Los ntawm Cocer Peptides 
1 month ago
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.
1. Taw qhia
Kev rog rog tau dhau los ua kev txhawj xeeb rau pej xeem kev noj qab haus huv thoob ntiaj teb, ua rau muaj kev pheej hmoo ntawm ntau yam teeb meem xws li kab mob plawv thiab ntshav qab zib. Nrhiav cov tshuaj kho kev rog rog yog qhov tseem ceeb tshaj plaws. Survodutide, raws li ob tus agonist ua yeeb yam ntawm glucagon receptor (GCGR) thiab glucagon-zoo li peptide-1 receptor (GLP-1R), qhia tau hais tias muaj peev xwm loj hauv kev kho mob rog.
Daim duab 1 Cov teebmeem ntawm glucagon-zoo li peptide-1 (GLP-1), qabzib-dependent insulinotropic polypeptide (GIP), thiab glucagon ntawm ntau yam tseem ceeb hauv nruab nrog cev thiab cov ntaub so ntswg.
2. Txheej txheem cej luam ntawm Survodutide
2.1 Kev txhim kho keeb kwm yav dhau
Qhov tshwm sim thoob ntiaj teb ntawm kev rog thiab hom 2 mob ntshav qab zib mellitus (T2DM) tseem nce ntxiv, thiab cov tshuaj tiv thaiv kab mob ntshav qab zib feem ntau ua rau qhov hnyav nce, ua rau muaj kev xav tau sai rau cov kev kho tshiab uas tuaj yeem kho T2DM thiab rog ib txhij. GLP-1 receptor agonists (GLP-1 RAs) thiab dual GLP-1 / GIP receptor agonists tau pom tias muaj kev ua tau zoo hauv kev poob phaus thiab kev txhim kho metabolic, Survodutide (BI 456906) tau tshwm sim los ua tus neeg sib tw, ib tug ntev-ua yeeb yam dual agonist tam sim no nyob rau hauv kev tshawb nrhiav.
2.2 Lub Hom Phiaj Mechanism
Survodutide qhov tshwj xeeb yog nyob rau hauv nws lub peev xwm los ua kom GCGR thiab GLP-1R ib txhij. GCGR feem ntau tswj cov ntshav qabzib, txhawb nqa glycogenolysis thiab gluconeogenesis hauv lub siab thaum ua haujlwm, yog li ua kom cov ntshav qabzib nce siab. Hauv cov txheej txheem ntawm kev ua ntawm Survodutide, nws tsis tsuas yog nce ntshav qabzib tab sis hloov kho lub zog metabolism los ntawm kev sib koom ua ke nrog GLP-1R. GLP-1R yog dav faib nyob rau hauv ntau yam ntaub so ntswg thiab kabmob, nrog rau lub txiav, plab hnyuv, lub plawv, thiab hlwb. Ua kom GLP-1R txhawb kev tsim cov tshuaj insulin, inhibits glucagon secretion, qeeb plab hnyuv, ua rau kom satiety, yog li txo cov khoom noj thiab txo lub cev hnyav. Survodutide ua rau muaj kev cuam tshuam ntau dua ntawm cov kab mob metabolic los ntawm dual receptor agonism, pab kho kev rog.
3. Lub luag haujlwm ntawm Survodutide hauv Kev Kho Mob Obesity
3.1 Kev Tswj Xyuas Qhov hnyav
Ntau qhov kev tshawb fawb soj ntsuam tau pom tias Survodutide muaj qhov hnyav-txo cov nyhuv hauv cov neeg mob rog. Hauv Phase 2 kev sim tshuaj ntsuam xyuas cov neeg rog rog yam tsis muaj ntshav qab zib, 387 tus neeg koom nrog hnub nyoog 18 txog 75 xyoo nrog lub cev qhov hnyav (BMI) ≥27 kg / m² raug random muab 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. Thaum kawg ntawm 46 lub lis piam, tag nrho cov Survodutide koob tshuaj pab pawg pom qhov poob phaus, nrog rau 4.8 mg pab pawg ua tiav qhov hnyav ntawm qhov nruab nrab mus txog 18.7%. Los ntawm kev txheeb xyuas pawg neeg los ntawm poj niam txiv neej thiab BMI, cov poj niam tau pom tias qhov hnyav dua tom qab tau txais 4.8 mg ntawm Survodutide, nrog qhov hnyav nruab nrab ntawm -17.0%, thaum cov txiv neej muaj -11.9%. Ntawm cov pab pawg BMI sib txawv, cov neeg koom nrog BMI <30 kg/m² uas tau txais Survodutide 4.8 mg kev kho mob tau ntsib qhov poob phaus ntau tshaj plaws, nce mus txog -19.1%. Qhov no qhia tau hais tias Survodutide muaj qhov hnyav-txo cov neeg mob rog ntawm cov poj niam txiv neej sib txawv thiab qib BMI, nrog rau cov kev cuam tshuam ntau dua hauv qee pawg.
Daim duab 2 Lub Ntsiab Tseem Ceeb Kawg tom qab 48 Lub Limtiam ntawm Kev Npaj Kho Mob.
3.2 Qhov cuam tshuam rau lub cev muaj roj faib
Ntxiv nrog rau qhov poob tag nrho, Survodutide kuj tseem muaj txiaj ntsig zoo rau lub cev rog faib. Piv nrog rau cov placebo pab pawg, tag nrho cov tshuaj Survodutide pawg tau pom qhov txo qis ntawm lub duav ncig, nrog rau 4.8 mg pawg ua tiav qhov loj tshaj qhov nruab nrab txo ntawm 16.6 cm. Kev txo qis hauv lub duav ncig qhia txog kev txo qis hauv plab rog, uas cuam tshuam nrog kev pheej hmoo ntawm cov kab mob plawv. Qhov no qhia tias Survodutide tsis tsuas yog txo lub cev hnyav xwb tab sis kuj txhim kho lub cev muaj roj faib los ntawm kev txo cov rog hauv plab, yog li txo qis kev pheej hmoo ntawm kev rog rog ntsig txog kab mob plawv.
3.3 Kev txhim kho hauv metabolic tsis
Survodutide tsis tsuas yog tswj lub cev qhov hnyav, tab sis kuj muaj txiaj ntsig zoo ntawm ntau yam kab mob metabolic. Nyob rau hauv cov nqe lus ntawm lipid metabolism, thaum lub sij hawm kho, triglycerides (TG) txo qis nyob rau hauv tag nrho cov Survodutide pawg, thiab tsawg-density lipoprotein (VLDL) tsawg tsawg nyob rau hauv tag nrho cov tshuaj Survodutide pawg. LDL txo qis hauv pawg koob tshuaj 2.4 thiab 3.6 mg, thaum tag nrho cov cholesterol (TC) thiab cov cholesterol uas tsis yog HDL (non-HDL-C) txo qis hauv pawg 0.6, 2.4, thiab 3.6 mg. HDL tseem nyob ruaj khov thaum kho. Hais txog ntshav siab, hauv kev kho mob tiag tiag, Survodutide tuaj yeem txo cov ntshav siab systolic (SBP) txog li 10.2 mmHg thiab diastolic ntshav siab (DBP) los ntawm 4.8 mmHg, nrog cov txiaj ntsig zoo sib xws ntawm cov ntshav siab-txo qis tau pom tsis hais seb puas muaj ntshav siab ua ntej kuaj. Cov kev txhim kho hauv cov txheej txheem metabolic no pab txo qis kev pheej hmoo ntawm cov kab mob plawv hauv cov neeg mob rog rog, ntxiv rau Survodutide cov txiaj ntsig zoo hauv kev kho mob rog rog.
3.4 Mechanism of Action
Survodutide ua rau nws qhov hnyav poob los ntawm kev ua kom GCGR thiab GLP-1R. Kev ua haujlwm ntawm GLP-1R txhawb kev tsim cov tshuaj insulin, txhim kho kev nkag siab ntawm insulin, txo qis qab los noj mov, thiab txo cov zaub mov noj. Nws kuj tseem ncua lub plab khoob, ncua lub sij hawm cov zaub mov tseem nyob hauv plab thiab ntxiv satiety. Kev ua kom GCGR koom nrog kev tswj hwm kab mob siab los ntawm kev txhawb nqa cov roj oxidation thiab inhibiting rog synthesis, yog li txo cov rog hauv lub cev. Survodutide kuj tseem tuaj yeem cuam tshuam cov metabolism hauv lub zog thiab lub cev hnyav los ntawm kev tsis ncaj ncees xws li kev tswj lub plab microbiota.
4. Daim ntawv thov ntawm Survodutide hauv kev kho mob rog
4.1 Cov ntaub ntawv tshawb fawb soj ntsuam
Hauv kev tshawb fawb ntawm cov neeg mob uas muaj hom 2 mob ntshav qab zib thiab rog rog, Survodutide kuj pom tau tias muaj txiaj ntsig zoo hypoglycemic thiab poob phaus. Tom qab 16 lub lis piam ntawm kev kho mob, cov neeg mob hemoglobin A1c (HbA1c) qib tau txo qis, nrog qhov txo qis tshaj plaws ntawm 1.7%, thiab lub cev hnyav kuj txo qis, nrog rau qhov txo qis tshaj plaws ntawm 14.9%. Hauv kev tshawb fawb ntawm cov neeg mob nrog metabolic dysfunction-associated steatohepatitis (MASH) thiab rog rog, Survodutide tsis tsuas yog txhim kho daim siab histological cim tab sis kuj ua rau poob phaus hauv cov neeg mob. Cov kev tshawb fawb no tau lees paub qhov ua tau zoo ntawm Survodutide hauv ntau cov neeg uas muaj kev rog rog.
4.2 Kev sib piv zoo dua lwm yam tshuaj
Piv nrog rau cov tshuaj poob phaus, Survodutide muaj ntau yam zoo. Cov tshuaj yuag poob qis feem ntau tsom rau ib qho kev ua haujlwm, uas ua rau muaj kev ua tau zoo thiab muaj kev pheej hmoo siab dua. Survodutide, txawm li cas los xij, ua los ntawm dual receptor agonism, zoo txo lub cev hnyav thaum tib lub sijhawm txhim kho cov metabolism xws li ntshav qabzib, qib lipid, thiab ntshav siab, yog li muab kev tiv thaiv thiab kev kho mob rau cov teeb meem rog rog.
Piv rau lwm cov tshuaj poob phaus xws li semaglutide (GLP-1 receptor agonist), hauv kev sim tsiaj, ob qho tib si Survodutide thiab semaglutide ua rau poob phaus. Txawm li cas los xij, Survodutide nthuav tawm ntau qhov tshwj xeeb ntawm kev nyiam zaub mov thiab lipid txawv txav. Semaglutid txo qis kev noj zaub mov hauv cov theem pib ntawm kev kho mob tab sis rov qab mus rau theem pib tom qab, thaum Survodutide tsis tu ncua txo kev noj zaub mov muaj roj ntau thiab cov dej fructose hauv 5 lub lis piam. Hais txog lipid profiles, Semaglutid feem ntau txo qis tag nrho cov roj (cholesterol) los ntawm kev txo qis HDL-cholesterol, thaum Survodutide qhia txog kev txo cov roj cholesterol thoob plaws tag nrho cov lipoprotein Cheebtsam, suav nrog LDL-cholesterol. Qhov no qhia tau hais tias Survodutide tuaj yeem muab cov txiaj ntsig zoo tshaj plaws hauv kev tswj cov khoom noj thiab cov lipid profile.
5. Cov lus xaus
Survodutide, raws li tus tshiab dual agonist ntawm GCGR / GLP-1R, qhia tau hais tias muaj txiaj ntsig zoo hauv kev kho mob rog. Nws tsis tsuas yog ua kom lub cev hnyav thiab txhim kho lub cev muaj roj, tab sis kuj tswj hwm ntau yam kev cuam tshuam hauv metabolic xws li ntshav qabzib, ntshav lipids, thiab ntshav siab, muab ntau yam txiaj ntsig rau cov neeg mob rog rog.
Qhov chaw
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[4] Briand F, Augustin R, Bleymehl K, et al. 7279 Survodutide thiab Semaglutid Ob leeg ua rau poob phaus tab sis nthuav tawm qhov sib txawv ntawm kev nyiam noj zaub mov thiab dyslipidemia hauv Kev Xaiv Dawb Kev Noj Qab Haus Huv-induced Obese Hamster Model [J]. Phau ntawv Journal of the Endocrine Society, 2024,8(Supplement_1):bvae134-bvae163.DOI:10.1210/jendso/bvae163.034.
[5] Her MBU, Rosenstock J, Hoefler J, et al. koob tshuaj- teb cov teebmeem ntawm HbA1c thiab lub cev hnyav txo ntawm survodutide, dual glucagon / GLP-1 receptor agonist, piv nrog cov placebo thiab qhib-label semaglutide hauv cov neeg mob ntshav qab zib hom 2: kev sim tshuaj ntsuam xyuas randomized [J]. Diabetologia, 2023, 67: 470-482.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
