUR J PHARMACOL 2002; 454 (2-3): 189-92. DOI:10.1016/S0014-2999(02)02552-9.
[4] Gedulin BR, Jodka CM, Herrmann K, Young AA. Ọrụ nke amylin endogenous na nzuzo nke glucagon na mkpofu gastric n'ime oke egosipụtara na onye na-emegide ahọpụtara, AC187. Peptides na-achịkwa 2006; 137 (3): 121-7. DOI:10.1016/j.regpep.2006.06.004.
[5] Kruse T, Hansen JL, Dahl K, et al. Mmepe nke Cagrilintide, Amylin Analogue na-eme ogologo oge. J MED CHEM 2021; 64 (15): 11183-94 . DOI:10.1021/acs.jmedchem.1c00565.
[6] Lau DCW, Erichsen L, Francisco AM, et al. Otu ugboro kwa izu cagrilintide maka njikwa ibu na ndị nwere oke ibu na oke ibu: multicentre, randomized, double-kpuru, ebe a na-achịkwa ebe a na-achịkwa na njikwa na-arụ ọrụ, na-achọpụta dose 2 nnwale. LANCET 2021; 398 (10317): 2160-72 . DOI:10.1016/S0140-6736(21)01751-7.
[7] D'Ascanio AM, Mullally JA, Frishman WH. Cagrilintide: Amylin Analog na-eme ogologo oge maka ọgwụgwọ oke ibu. CARDIOL REV 2024; 32 (1): 83-90. DOI:10.1097/CRD.000000000000513.
[8] Frias JP, Deenadayalan S, Erichsen L, et al. Ịdị irè na nchekwa nke ọnụ ọgụgụ cagrilintide 2.4 mg otu ugboro kwa izu yana semaglutide 2.4 mg otu ugboro kwa izu na ụdị ọrịa shuga 2: multicentre, randomized, kpuru ìsì abụọ, na-arụ ọrụ na-arụ ọrụ, usoro 2. LANCET 2023; 402 (10403): 720-30. DOI:10.1016/S0140-6736(23)01163-7.
[9] Enebo LB, Berthelsen KK, Kankam M, et al. Safety, nnabata, pharmacokinetics, na pharmacodynamics nke concomitant nchịkwa nke ọtụtụ doses nke cagrilintide na semaglutide 2.4 mg maka arọ njikwa: a randomized, akara, usoro 1b ikpe. LANCET 2021; 397 (10286): 1736-48 . DOI:10.1016/S0140-6736(21)00845-X.
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.