Glucagon zoo li peptide-1 (GLP-1)yog ib qho tshuaj hormone secreted los ntawm txoj hnyuv, uas tuaj yeem nkag mus rau hauv cov ntshav - lub hlwb thaiv thiab nkag mus rau peb lub hlwb hais kom ua haujlwm kom txo qis qab los noj mov; Ntawm qhov tod tes, nws tuaj yeem ua rau cov nqaij ntshiv ntawm lub plab zom mov thiab lub paj hlwb peripheral, ua rau lub plab zom mov qeeb thiab ua rau lub sijhawm zaub mov nyob hauv plab. Qhov no tsis tsuas yog pab txo cov ntshav qab zib hloov pauv, tab sis kuj tseem txhim kho satiety. Raws li qhov tshwm sim, GLP-1 tau dhau los ua lub hom phiaj lub hnub qub hauv kev poob phaus, ua tiav kev sib koom ua ke sab hauv thiab sab nraud. Nyob rau hauv xyoo tas los no, GLP-1 receptor agonists uas ua raws li tej yam ntuj tso GLP-1 tau txais kev paub dav dav hauv kev poob phaus.
Meanwhile, lwm lub plab zom mov,glucose dependent insulin-zoo li tso peptide (GIP), kuj tseem suav tias yog lub hom phiaj poob phaus, feem ntau tshwm sim ua "tus pab" ntawm GLP-1. Kev sib koom ua ke ntawm GIP receptors thiab GLP-1 receptors tuaj yeem ua lub luag haujlwm sib koom ua ke hauv kev tswj qhov hnyav, piv txwv li, hauv Suav teb, pom zoo GLP-1 / GIP dual receptor agonist. Tirzepatide hmoovtuaj yeem ua tiav qhov hnyav txog li 21%. Txawm li cas los xij, txawm hais tias qhov kev poob phaus tau txais kev txhawb nqa los ntawm kev siv Tirzepatide, tseem muaj ntau yam tsis meej pem txog kev sib koom ua ke ntawm GIP vim peb tsis nkag siab txog nws.
Dab tsi yog qhov zoo ntawm GLP-1 / GIP receptor dual agonists?
Kev tshawb fawb ib txwm qhia tias GLP-1 / GIP receptor dual agonists (xws li terzapitide API hmoov) nthuav tawm qhov hnyav thiab kev txhim kho metabolic feem ntau vim lawv txoj kev sib koom ua ke triple thiab ntau yam txiaj ntsig metabolic.
1, Dual lub hom phiaj synergistic nyhuv li
GLP-1 (glucagon like peptide-1) and GIP (glucose dependent insulinotropic polypeptide) are two important intestinal insulinotropic hormones in the human body, which complement each other by activating different receptors. GLP-1 mainly inhibits appetite, delays gastric emptying, and promotes insulin secretion; GIP enhances insulin sensitivity and promotes glucose uptake in adipose tissue. The synergistic effect of the two can produce a "1+1>2 "cov nyhuv, uas yog superior rau ib leeg GLP-1 agonist hauv kev poob phaus, txo cov ntshav qab zib, thiab txhim kho metabolic.
2, Kev txhim kho hauv kev poob phaus
Cov kev tshawb fawb soj ntsuam tau pom tias kev kho mob nrog tiltrotide rau 72 lub lis piam tuaj yeem ua tiav qhov hnyav nruab nrab ntawm 22.5% (kwv yees li 24 kilograms), uas yog qhov zoo dua li 16.0% ua tiav nrog.semaglutide. Qhov kev poob phaus zoo heev no tshwm sim los ntawm: ① muaj zog qab los noj mov (dual activation ntawm lub chaw noj zaub mov hypothalamic); ② Lub plab zom mov tseem ceeb dua; ③ Txhawb kev hloov pauv ntawm cov ntaub so ntswg adipose dawb rau cov ntaub so ntswg adipose xim av thiab ua kom muaj zog noj; ④ Txhim kho cov qauv ntawm plab microbiota thiab tsim lub voj voog zoo ntawm "qhov hnyav - txhim kho microbiota - txhim kho cov metabolism".
3, Ntau cov txiaj ntsig metabolic
Ntxiv nrog rau qhov poob phaus, GLP-1/GIP dual agonists tau qhia txog kev tiv thaiv hauv ntau lub cev: ① kab mob plawv - txo qhov kev pheej hmoo ntawm cov teeb meem mob plawv loj (MACE) los ntawm 20%; ② Daim siab - txhim kho tsis zoo - cawv steatohepatitis (NASH) thiab txo cov roj hauv siab; ③ Lub raum - Kev ncua lub raum kev ua haujlwm qeeb thiab txo qis cov zis tso zis; ④ Metabolic Syndrome - kev txhim kho ntawm cov ntsuas metabolic xws li ntshav qab zib, ntshav lipids, thiab ntshav siab.
Dab tsi yog qhov kev tshawb fawb tshiab ntawm GLP-1 / GIP receptor dual agonists?
Tsis ntev los no, ib daim ntawv luam tawm hauv Cell Metabolism tau qhia tias GIP receptors tau nthuav tawm hauv cov cheeb tsam tseem ceeb ntawm lub hlwb (xws li hypothalamic arcuate nucleus, nruab nrab eminence, thiab lwm yam) uas tswj kev qab los noj mov, tshwj xeeb tshaj yog nyob rau hauv oligodendrocytes nyob rau hauv nruab nrab eminence. Oligodendrocyte yog lub xovtooj tseem ceeb hauv lub hauv nruab nrab ntawm lub paj hlwb los tsim myelin sheath, thiab nws txoj haujlwm zoo ib yam li "cov txheej txheem rwb thaiv tsev" ntawm cov hlab ntsha axon, uas tuaj yeem ua kom lub paj hlwb ua haujlwm.
Nws tau pom tias ua kom GIP receptors ntawm oligodendrocytes tuaj yeem txhim kho lawv txoj sia nyob thiab ua haujlwm thiab txhawb nqa myelination ntawm neurons. Qhov tseem ceeb tshaj, qhov ua kom muaj GIP receptor qhib qhov "ceev channel" rau GLP-1 nkag mus rau hauv lub hlwb los ntawm ob lub tswv yim: ib qho yog txhawm rau nce vascular permeability thiab pab GLP-1 hla cov ntshav- hlwb teeb meem los ntawm nce - tswj VEGF-A qhia; Qhov thib ob, siv myelinated axons raws li cov channel, GLP-1 tuaj yeem nkag mus rau hauv lub hlwb ncaj qha mus rau txoj hauv kev neural, hla qhov kev txwv ntawm cov hlab ntsha hauv hlwb.
Cov kev sim tau lees paub tias GIP receptor agonist tuaj yeem txhim kho qhov kev faib tawm thiab kev tsom mus rau GLP-1 receptor agonist hauv cov cheeb tsam tseem ceeb ntawm lub hlwb ntawm kev noj qab haus huv. Qhov kev sib koom ua ke no ua rau muaj txiaj ntsig zoo rau kev noj qab haus huv ntawm GLP-1, thiab cov nyhuv no yog nyob ntawm qhov qhia thiab ua kom GIP receptor ntawm oligodendrocytes.
Tsis tas li ntawd, txoj kev tshawb no kuj tau nthuav tawm cov txheej txheem tshiab ntawm GLP-1 inhibiting qab los noj mov: vasopressin neurons nyob rau hauv hypothalamic paraventricular nucleus yog cov neeg nruab nrab tseem ceeb ntawm GLP-1 inhibiting qab los noj mov, thiab inhibiting nws cov haujlwm tuaj yeem tshem tawm qhov hnyav ntawm GLP-1.
Txhawm rau ua kom tiav, GIP tsis tsuas yog koom nrog kev tswj hwm cov metabolism, tab sis kuj tuaj yeem txhim kho qhov ua tau zoo thiab lub hom phiaj ntawm GLP-1 nkag mus rau hauv lub hlwb los ntawm kev txhim kho cov permeability ntawm cov ntshav-hlwb barrier thiab muab txoj hauv kev axonal, uas piav qhia vim li cas GLP-1 / GIP dual agonists yog superior rau ib leeg GLP-1 agonists hauv kev poob phaus. Qhov kev tshawb pom no muab lub hauv paus tseem ceeb theoretical rau kev tsim cov tiam tshiab ntawm cov tshuaj kho mob rau cov kab mob metabolic.
Nws txoj kev txhim kho yav tom ntej nyob qhov twg?
Kev vam meej ntawm GLP-1/GIP dual agonists tau tsav nthwv dej ntawm kev tshawb fawb thiab kev txhim kho rau ntau lub hom phiaj agonists. Tam sim no, GLP-1 / GIP / GCG triple receptor agonists (xws litshuaj ritaglutide) tau nkag mus rau theem III kev sim tshuaj thiab tau pom tias muaj txiaj ntsig zoo hauv kev poob phaus (28.7% poob ntawm 68 lub lis piam). Tsis tas li ntawd, cov ntaub ntawv sib txawv ntawm cov tshuaj noj kuj tseem tab tom tsim sai, uas yuav muab ntau txoj kev kho mob rau cov neeg mob rog rog thiab cov kab mob metabolic yav tom ntej.
Feem ntau, GLP-1 / GIP dual agonist tau ua tiav kev nce qib hauv kev poob phaus, txo cov piam thaj, kev tiv thaiv kab mob plawv thiab lwm yam los ntawm ob lub hom phiaj sib koom ua ke, dhau los ua qhov tseem ceeb hauv kev rog rog thiab kev kho mob ntshav qab zib hom 2. Ntawm qhov tod tes, peb lub tuam txhab GLP-1 / GIP receptor dual agonist raw cov ntaub ntawv tau ua tiav cov txiaj ntsig ntawm kev coj noj coj ua, txhim khu kev qha zoo, thiab tus nqi kom zoo dua.
Kev ua tau zoo: Peb siv peptide khoom-theem synthesis thev naus laus zis ua ke nrog cov kua chromatography-mass spectrometry (LC-MS) rau tag nrho cov txheej txheem zoo tswj, xyuas kom meej cov khoom purity ntau dua los yog sib npaug rau 99.5% thiab nruj impurity cov ntsiab lus tswj hauv qab 0.1%. Los ntawm lub hom phiaj kev hloov kho thev naus laus zis, peb tau ua tiav qhov kev sib xyaw ua ke ntawm GLP-1 thiab GIP ib ntus, nrog rau cov chaw ua haujlwm tsis zoo thiab ua haujlwm lom neeg zoo dua li ib tus agonist. Fatty acid side chain modification technology txuas ntxiv ib nrab -lub neej mus rau 7-10 hnub, ua tau raws li qhov kev thov rau cov qauv ua haujlwm ntev.
Cov Txheej Txheem Zoo: Peb tau dhau GMP daim ntawv pov thawj thiab tsim kom muaj tag nrho cov txheej txheem zoo traceability los ntawm cov khoom siv raw khoom, ntau lawm, tshuaj xyuas mus rau warehouses. Txhua batch ntawm cov khoom yog muab nrog ib tug tiav kev soj ntsuam daim ntawv qhia (COA), nrog rau cov cim tseem ceeb xws li HPLC purity, amino acid sequence tsom xam, huab hwm coj spectrometry molecular ceeb thawj, kev ntsuam xyuas endotoxin, thiab lwm yam.
Tus nqi ua tau zoo: Los ntawm cov txheej txheem kev ua kom zoo thiab loj- teev ntau lawm, peb tau ua tiav qhov txo qis dua 30% ntawm cov nqi raw khoom thaum tswj xyuas qhov zoo ib yam. Peb muab cov kev pabcuam customized uas tuaj yeem kho cov kab ke, hloov kho qhov chaw, thiab ntim cov ntsiab lus raws li cov neeg siv khoom xav tau, txhawb cov khoom siv tau yooj yim ntawm gram mus rau kilogram. Tsis tas li ntawd, peb muaj cov khoom siv dav dav uas ua kom cov khoom xa tuaj raws sij hawm thiab ua rau koj txoj kev tshawb fawb thiab kev loj hlob sai.
Los ntawm kev xaivXi'an Faithful BioTech Co., Ltd, koj tsis tsuas yog tau txais cov khoom zoo siab -cov ntaub ntawv zoo, tab sis kuj yog ib qho kev daws teeb meem uas suav nrog kev siv tshuab, zoo, nqi, thiab lwm yam. Peb kuj muab kev pabcuam siab tshaj plaws hauv kev pabcuam kev pabcuam. Tsis tas li ntawd, peb tau tsim kom muaj kev sib raug zoo ntawm kev sib raug zoo nrog ntau yam zoo-cov tuam txhab tshuaj, thiab peb cov khoom tau ua tiav rau ntau txoj haujlwm tshiab, ua kom muaj kev nplua nuj ntawm daim ntawv thov. Qhov no tuaj yeem pab tau sai sai ntawm koj qhov GLP-1 / GIP dual agonist project.
Tsis lees paub:Cov ntaub ntawv luam tawm ntawm lub vev xaib no los ntawm Is Taws Nem, tsis tau txhais hais tias lub vev xaib no pom zoo nrog nws cov kev xav lossis lees paub qhov tseeb ntawm cov ntsiab lus. Thov ua tib zoo saib kom paub qhov txawv. Tsis tas li ntawd, cov khoom muab los ntawm peb lub tuam txhab tsuas yog siv rau kev tshawb fawb tshawb fawb. Peb tsis muaj lub luag haujlwm rau qhov tshwm sim ntawm kev siv tsis raug. Yog tias koj txaus siab rau peb cov khoom, lossis muaj cov lus qhia tseem ceeb ntawm peb cov khoom lossis tsis txaus siab rau cov khoom tau txais, Thov hu rau peb ntawm Email: sales6@faithfulbio.com; Peb pab neeg tau cog lus los ua kom tiav kev txaus siab ntawm cov neeg siv khoom.