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. Txheej txheem cej luam
Slu-PP-332, ib qho hluavtaws estrogen receptor-related orphan receptor (ERR) agonist, tuaj yeem muaj txiaj ntsig zoo rau tib neeg kev noj qab haus huv hauv ntau txoj hauv kev. Los ntawm cov txheej txheem tshuaj lom neeg, nws belongs rau cov chav kawm tshwj xeeb ntawm cov khoom siv me me uas tuaj yeem khi rau ERR receptors, yog li ua kom muaj ntau cov lus teb ntawm lub cev. Tsis zoo li cov tshuaj ib txwm siv lossis txoj hauv kev rau kev tswj hwm lub cev ua haujlwm, Slu-PP-332 tawm dag zog lub cev los ntawm kev tsom mus rau qhov tshiab ERR receptor.
Daim duab 1 Cov qauv tshuaj ntawm Slu-PP-332.
2. Mechanism of Action
Kev Tswj Xyuas Lub Zog Metabolism: Slu-PP-332 nthuav tawm cov kev cai tseem ceeb ntawm lub zog metabolism. Nws qhib lub ERR receptor, txhim kho kev siv hluav taws xob. Nyob rau theem cellular, nws nce mitochondrial muaj nuj nqi thiab txhim kho cellular ua pa efficiency, ua kom cov hlwb hloov cov as-ham rau hauv lub zog ntau dua. Hauv cov nqaij pob txha pob txha, Slu-PP-332 induces qhia txog cov noob caj noob ces, txhawb fatty acid oxidation, cia cov rog yuav tsum tau siv tag nrho raws li ib tug lub zog qhov chaw thiab txo cov rog. Cov teebmeem no ua rau lub cev lub zog metabolism thaum lub sijhawm ua haujlwm, ua rau lub cev tswj hwm kev siv zog siab txawm tias thaum so, uas pab tswj lub cev hnyav thiab txhim kho tag nrho cov txheej txheem metabolic.
Txhim kho cov leeg pob txha ua haujlwm: Hais txog cov leeg pob txha, Slu-PP-332 qhia tau zoo. Nws tuaj yeem qhib qhov kev tawm dag zog aerobic genetic program, uas nyob ntawm ERRα receptor. Cov kev tshawb fawb tau pom tias tom qab siv Slu-PP-332 rau cov nas, muaj kev nce hauv hom IIa oxidative skeletal leeg nqaij fibers, uas txhim kho cov leeg nqaij. Hom IIa fibers muaj peev xwm oxidative ntau dua, ua kom muaj txiaj ntsig zoo dua ntawm kev siv oxygen los tsim lub zog, yog li ua kom cov leeg ua haujlwm ntev. Rau tib neeg, qhov no qhia tias Slu-PP-332 tuaj yeem pab txhim kho kev tawm dag zog, uas muaj txiaj ntsig zoo rau ob tus neeg ncaws pob nrhiav kev txhim kho kev ua tau zoo thiab cov tib neeg lub hom phiaj los txhim kho lub cev muaj peev xwm niaj hnub. Nws kev txhim kho ntawm cov pob txha pob txha mitochondrial muaj nuj nqi kuj tseem tuaj yeem pab txo qis cov leeg nqaij thiab ua kom rov qab ua haujlwm rov qab.
Kev kho mob plawv: Estrogen receptor-related orphan receptors ERRα thiab ERRγ yog cov tswj hwm tseem ceeb ntawm cov metabolism hauv plawv. Cov nas tsis muaj ERRα thiab ERRγ ua rau tuag taus cardiomyopathy thiab lub plawv tsis ua haujlwm. Raws li kev ua haujlwm zoo ERR agonist, Slu-PP-332 plays lub luag haujlwm tseem ceeb hauv kev tswj hwm lub plawv. Cov kws tshawb fawb tau ua rau lub plawv tsis ua haujlwm hauv cov neeg laus cov nas ntawm aortic coarctation (TAC) thiab tom qab ntawd muab Slu-PP-332 rau kev kho mob. Slu-PP-332 kev kho mob tau zoo txhim kho qhov ejection feem ntawm cov nas, qhov taw qhia tseem ceeb ntawm kev ua haujlwm ntawm lub plawv, qhia txog kev ua kom lub plawv dhia. Nws kuj tau txhim kho mitochondrial ultrastructure, txo cov hlab plawv, thiab normalize qhov txawv txav ntawm cov noob muaj feem xyuam. Cov kev hloov no sib sau ua ke los tswj lub plawv tus qauv thiab kev ua haujlwm. Slu-PP-332 qhov kev txhim kho hauv kev ua haujlwm ntawm lub plawv yog vim nws qhov kev txhim kho ntawm mitochondrial muaj nuj nqi thiab kev tswj hwm ntawm fatty acid metabolism txoj hauv kev, muab txoj hauv kev kho tshiab rau lub plawv tsis ua haujlwm.
3. Cov ntawv thov
Kev Ua Si Cov Tshuaj Kho Mob: Hauv cov tshuaj kis las, Slu-PP-332 tuav lub peev xwm zoo rau kev thov. Rau cov neeg ncaws pob, nws tuaj yeem ua haujlwm tshiab-txhim kho tus neeg sawv cev. Los ntawm kev txhim kho kev ua kom muaj zog thiab txo cov leeg leeg, cov neeg ncaws pob tuaj yeem ua tau zoo dua thaum kev cob qhia thiab kev sib tw. Cov neeg taug kev mus deb tuaj yeem ntsib qhov kev tawm dag zog ntev ntev thiab txhim kho kev sib tw ua haujlwm tom qab siv. Rau cov neeg nyiam kev noj qab haus huv, Slu-PP-332 tuaj yeem pab lawv ua tiav lub xeev muaj zog ntawm cov metabolism hauv lub cev thaum lub sijhawm ua haujlwm, txhim kho kev tawm dag zog, txo cov leeg mob tom qab qoj ib ce thiab lwm yam tsis xis nyob, thiab txhawb nqa lub cev rov qab, ua rau lawv koom nrog ntau dua hauv kev tawm dag zog thiab kev cob qhia. Rau cov neeg tsis tuaj yeem koom nrog kev tawm dag zog siab vim kev ua haujlwm tsis zoo ntawm lub cev, xws li cov neeg laus lossis cov neeg mob uas muaj qee yam kab mob ntev, Slu-PP-332 txhim kho cov leeg nqaij thiab lub zog metabolism, ua rau lawv koom nrog kev tawm dag zog thiab ua kom lawv lub neej zoo.
Kev kho cov kab mob metabolic: Hauv kev kho cov kab mob metabolic, Slu-PP-332 kuj pom muaj peev xwm tseem ceeb. Noj rog ua piv txwv, nws txhim kho kev siv hluav taws xob thiab txo cov rog, muab kev kho tshiab rau cov neeg mob rog. Cov kev tshawb fawb ua ntej qhia tau hais tias hauv kev noj zaub mov kom cov nas rog rog lossis ob / ob nas qauv, kev tswj hwm ntawm Slu-PP-332 ua kom lub cev hnyav thiab txhim kho insulin rhiab heev. Qhov no kuj tseem ceeb rau cov neeg mob ntshav qab zib hom 2, vim tias insulin tsis kam yog ib qho ntawm cov txheej txheem tseem ceeb ntawm cov kab mob ntshav qab zib hom 2. Slu-PP-332 txhim kho insulin rhiab heev, yog li pab tswj cov ntshav qabzib zoo dua. Rau cov tib neeg uas muaj cov kab mob metabolic, Slu-PP-332 tuaj yeem txhim kho ntau yam kab mob metabolic, xws li dyslipidemia thiab kub siab, yog li txo qhov kev pheej hmoo ntawm cov teeb meem xws li kab mob plawv.
4. Cov lus xaus
Kev tiv thaiv kab mob plawv thiab kev kho mob: Muab Slu-PP-332 cov txiaj ntsig zoo ntawm kev ua haujlwm ntawm lub plawv, nws tuav cov txiaj ntsig tseem ceeb hauv kev tiv thaiv kab mob plawv. Rau cov neeg mob plawv tsis ua hauj lwm, kev xaiv kho tam sim no raug txwv, tab sis Slu-PP-332 txhim kho lub plawv ua haujlwm los ntawm kev txhim kho mitochondrial muaj nuj nqi thiab tswj cov roj fatty acid metabolism, muab cov tshuaj tshiab rau kev kho mob plawv. Rau cov pej xeem uas muaj kev pheej hmoo ntawm kab mob plawv, xws li cov neeg mob ntshav siab lossis kab mob plawv, Slu-PP-332 tuaj yeem ua lub luag haujlwm tiv thaiv los ntawm kev tswj xyuas cov metabolism hauv plawv thiab ua haujlwm, yog li txo qhov kev pheej hmoo ntawm kab mob plawv. Nyob rau hauv cov ntsiab lus, Slu-PP-332, raws li ib tug compound nrog ib tug tshwj xeeb mechanism ntawm kev ua, tuaj yeem txhim kho lub cev ua haujlwm.
Qhov chaw
[1] Nasri H. Kev cia siab tshiab ntawm 'SLU-PP-332' ua tus neeg sawv cev zoo rau kev poob phaus nrog kev tiv thaiv lub raum tsis ncaj; nephrology point of view [J]. Phau ntawv Journal of Renal Endocrinology, 2024. https://api.semanticscholar.org/CorpusID: 267189187.
[2] Billon C, Sitaula S, Banerjee S, et al. A Synthetic ERR$alpha$ Agonist Induces a Acute Aerobic Exercise Response and Enhances Exercise Capacity [J]. Biorxiv, 2022. https://api.semanticscholar.org/CorpusID: 252819965.
[3] Xu W, Billon C, Li H, et al. Abstract 9682: Lub plawv tiv thaiv teebmeem ntawm Novel Synthetic Pan-Estrogen Related Receptor Agonists Slu-pp-332 thiab Slu-pp-915 [J]. Circulation, 2021,144.DOI:10.1161/circ.144.suppl_1.9682.
Cov khoom muaj rau kev tshawb fawb siv nkaus xwb:
