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▎ Nkọwa nke Cagrilintide
Cagrilintide bụ amylin dual na calcitonin agonist receptor (DACRA) mepụtara dabere na nhazi nke amylin. Ọ na-arụ ọrụ ya site na ịgbalite amylin receptor na calcitonin receptor, si otú a na-egosipụta ikike ịhazi usoro metabolic dị ka ibu ahụ na ọkwa glucose ọbara.
Nnyocha na mmepe nke Cagrilintide sitere na njirimara physiological nke amylin eke. Amylin eke bụ homonụ nke mkpụrụ ndụ pancreatic zoro ezo ma na-arụ ọrụ dị mkpa n'ịkwalite satiety na ibelata iri nri. N'otu oge ahụ, ọ na-ekerekwa òkè na nhazi nke metabolism glucose ọbara site na usoro dị iche iche, dị ka igbochi mwepụta nke glucagon postprandial na igbu oge mkpofu gastric.
Dị ka analog na-eme ogologo oge, Cagrilintide nwere ọkara ndụ ihe dịka ụbọchị 7 ruo 8. Nke a ogologo ndụ ọkara ndụ na-eme ka mma nchịkwa na nnabata ndị ọrịa dịkwuo mma, na-eme ka ọ bụrụ 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
Kedu ihe ndabere nyocha nke Cagrilintide?
Cagrilintide bụ amylin dual na calcitonin agonist receptor (DACRA) mepụtara dabere na nhazi nke amylin. A na-ezobe Amylin site na mkpụrụ ndụ beta nke pancreatic ma na-arụkọ ọrụ na insulin iji rụọ ọrụ dị iche iche nke anụ ahụ. Ọ nwere ike ịkpata mmetụta nke satiety ma belata oriri nri, tumadi site na ịgbalite ndị na-anabata ya na mpaghara postrema na ala nke ventricle nke anọ. A na-ebufe akara akwara na ụbụrụ ụbụrụ site na nucleus nke traktị naanị ya, a pụkwara ibunye ya na mpaghara hypothalamic mpụta na ndị ọzọ dị iche iche nuklia site na mpụta parabrachial nucleus, si otú ahụ na-akpali satiety center na igbochi oriri [1] . Amylin nwekwara ike ịhazi glucose homeostasis site na igbochi nzuzo nke insulin na glucagon iji nọgide na-enwe ọkwa glucose ọbara kwụsiri ike [2] . Usoro ya gụnyere mmetụta ozugbo na sel sel sel pancreatic na usoro na-apụtaghị ìhè nke glucagon secretion site na akara akwara na hypothalamus. N'ime ndị ọrịa nwere ọrịa shuga, mbibi nke mkpụrụ ndụ β na-eduga na mbelata nke nzuzo amylin. Amylin na-ekere òkè na nhazi nke glucose homeostasis site na igbochi mkpofu gastric na mmepụta glucose imeju postprandial, na-ebelata mmụgharị nke glucose ọbara postprandial. Ọ nwekwara ike na-egbu oge ịgbasa afọ, na-egbochi eriri afọ peristalsis, gbatịa oge obibi nri, ma gbochie mmụba dị ukwuu na glucose ọbara. Agbanyeghị, ọkara ndụ dị mkpụmkpụ nke amylin eke na-egbochi ngwa ụlọ ọgwụ ya. Ọ bụ ezie na pramlintide dị dị ka ọgwụ adjuvant, ọ na-achọ injections atọ kwa ụbọchị, nke na-adịghị mma ma na-ebute nrubeisi na-adịghị mma [3] . Iji dozie nsogbu a, e mepụtara Cagrilintide. Nnyocha ya na mmepe ya dabere na nghọta miri emi nke ọrụ physiological nke amylin eke, na-achọ iṅomi usoro ya na-eme ka ọ dịkwuo mma na nkwụsi ike na ogologo oge nke ọgwụ iji gboo mkpa ụlọ ọgwụ.
Kedu ihe bụ Cagrilintide?
Cagrilintide bụ analog amylin na-eme ogologo oge nwere ikike dị ukwuu, ebe egosilarị ịdị irè mbụ na ọgwụgwọ oke ibu na ọrịa shuga. Ọ bụ lipidated ma nwee àgwà kwụsiri ike na ogologo oge [3] . A na-ewepụta Amylin na insulin site na mkpụrụ ndụ beta pancreatic ma na-ebute mmetụta nke afọ ojuju site na ime ihe na mpaghara homeostatic na obi ụtọ nke ụbụrụ. Dị ka analog, Cagrilintide nwere ike iṅomi mmetụta a, na-akpali satiety iji nyere aka ịchịkwa ibu ahụ. N'otu oge ahụ, dị ka amylin dual na calcitonin agonist receptor (DACRA), ọ sitere na ọkpụkpụ azụ amylin ma nwee usoro pụrụ iche na nhazi usoro metabolic.

Ụdị ihe owuwu nke Cagrinlintide
Isi mmalite: PubMed [3]
Kedu ihe bụ ngwa ndị metụtara Cagrilintide?
N'ime ule ụlọ ọgwụ, Cagrilintide enwetala nsonaazụ dị mma n'ịkwalite ibu ibu. Dị ka ọmụmaatụ, na multicenter, randomized, okpukpu abụọ-kpuru, placebo-achịkwa, na onye na-arụ ọrụ comparator Phase 2 dose-nyocha nnwale, ma e jiri ya tụnyere placebo otu, nkezi pasent nke arọ ọnwụ site na ndabere na nke ọ bụla dose otu Cagrilintide (0.3 - 4.5 mg) (6.0% - 10.8%) dị elu karịa nke ahụ na placebo otu (3.0%). Mbelata dị arọ na 4.5 mg otu dịkwa ukwuu karịa na liraglutide 3.0 mg otu (10.8% vs. 9.0%), na-egosi na ọ nwere ike ịbụ nhọrọ dị irè maka njikwa ibu [4] . Cagrilintide nwere usoro ọrụ dị iche mana metụtara ya ma e jiri ya tụnyere GLP-1 agonist agonist semaglutide. Semaglutid na-ebelata agụụ, na-abawanye mmepụta insulin, ma na-egbu oge ịpụsị afọ site na ime ihe na GLP-1 ndị na-anabata ya na hypothalamus, ebe Cagrilintide na-ebelata agụụ site na ịgbalite amylin receptor. Ejikọtara ọnụ nke abụọ ahụ nwere ike ịmepụta mmetụta dị elu, na-eme ka mmetụta mbelata dị arọ [5] . N'iburu mgbagwoju anya nke oke ibu, ọgwụgwọ a jikọtara ọnụ bụ atụmatụ ezi uche dị na ya ma dị irè.
N'ime ndị ọrịa nwere ụdị ọrịa shuga 2, Cagrilintide egosipụtakwala ike njikwa glucose ọbara dị mma. Nnyocha ụlọ ọgwụ egosila na ọ nwere ezigbo nkwụsi ike na ịdị irè na ọgwụgwọ oke ibu na ụdị ọrịa shuga 2. Dịka ọmụmaatụ, na nnwale ụlọ ọgwụ nke ndị ọrịa nwere ụdị ọrịa shuga 2, ijikọ Cagrilintide na GLP-1 agonist agonist semaglutide gosipụtara ezigbo njikwa glucose ọbara na mmetụta mbelata ibu [6] . Ọnwụnwa ọzọ gosikwara ịdị mma ya na nchekwa ya mgbe ejiri ya naanị ya ma ọ bụ yana semaglutide [6] , n'ihi na nkwụsi ike nke ọgwụ ahụ nwere njikọ chiri anya na nnabata ya na nchekwa ya.
Na mgbakwunye, Cagrilintide anabatala nke ọma na nnwale ụlọ ọgwụ. N'ime usoro nchọpụta dose nke 2, ọnụ ọgụgụ nkwụsị na-adịgide adịgide na otu ọgwụgwọ ọ bụla yiri nke ahụ, nke ka ukwuu n'ihi ihe ọjọọ. Otú ọ dị, ihe ọjọọ na-emekarị bụ nsogbu eriri afọ na mmeghachi omume n'ebe injection, na ọtụtụ n'ime ha dị nwayọọ ma na-agafeghị oke. N'ime usoro 1b nke a na-achịkwaghị achịkwa, ọgwụgwọ jikọtara ọnụ nke Cagrilintide na 2.4 mg semaglutide gosikwara ezigbo nnabata na nchekwa [7] . Ọnwụnwa buru ibu na ogologo oge dị mkpa n'ọdịnihu iji nyochaa nke ọma ịdị irè na nchekwa nke ọgwụgwọ a jikọtara ọnụ.
Cagrilintide na-eweta olileanya ọhụrụ maka ọgwụgwọ oke ibu na ụdị ọrịa shuga 2. Ọ na-enye nhọrọ ọgwụgwọ ọhụrụ maka ndị ọrịa buru ibu, ọkachasị ndị na-anabataghị nke ọma na usoro ndụ na-adabaghị maka ịwa ahụ bariatric. Usoro omume ya pụrụ iche na-enye echiche na ụzọ ọhụrụ maka ọgwụgwọ oke ibu, yana ọ nwere ike ịnwe uru karịa ọgwụ ịbelata ibu nke ọdịnala (D'Ascanio AM, 2024). Ihe ịga nke ọma nke ijikọta ọnụ nke Cagrilintide na semaglutide (CagriSema) na-egosi na ọgwụgwọ jikọtara ọtụtụ ebumnuche bụ atụmatụ dị irè iji meziwanye nzaghachi ọgwụgwọ maka oke ibu [6] . Ihe nlereanya a na-enye usoro ọhụrụ maka njikwa oke ibu ma na-ewetakwa nkwalite metabolic dị ukwuu na ndị ọrịa nwere ụdị ọrịa shuga 2.
Na mmechi, dị ka akwụkwọ akụkọ amylin analog nke na-eme ogologo oge, Cagrilintide nwere ikike dị ukwuu 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, ma ọ bụ naanị ya ma ọ bụ yana yana semaglutide, nwere ike belata ibu ahụ nke ọma ma na-anabata ya nke ọma. Tụkwasị na nke ahụ, ọ egosiwokwa ikike ịchịkwa glucose ọbara dị mma na ndị ọrịa nwere ụdị ọrịa shuga 2, na-enye nhọrọ ọgwụgwọ ọhụrụ maka ọgwụgwọ oke ibu na ọrịa shuga, na-ejuputa oghere na usoro ọgwụgwọ dị ugbu a, karịsịa maka ndị ọrịa na-adịghị anabata nke ọma na usoro ndụ na-adịghị mma maka ịwa ahụ. Usoro ọgwụgwọ ọtụtụ ebumnuche ya na-enye echiche 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 [4].
▎ Okwu ndị dị mkpa
[1] Hansen KE, Murali S, Chaves IZ, et al. Mmetụta Glycomacropeptide Amylin-Mediated Satiety, Postprandial Markers of Glucose Homeostasis, na Fecal Microbiome na Obese Postmenopausal Women[J]. Akwụkwọ akụkọ nke Nutrition, 2023,153 (7): 1915-1929.DOI: 10.1016 / j.tjnut.2023.03.014.
[2] Ling W, Huang Y, Qiao Y, et al. Amylin mmadụ: Site na Pathology gaa na Physiology na Pharmacology[J]. Protein & Sayensị Peptide dị ugbu a, 2019,20(9):944-957.DOI:10.2174/ 13892037206 66 19032811183 3.
[3] Kruse T, Hansen JL, Dahl K, et al. Mmepe nke Cagrilintide, Amylin Analogue na-eme ogologo oge[J]. Akwụkwọ akụkọ Chemistry ọgwụ, 2021,64 (15): 11183-11194.DOI: 10.1021/acs.jmedchem.1c00565.
[4] 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 ebebo na njikwa na-arụ ọrụ, usoro nchọpụta dose-2 nnwale [J]. Lancet, 2021,398 (10317):2160-2172.DOI:10.1016/S0140-6736(21)01751-7.
[5] D'Ascanio AM, Mullally JA, Frishman W H. Cagrilintide: Amylin Analog na-eme ogologo oge maka ọgwụgwọ oke ibu [J]. Ihe gbasara obi na nyocha, 2024,32 (1): 83-90.DOI: 10.1097/CRD.000000000000513.
[6] Frias JP, Deenadayalan S, Erichsen L, et al. Ịdị irè na nchekwa nke cagrilintide 2.4 mg otu ugboro kwa izu nwere semaglutide 2.4 mg otu ugboro n'izu na ụdị ọrịa shuga 2: multicentre, randomized, double-kpuru, na-arụsi ọrụ ike, usoro 2 ikpe [J]. Lancet, 2023,402 (10403):720-730.DOI:10.1016/S0140-6736(23)01163-7.
[7] Enebo LB, Berthelsen KK, Kankam M, et al. Safety, nnabata, pharmacokinetics, na pharmacodynamics nke concomitant nchịkwa nke otutu doses nke cagrilintide na semaglutide 2.4 mg maka ibu njikwa: a randomised, akara, usoro 1b ikpe [J]. Lancet, 2021,397 (10286): 1736-1748.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.