Los ntawm Cocer Peptides 
29 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.
Thoob plaws ntiaj teb, kev rog rog tau dhau los ua qhov teeb meem kev noj qab haus huv loj zuj zus, txuas nrog ntau yam kab mob ntev xws li kab mob plawv thiab ntshav qab zib hom 2, ua rau kev tshawb fawb txog kev poob phaus zoo yog qhov tseem ceeb ntawm kev tshawb fawb kho mob. Survodutide, raws li cov tshuaj tshiab, tau pom tias muaj peev xwm ua tau zoo hauv kev poob phaus.
Txheej txheem cej luam ntawm Survodutide
Survodutide yog ib qho kev tshawb nrhiav ntev-ua yeeb yam dual agonist uas ib txhij tsom rau glucagon-zoo li peptide-1 receptor (GLP-1R) thiab cov piam thaj-dependent insulinotropic polypeptide receptor (GIPR). Nws tsuas yog xav tau kev tswj hwm ib zaug ib lub lim tiam, muab cov neeg mob yooj yim dua thiab txhim kho kev ua raws li kev kho mob mus ntev.
Mechanism ntawm Survodutide hauv Poob Poob
Regulating Energy Intake
Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv: Tom qab ua kom muaj GLP-1R thiab GIPR, Survodutide cuam tshuam nrog lub hauv paus paj hlwb los tswj lub chaw tswj kev noj qab haus huv hypothalamic. Kev ua haujlwm ntawm GLP-1R ua rau vagal afferent fibers kom xa cov teeb liab mus rau arcuate nucleus ntawm hypothalamus, inhibiting cov haujlwm ntawm agregp protein (AgRP) neurons, Nws tseem tuaj yeem qhib proopiomelanocortin (POMC) neurons, yog li ua rau muaj kev nkag siab ntawm satiety thiab txo cov khoom noj. Kev ua kom GIPR kuj tseem tuaj yeem txhim kho qhov qab los noj mov los ntawm txoj hauv kev zoo sib xws lossis kev sib koom ua ke ntawm neural, yog li txo lub cev xav tau zaub mov thiab ua rau txo qis zog.
Hloov cov zaub mov nyiam: Hauv hamster qauv ntawm kev rog thiab dyslipidemia vim yog kev noj zaub mov dawb, Survodutide tau ua rau muaj kev cuam tshuam tshwj xeeb rau kev nyiam zaub mov. Piv nrog rau pawg tswj hwm, Survodutide txo qis kev noj zaub mov muaj roj ntau thiab cov dej fructose-nplua nuj thaum lub sijhawm kho 5 lub lis piam, thaum tsis muaj kev cuam tshuam rau kev noj zaub mov tsis tu ncua thiab dej ib txwm muaj. Qhov kev tswj hwm ntawm kev xaiv zaub mov no pab txo qis cov khoom noj uas muaj calorie ntau ntau, tswj xyuas lub zog ntau dhau ntawm nws qhov chaw thiab tso lub hauv paus rau kev poob phaus.
Tswj kev siv hluav taws xob
Txhawb kom muaj roj oxidation: Survodutide nthuav tawm cov kev cai tseem ceeb ntawm cov roj metabolism. Los ntawm kev ua kom GLP-1R thiab GIPR, nws cuam tshuam cov roj cell metabolism los ntawm ntau txoj hauv kev qhia. Nws txhawb nqa lipolysis hauv adipocytes, nce kev tso tawm ntawm fatty acids; Cov roj ntsha uas tso tawm no raug thauj mus rau mitochondria rau oxidation, yog li nce kev siv hluav taws xob. Cov kev tshawb fawb tau pom tias nyob rau hauv cov qauv hauv vitro adipocyte, tom qab kev kho Survodutide, cov enzymes tseem ceeb koom nrog hauv lipolysis thiab fatty acid oxidation, xws li cov tshuaj hormone-sensitive lipase (HSL), carnitine palmitoyltransferase-1 (CPT-1), qhia tias nws cov txheej txheem ntawm kev ua haujlwm hauv kev txhawb nqa cov roj oxidation cuam tshuam nrog kev tswj cov roj metabolism.
Kev siv hluav taws xob ntau ntxiv: Ntxiv rau kev ua haujlwm ncaj qha ntawm cov roj ntsha los txhawb cov roj oxidation, Survodutide kuj tseem tuaj yeem nce kev siv hluav taws xob los ntawm kev cuam tshuam lub zog metabolism. Hauv kev sim tsiaj, nws tau pom tias thaum lub sijhawm ua haujlwm ntawm cov tsiaj tsis hloov pauv ntau tom qab kev tswj hwm Survodutide, lawv cov basal metabolic tus nqi nce. Qhov no yog vim cov tshuaj muaj txiaj ntsig zoo rau ntau cov ntaub so ntswg thiab lub cev, txhim kho cov metabolism hauv lub siab thiab cov leeg pob txha, yog li ua kom lub zog noj hauv lub xeev so thiab ua tiav lub zog tsis txaus, uas txhawb kev poob phaus.
Kev tswj hwm ntawm cov piam thaj metabolism thiab insulin rhiab heev
Txhim kho insulin tsis kam: Cov neeg rog rog feem ntau muaj cov tshuaj insulin tsis kam, uas cuam tshuam rau cov metabolism hauv lub zog thiab kev siv. Survodutide activates GLP-1R los txhawb cov insulin secretion thaum txhim kho cov tshuaj insulin, yog li ua rau lub cev ua haujlwm rau insulin. Hauv kev tshawb fawb ntawm cov neeg mob ntshav qab zib hom 2, tom qab 16 lub lis piam ntawm kev kho Survodutide, plasma insulin ntau ntau thiab cov tshuaj insulin tsis kam (HOMA-IR) tau txo qis, qhia tias cov tshuaj tuaj yeem txhim kho cov tshuaj insulin, ua kom cov cellular uptake thiab siv cov piam thaj, txo nws txoj kev hloov mus rau rog, thiab pab tswj qhov hnyav.
Kev tswj cov ntshav qabzib ntau: Survodutide's dual receptor agonist qhov ua rau nws muaj txiaj ntsig zoo hauv kev tswj cov ntshav qabzib. GLP-1R agonism txhawb nqa insulin secretion thaum inhibiting glucagon tso tawm, yog li txo cov ntshav qabzib. GIPR agonism kuj tseem txhawb nqa cov tshuaj insulin tso tawm hauv lub cev. Los ntawm kev sib koom ua ke, nws tuaj yeem tswj cov ntshav qabzib kom ruaj khov. Cov piam thaj hauv ntshav ruaj khov pab txo qis kev tshaib kev nqhis thiab nce lub zog cia los ntawm cov ntshav qab zib hloov pauv, ua rau muaj txiaj ntsig zoo rau kev tswj qhov hnyav.
Lub luag hauj lwm ntawm Survodutide hauv Poob Poob
Kev poob ceeb thawj tseem ceeb: Hauv kev sib piv, ob qhov muag tsis pom, placebo-tswj Phase 2 koob tshuaj nrhiav kev sim tsom rau cov neeg mob rog, 387 cov neeg laus hnub nyoog 18-75 xyoo nrog lub cev qhov hnyav (BMI) ≥27 kg / m² thiab tsis muaj ntshav qab zib tau muab faib rau tsib pawg, tau txais kev txhaj tshuaj subcutaneous txhua lub lim tiam ntawm Survodutide (0.6, 2.4, 3.6, lossis 4.8 mg) lossis placebo rau 46 lub lis piam kho. Cov txiaj ntsig tau pom tias nyob rau lub lim tiam 46, cov neeg mob kho nrog 4.8 mg ntawm Survodutide tau ntsib qhov hnyav nruab nrab ntawm 18.7% piv rau pawg placebo, nrog qhov sib txawv tseem ceeb hauv kev txo qhov hnyav. Hauv lwm txoj kev tshawb fawb tsom rau cov neeg mob ntshav qab zib hom 2 thiab rog rog, kev kho mob Survodutide tau ua rau poob phaus uas yog nyob ntawm koob tshuaj tom qab 16 lub lis piam, nrog qhov txo qis tshaj plaws ntawm 8.7%. Tsis tas li ntawd, Survodutide ntawm koob tshuaj ≥1.8 mg ib zaug ib lub lim tiam ua rau poob phaus ntau dua li GLP-1 receptor agonist Semaglutid uas nquag siv, uas ua rau qhov hnyav ntawm 5.3%.
Qhov sib txawv ntawm poj niam txiv neej thiab BMI: Cov kev tshawb fawb ntxiv tau qhia tias qhov hnyav poob ntawm Survodutide sib txawv ntawm cov poj niam txiv neej sib txawv thiab qib BMI. Hauv qhov kev sim hais saum toj no tsom rau cov neeg mob rog rog, nyob rau lub lim tiam 46, qhov nruab nrab qhov hnyav feem pua (17.0%) hauv 4.8 mg Survodutide pawg tau siab dua rau cov poj niam dua li cov txiv neej (11.9%); thoob plaws pawg BMI sib txawv, cov neeg mob uas BMI <30 kg/m² muaj qhov poob qis dua feem pua (19.1%), tab sis qhov hnyav poob qhov tseem ceeb tsis txawv txav ntawm BMI pawg. Qhov no qhia tau tias hauv kev kho mob, cov kws kho mob tuaj yeem kwv yees qhov hnyav dua ntawm Survodutide raws li cov xwm txheej xws li poj niam txiv neej thiab BMI.
Lub cev Fat Distribution thiab metabolic txhim kho
Txo cov roj visceral: Survodutide tsis tsuas yog txo tag nrho lub cev qhov hnyav, tab sis kuj muaj kev cuam tshuam zoo rau lub cev rog. Kev sib sau ntau dhau ntawm cov roj visceral yog cuam tshuam nrog kev loj hlob ntawm ntau yam kab mob metabolic. Hauv cov kev tshawb fawb cuam tshuam, tom qab tau txais kev kho mob Survodutide rau ib lub sijhawm, cov neeg mob tau ntsib qhov txo qis hauv visceral rog. Qhov no yog vim hais tias cov tshuaj txhawb kev tawg thiab oxidation ntawm cov roj visceral, txhim kho nws cov metabolism thiab yog li txo cov kev pheej hmoo metabolic cuam tshuam nrog cov roj visceral ntau dhau.
Txhim kho lipid abnormalities: Cov neeg mob rog rog feem ntau muaj lipid txawv txav, xws li hypercholesterolemia thiab hypertriglyceridemia. Survodutide tsis tsuas yog pab kom poob phaus, tab sis kuj txhim kho lipid tsis. Hauv kev sim tsiaj, rog hamsters kho nrog Survodutide pom qhov txo qis hauv plasma tag nrho cov roj cholesterol, nrog rau 41% txo qis hauv pab pawg Survodutide thiab 24% txo qis hauv pawg semaglutide. Cov txiaj ntsig zoo sib xws tau pom hauv tib neeg kev sim, qhov twg Survodutide kev kho mob ua rau txo qis hauv qib triglyceride. It also exerted varying degrees of regulatory effects on low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), helping to correct dyslipidemia and reduce the risk of cardiovascular disease.
Kev cuam tshuam rau cov kab mob plawv
Txo cov ntshav siab: Kev rog rog yog ib qho tseem ceeb ntawm kev pheej hmoo rau ntshav siab. Hauv kev sim tshuaj ntsuam xyuas cov neeg mob rog rog, tom qab 46 lub lis piam ntawm kev kho mob Survodutide, ob qho tib si systolic ntshav siab (SBP) thiab diastolic ntshav siab (DBP) pom qhov txo qis. Piv nrog rau cov placebo pab pawg, 4.8 mg Survodutide pawg tau pom qhov txo qis tshaj plaws ntawm 10.2 mmHg hauv SBP thiab 4.8 mmHg hauv DBP. Qhov kev txo qis ntshav siab no tuaj yeem cuam tshuam nrog ntau yam, suav nrog Survodutide kev txhim kho vascular endothelial muaj nuj nqi, txo qis kev ua haujlwm ntawm lub paj hlwb, thiab kev poob phaus, uas ua ke pab txo qis kev pheej hmoo ntawm cov kab mob plawv.
Txhim kho vascular muaj nuj nqi: Survodutide kuj tseem tuaj yeem tiv thaiv kev tiv thaiv ntawm cov hlab plawv los ntawm kev txhim kho kev ua haujlwm ntawm vascular endothelial hlwb. Tom qab kev tswj hwm Survodutide, tso tawm nitric oxide (NO) los ntawm vascular endothelial hlwb nce. TSIS yog ib qho tseem ceeb vasodilator uas nthuav cov hlab ntsha, txo cov hlab ntsha, thiab txhim kho cov ntshav ncig. Cov tshuaj kuj tseem tuaj yeem cuam tshuam cov lus teb inflammatory thiab oxidative kev nyuaj siab, yog li txo cov phab ntsa vascular puas thiab ntxiv kev noj qab haus huv vascular.
Daim ntawv thov ntawm Survodutide hauv Kev poob phaus
Lub Hom Phiaj
Cov neeg rog rog thiab rog rog: Rau cov neeg rog rog lossis rog rog nrog BMI ≥ 27 kg / m², Survodutide tau pom tias muaj txiaj ntsig zoo yuag. Ob tus neeg mob uas muaj kev rog yooj yim thiab cov neeg rog rog nrog rau lwm cov kab mob metabolic xws li ntshav qab zib hom 2 lossis dyslipidemia tuaj yeem tau txais txiaj ntsig los ntawm kev kho Survodutide. Hauv kev sim tshuaj, cov neeg mob rog rog thoob plaws ntau pawg hnub nyoog (18-75 xyoo) tau pom cov lus teb zoo rau Survodutide, qhia txog ntau yam ntawm cov neeg tsim nyog.
Cov neeg mob rog rog muaj feem xyuam rau cov kab mob tshwj xeeb: Ntxiv rau cov neeg rog rog, Survodutide kuj yog ib qho kev kho mob rau kev rog rog los ntawm cov kab mob tshwj xeeb, xws li polycystic zes qe menyuam syndrome (PCOS), qhov twg rog thiab cov kab mob metabolic feem ntau ua ke.
Txhawm rau txhim kho qhov hnyav ntxiv thiab txhim kho cov txheej txheem metabolic, Survodutide tuaj yeem siv ua ke nrog lwm txoj kev kho mob. Thaum ua ke nrog kev cuam tshuam hauv kev ua neej (kev tswj kev noj zaub mov thiab kev tawm dag zog), kev sib koom ua ke tuaj yeem ua tiav. Hauv kev sim tshuaj, cov neeg mob uas tau txais kev kho mob Survodutide ua ke nrog kev tawm dag zog tsis tu ncua thiab kev noj zaub mov zoo tau ntsib kev poob phaus ntau dua thiab kev txhim kho tseem ceeb hauv cov cim metabolic. Tsis tas li ntawd, rau cov neeg mob ntshav qab zib hom 2 thiab rog rog, Survodutide tuaj yeem siv ua ke nrog lwm cov tshuaj tiv thaiv kab mob xws li metformin los tswj cov ntshav qab zib thaum ua tiav kev tswj hwm qhov hnyav.
Xaus
Hauv cov ntsiab lus, Survodutide, raws li ib qho tshiab dual receptor agonist, yog qhov zoo rau kev poob phaus. Nws cov txheej txheem tshwj xeeb ntawm kev ua haujlwm tsis yog tsuas yog txo qhov hnyav xwb tab sis kuj txhim kho lub cev muaj roj faib, tswj cov piam thaj thiab lipid metabolism, thiab txo cov kev pheej hmoo ntawm cov hlab plawv.
Qhov chaw
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Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
