API-Drug Peptide Linaclotide: Kwaya don maganin hanji da ta'aziyya

Linaclotide shine peptide na cyclic wanda ya ƙunshi amino acid 14, uku daga cikinsu sune cysteines waɗanda ke samar da haɗin gwiwar disulfide.Linaclotide yana da alaƙa da tsarin tsarin peptides na guanylin da uroguanylin, waɗanda ke da alaƙa na halitta na mai karɓar guanylate cyclase C (GC-C).Ana bayyana mai karɓa na GC-C akan luminal surface na sel epithelial na hanji, inda yake daidaita fitar da ruwa da motsin hanji.Linaclotide yana ɗaure ga mai karɓa na GC-C tare da ƙaƙƙarfan alaƙa da ƙayyadaddun ƙayyadaddun bayanai, kuma yana kunna shi ta hanyar haɓaka matakan intracellular na cyclic guanosine monophosphate (cGMP).cGMP shine manzo na biyu wanda ke daidaita martanin salon salula daban-daban, irin su chloride da bicarbonate secretion, shakatawar tsoka mai santsi, da daidaita yanayin zafi.Linaclotide yana aiki a cikin gida a cikin sashin gastrointestinal, kuma baya shiga shingen jini-kwakwalwa ko rinjayar tsarin kulawa na tsakiya.Linaclotide kuma yana samar da metabolite mai aiki, MM-419447, wanda ke da nau'ikan magunguna iri ɗaya zuwa linaclotide.Dukansu linaclotide da metabolite ɗin sa suna da juriya ga lalatawar proteolytic ta enzymes na hanji, kuma galibi ana kawar da su ba canzawa a cikin feces (MacDonald et al., Drugs, 2017).

Ta hanyar kunna mai karɓa na GC-C, linaclotide yana ƙara fitar da ruwa a cikin lumen na hanji, wanda ke sassauta stool kuma yana sauƙaƙe motsin hanji.Linaclotide kuma yana rage jijiyar visceral hypersensitivity da kumburi da ke hade da ciwon hanji mai banƙyama (IBS) da sauran cututtuka na ciki.Linaclotide yana daidaita aikin tsarin juyayi na ciki da kuma nociceptors na colonic, waɗanda ke da ƙananan ƙwayoyin cuta waɗanda ke watsa alamun zafi daga gut zuwa kwakwalwa.Linaclotide yana rage bayyanar cututtukan da ke da alaka da ciwo, irin su abu P da calcitonin peptide mai alaka da kwayoyin halitta (CGRP), kuma yana ƙara yawan maganganun masu karɓa na opioid, wanda ke yin maganin analgesia.Linaclotide kuma yana rage sakin cytokines masu kumburi, irin su interleukin-1 beta (IL-1β) da ƙari necrosis factor alpha (TNF-α), kuma yana ƙara sakin cytokines masu kumburi, irin su interleukin-10 (IL). -10) da kuma canza yanayin haɓakar beta (TGF-β).Wadannan tasirin linaclotide suna inganta alamun maƙarƙashiya da ciwon ciki a cikin marasa lafiya tare da IBS ko maƙarƙashiya (Lembo et al., The American Journal of Gastroenterology, 2018).

An nuna Linaclotide yana da tasiri da kuma jurewa a cikin gwaje-gwaje na asibiti da yawa da suka shafi marasa lafiya tare da CC ko IBS-C.A cikin waɗannan gwaje-gwajen, linaclotide ya inganta halayen hanji, kamar mitar stool, daidaito, da cikawa;rage ciwon ciki da rashin jin daɗi;da ingantacciyar rayuwa da gamsuwar haƙuri.Linaclotide kuma ya nuna kyakkyawan bayanin martabar aminci, tare da gudawa shine mafi yawan abin da ya faru.Abubuwan da ke faruwa na zawo ya dogara da kashi kuma yawanci mai sauƙi zuwa matsakaici cikin tsanani.Sauran abubuwan da suka faru mara kyau sun kasance gabaɗaya kama da placebo ko ƙananan mitar.Babu wani mummunan bala'i ko mutuwar da aka danganta ga maganin linaclotide (Rao et al., Clinical Gastroenterology da Hepatology, 2015).