Los ntawm Cocer Peptides 
18 hnub dhau los
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam ntawm Triple Agonists
Nyob rau hauv xyoo tas los no, nrog rau kev sib sib zog nqus ntawm kev tshawb fawb mus rau hauv lub pathogenesis ntawm cov kab mob metabolic, kev loj hlob ntawm ntau lub hom phiaj agonist tshuaj tsom rau ntau yam tshuaj hormones receptors tau dhau los ua lub ntsiab lus kub. Retatrutid yog ib qho tshiab triple agonist ntawm cov piam thaj-dependent insulinotropic polypeptide (GIP), glucagon-zoo li peptide-1 (GLP-1), thiab glucagon (GC) receptors.
(1) Physiological Basis ntawm Hormone Receptor Function
GIP Receptor: GIP yog lub plab hnyuv insulin-secreting hormone secreted los ntawm K hlwb nyob rau hauv cov hnyuv, tso tawm sai sai tom qab noj mov. Raws li kev khi rau GIP receptor, GIP txhawb nqa cov tshuaj insulin secretion, thiab cov nyhuv stimulatory no yog cov piam thaj-dependant, txhais tau hais tias thaum cov ntshav qabzib nce siab, GIP txhim kho nws cov txiaj ntsig insulin-secreting, pab tswj cov ntshav qabzib. Tsis tas li ntawd, GIP koom nrog kev tswj hwm ntawm lipid metabolism, cuam tshuam rau kev sib txawv ntawm adipocytes thiab lipid tsub zuj zuj.
Fig. 1. Kev kho RETA lossis SEMA txo lub cev hnyav thiab txhim kho cov ntshav qabzib sai.a Feem pua ntawm cov kev hloov hauv lub cev hnyav los ntawm cov hauv paus ntsiab lus tau tshaj tawm. b, Epididymal dawb adipose cov ntaub so ntswg hnyav tau suav rau ntawm qhov kawg. c Cov ntshav qabzib yoo mov tau suav nrog hauv cov hauv paus ntsiab lus thiab thoob plaws qhov kev tshawb fawb ntawm lub sijhawm qhia txog lub sijhawm kawg. d Tumor engraftment lossis 'tumor take' tau tshaj tawm.
GLP-1 receptor: GLP-1 yog zais los ntawm plab hnyuv L hlwb thiab tseem muaj cov piam thaj-dependent insulinotropic effect, txhim kho insulin synthesis thiab tso tawm, inhibiting glucagon secretion, thiab txo cov piam thaj hauv siab. GLP-1 kuj tseem ncua kev ua pa ntawm plab, ua kom satiety, thiab yog li txo cov khoom noj. Nws muaj kev tiv thaiv thiab kev loj hlob ntawm pancreatic beta hlwb, pab tswj kev ua haujlwm ntawm pancreatic.
3. GC Receptor:
Tom qab khi rau GC receptor, glucagon feem ntau ua rau lub siab los ntawm kev txhawb nqa glycogenolysis thiab gluconeogenesis, yog li ua kom cov ntshav qabzib nce siab. Nyob rau hauv lipid metabolism, nws txhawb lipolysis, nce kev tso tawm thiab oxidation ntawm fatty acids rau lub zog. Nyob rau hauv cov xwm txheej zoo li qub, glucagon secretion yog inhibited thaum cov ntshav qabzib nce siab kom tswj cov piam thaj.
(2) Qhov zoo ntawm Triple Agonist Action
Raws li triple agonist, Retatrutid tuaj yeem ua rau tib lub sijhawm qhib cov receptors peb zaug, ua kom muaj kev sib koom ua ke. Los ntawm kev ua kom GIP thiab GLP-1 receptors, nws txhim kho cov piam thaj-dependent insulin secretion, txo cov ntshav qabzib ntau dua. Qhov nce satiety thiab ncua lub plab khoob vim yog GLP-1 receptor activation, nrog rau lipolysis txhawb nqa los ntawm GC receptor activation, sib sau ua ke rau kev tswj hwm qhov hnyav. Qhov ntau lub hom phiaj ntawm kev ua haujlwm no muab kev tswj hwm ntau dua ntawm ntau yam txheej txheem pathophysiological cuam tshuam nrog cov kab mob metabolic.
Mechanism of Action of Retatrutid in Metabolic Diseases
Cov kab mob metabolic yog ib chav kawm ntawm cov xwm txheej tshwm sim los ntawm kev cuam tshuam hauv cov txheej txheem metabolic hauv lub cev, suav nrog cov xwm txheej xws li ntshav qab zib, rog, thiab kab mob tsis muaj dej cawv. Retatrutid exerts nws cov teebmeem ntawm cov kab mob metabolic los ntawm nws qhov tshwj xeeb triple agonist zog.
(1) Mechanism of Action in Diabetes
Glucose Regulation: Retatrutid activates GIP thiab GLP-1 receptors, txhim kho cov piam thaj-dependent insulin secretion. Thaum cov ntshav qabzib nce siab, nws ua rau muaj txiaj ntsig zoo rau pancreatic beta hlwb kom tso cov tshuaj insulin, txhawb nqa cov piam thaj thiab siv, yog li txo cov ntshav qabzib. Los ntawm inhibiting glucagon secretion thiab txo cov piam thaj hauv siab, nws ntxiv stabilizes cov ntshav qabzib. Hauv kev sim tshuaj ntsuam xyuas nrog rau cov neeg mob ntshav qab zib hom 2, kev kho Retatrutid ua rau txo qis hauv cov ntshav qabzib yoo mov thiab postprandial.
Kev tiv thaiv ntawm pancreatic beta hlwb: Ua kom cov GLP-1 receptor tsis tsuas yog txhawb nqa cov tshuaj insulin, tab sis kuj muaj kev tiv thaiv thiab kev loj hlob ntawm pancreatic beta hlwb. Retatrutid tuaj yeem ua tiav qhov no los ntawm kev ua haujlwm tsis tu ncua ntawm GLP-1 receptor, ua rau qeeb ntawm beta cell apoptosis, nce lawv cov naj npawb thiab kev ua haujlwm, yog li txhim kho insulin secretion muaj peev xwm thiab tswj cov ntshav qabzib hauv lub sijhawm ntev.
(2) Mechanism ntawm kev txiav txim hauv kev rog
Kev tswj hwm lub zog: Retatrutid ua rau GLP-1 receptors, ncua lub plab zom mov, ua kom lub sijhawm khaws khoom noj hauv plab, ua kom satiety, thiab txo cov khoom noj. Nws tuaj yeem ua rau lub hauv nruab nrab lub paj hlwb los tswj kev qab los noj mov ntsig txog neurotransmitters, xws li inhibiting kev tso tawm ntawm orexin, ntxiv txo qis qab los noj mov, thiab yog li tswj kev noj qab haus huv.
Kev siv hluav taws xob ntau ntxiv: Kev ua kom lub zog ntawm GC receptor txhawb lipolysis, nce kev tso tawm thiab oxidation ntawm fatty acids rau lub zog tsim. Cov oxidation ntawm fatty acids muab lub zog rau lub cev, txo cov roj cia, thiab pab kom poob phaus. Kev ua kom muaj GIP receptor kuj koom nrog kev tswj hwm lub zog metabolism, nce kev siv hluav taws xob.
Daim duab 2 Kev kho RETA txo lub cev hnyav thiab adiposity, txhim kho cov ntshav qabzib sai. Ib feem pua ntawm cov kev hloov pauv hauv lub cev qhov hnyav los ntawm qhov pib tau tshaj tawm. b Epididymal dawb adipose cov ntaub so ntswg tau hnyav ntawm qhov kawg thiab normalized rau tag nrho lub cev hnyav. c Cov ntshav qabzib yoo mov tau suav nrog hauv cov hauv paus ntsiab lus thiab thoob plaws qhov kev tshawb fawb ntawm lub sijhawm qhia txog lub sijhawm kawg.
(3) Mechanism of action in non-alcoholic fatty liver disease
Txhim kho hepatic lipid metabolism: Retatrutid activates GC receptor, txhawb kev tawg thiab β-oxidation ntawm cov rog hauv daim siab, yog li txo cov rog hauv daim siab. Kev ua kom lub GIP thiab GLP-1 receptors tuaj yeem tswj cov kev qhia ntawm cov noob muaj feem xyuam rau lipid metabolism hauv lub siab, txhim kho kev nthuav qhia ntawm fatty acid transporters thiab fatty acid oxidases, yog li txhawb cov fatty acid uptake thiab oxidation, thiab ntxiv txhim kho hepatic lipid metabolism.
Txhim kho cov tshuaj insulin rhiab heev: Thaum txhim kho kev tswj cov piam thaj thiab nce insulin secretion, Retatrutid tuaj yeem txhim kho lub siab insulin rhiab heev los ntawm kev ua kom GLP-1 receptors. Txhim kho cov tshuaj insulin rhiab heev txhim kho lub siab cov lus teb rau insulin, zoo dua inhibiting hepatic qabzib tso zis, txo de novo fatty acid synthesis, thiab li no alleviating hepatic steatosis.
Kev siv thiab cuam tshuam ntawm Retatrutid hauv Cov Kab Mob Metabolic
(1) Kev siv rau cov ntshav qab zib
lycemic Control Effects: Retatrutid qhia txog kev tswj glycemic tseem ceeb hauv cov neeg mob ntshav qab zib hom 2. Raws li cov ntaub ntawv, cov neeg mob kho nrog Retatrutid pom qhov txo qis hauv hemoglobin A1c (HbA1c). Hauv kev sim ntsuas randomized nrog 353 tus neeg mob uas muaj ntshav qab zib hom 2, qib HbA1c hauv pab pawg kho Retatrutid txo qis los ntawm 1.64% los ntawm qhov pib, thaum tsis muaj kev hloov pauv tseem ceeb hauv pawg placebo.
Kev sib piv nrog Lwm Cov Tshuaj: Muab piv nrog cov tshuaj tiv thaiv kab mob ib txwm muaj xws li metformin lossis GLP-1 receptor agonists, Retatrutid ua kom pom kev tswj ntshav qabzib zoo dua.
(2) Kev siv rau kev rog
Cov teebmeem poob phaus: Retatrutid qhia tau tias muaj txiaj ntsig zoo hauv kev kho mob rog. Hauv kev sim tshuaj ntsuam xyuas cov neeg mob rog rog, qhov hnyav hnyav tau pom tom qab 48 lub lis piam ntawm kev kho mob nrog ntau koob tshuaj Retatrutid. Hauv ib qho kev sim, cov neeg mob tau kho nrog 12mg koob ntawm Retatrutid tau ntsib qhov hnyav nruab nrab ntawm 24.2% tom qab 48 lub lis piam, piv rau tsuas yog 2.1% hauv pawg placebo. Tsis tas li ntawd, 83% ntawm cov neeg koom nrog hauv pab pawg neeg tau txais txiaj ntsig tau poob qis ntawm 15% lossis ntau dua, tshaj li 2% tus nqi hauv pawg placebo.
Lub Sij Hawm Ntev: Retatrutid tswj qhov hnyav poob zoo nyob rau lub sijhawm kho. Qhov no qhia tias kev siv mus sij hawm ntev tuaj yeem pab tswj qhov hnyav thiab tiv thaiv qhov hnyav rov qab, uas yog qhov zoo rau kev tswj kev rog mus ntev.
(3) Kev siv rau hauv cov kab mob uas tsis yog-alcoholic fatty siab
Kev txo cov rog hauv lub siab: Hauv cov neeg mob uas muaj cov kab mob metabolic-uas cuam tshuam nrog cov kab mob siab rog thiab lub siab rog cov ntsiab lus ≥10%, Kev kho Retatrutid ua rau txo qis hauv daim siab cov rog. Hauv kev sib piv, ob qhov muag tsis pom kev, kev sim tshuaj placebo, ntawm 24 lub lis piam, lub siab rog cov ntsiab lus tau txo qis los ntawm 81.4% thiab 82.4% los ntawm cov hauv paus hauv pawg 8 mg thiab 12 mg koob, raws li, thaum pawg placebo nce los ntawm tsuas yog 0.3%.
Qhov zoo thiab muaj peev xwm ntawm Triple Agonist
Retatrutid tau tswj hwm ntau txoj hauv kev pathophysiological ntawm cov kab mob metabolic los ntawm kev ua kom GIP, GLP-1, thiab GC receptors. Los ntawm kev tswj ntshav qabzib, tswj qhov hnyav, txhawm rau txhim kho hepatic lipid metabolism, qhov ntau lub hom phiaj ntawm kev ua haujlwm theoretically muab kev kho ntau dua ntawm cov kab mob metabolic piv rau cov tshuaj ib hom phiaj, ua kom pom qhov muaj peev xwm los daws qhov nyuaj etiology ntawm cov kab mob metabolic. Cov ntaub ntawv kuaj mob uas twb muaj lawm qhia tau tias Retatrutid tau ua tiav cov txiaj ntsig tseem ceeb hauv kev kho cov kab mob metabolic xws li ntshav qab zib, rog rog, thiab kab mob tsis muaj dej cawv.
Xaus
Raws li tus tshiab triple agonist, Retatrutid tuav cov lus cog tseg rau kev kho mob ntawm cov kab mob metabolic.
Qhov chaw
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Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
