SR9011 Hmoovyog kev tshawb fawb compound, teej tug rau rev-erepta recept agonist qeb. Nws tsuas yog lub hom phiaj thiab tswj cov kev qhia ntawm cov noob muaj feem cuam tshuam nrog lub moos txheeb. Nyob rau hauv nws daim foos hmoov, nws yog ib feem siv hauv kev kuaj tshawb fawb thiab muaj tej zaum cov kev tswj hwm kev cuam tshuam ntawm cov metabolism hauv cov metabolism, tshuaj tiv thaiv cov tub rog. Cov kev tshawb fawb tau pom tias SR9011 tuaj yeem inhibit lub bmal1 thiab cov moos circarian thiab lipid metabolism thiab lipid metabolism thiab cov peev xwm txhim kho kev rog thiab mob ntshav qab zib. Tsis tas li ntawd, nws tau pom tias muaj kev xaiv tus ntxhiab tsw qab, tab sis muaj cov tshuaj lom tsawg rau cov hlwb ib txwm muaj. Sau ntawv: SR9011 tseem tsis tau pom zoo rau tib neeg siv thiab tsuas yog rau kev tshawb fawb. Nws lub sij hawm muaj kev nyab xeeb ntev, kev ua tshuaj, thiab cov kev mob tshwm sim tseem yuav tsum tau kawm ntxiv. Cov neeg siv yuav tsum nruj ua raws cov txheej txheem kev kuaj xyuas thiab tsis txhob muaj kev txwv tsis pub lossis sib chwv nrog cov khaub ncaws me me. Thaum kev yuav khoom, xaiv cov npe rov qab los xyuas kom paub meej thiab ua tau zoo, thiab ua raws li cov kev cai muaj nyob rau hauv qhov chaw tsaus). Tam sim no, cov kev tshawb fawb tus nqi ntawm SR9011 yog feem ntau muaj cov kab mob ntawm cov kab mob metabolic thiab cov tshuaj xyuas, tab sis cov ntawv thov tshawb fawb, tab sis cov ntawv thov kev nrhiav chaw nyob yuav tsum tau lees paub.
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Sr9011 Hmoov COA
Cov Lus Qhia Txuj Ci
SR9011 Hmoov yog ib qho khoom siv dag ntxias nuclear receptor rev-erb / agonist. Nws cov tshuaj lom neeg lub npe yog 3 - [[[[[[(4-chlorophenyl) [(5-pyrrolidinamide, nrog molecular hnyav ntawm 479.04 g / mol. Nws cov qauv tshuaj muaj cov pab pawg tseem ceeb xws li lub nplhaib thienyl, cov pab pawg pyrrolidine, thiab chlorophenyl pab pawg, uas suav txiav txim siab nws cov kev ua haujlwm.
Lub cev thiab tshuaj
Cov tsos thiab daim ntawv
SR9011 hmoov feem ntau yog cov xim dawb rau lub teeb daj daj nrog lub purity ntau tshaj li 98% (kuaj pom los ntawm HPLC). Cov khoom siv siab tshaj plaws yog qhov tseem ceeb rau kev ntseeg tau ntawm kev sim sim, tshwj xeeb hauv xov tooj ntawm tes thiab cov kev sim tsiaj.
So
DMOs (Dimethyl sulfoxide): solubility yog 2 mL / mL (daws teeb meem meej), thiab nws yog cov kuab tshuaj uas ib txwm siv hauv chav kuaj.
Ethanol: Solubility yog qhov tseem ceeb, tab sis cov nqi tshwj xeeb txawv nyob ntawm tus neeg xa khoom.
Dej: Nws yog yuav luag tsis tau npaj thiab xav tau npaj raws li kev daws teeb meem ua haujlwm nrog tus pab cuam (xws li DMOPS lossis ethanol).
Chloroform, methanol: ib nrab soluble, tab sis kev sib cais ua hauj lwm qis dua li ntawm DMO.
Ruaj Thiab Cia
Cov lus luv luv luv: nws raug pom zoo kom khaws cia ntawm -20℃hauv tub yees kom tsis txhob rov qab khov thiab yaj.
Lub sijhawm ntev cia: nws yuav tsum tau muab ntim thiab tiv thaiv los ntawm lub teeb kom tiv thaiv oxidation thiab duraliquescence.
Kev mob thauj: feem ntau ntim nrog cov dej khov xiav lossis dej khov kom qhuav kom ntseeg tau qhov kub khov.
Lwm lub cev tsis
Ntws: kwv yees li 1.3 g / cm³ (kwv yees tus nqi).
Bushing taw tes: 642.8℃(kwv yees tus nqi, hauv qab 760 hli ntuj).
Flash point: 342.6 Degree (kwv yees tus nqi).
Refacking Qhov ntsuas: 1.595 (kwv yees tus nqi).
Acidity coefficient (PKA): 14.71 (kwv yees tus nqi).
Cov Khoom Siv Biochemical
SR9011 yog cov agonist muaj zog ntawm rev-erb / nuclear receptors. Nws cov tshuab ntawm kev ua yog raws li hauv qab no:
Rev-ERB: ic₅₀=790 ni}}}}}}} ibriting kev ua haujlwm puv nkaus).
Rev-ERB: ic₅₀=560 ni}}}}}}} ibriting kev ua haujlwm puv nkaus).
Los ntawm kev ua kom nce siab rev-erb, sr9011 tuaj yeem inhibit qhov kev qhia ntawm cov noob lug ntawm BMALILY xws li BMAL1 thiab moos, yog tswj cov txheej txheem roj ntsha thiab metabolic.
Rog metabolism: hauv cov qauv nas, SR9011 tuaj yeem txo cov ntshav lipid, txo cov rog zuj zus, thiab nce hluav taws xob.
Cov metabolism: los ntawm kev tswj hwm cov noob muaj feem xyuam nrog Insulin zais ntshis (xws li GCK thiab SLC2A2), nws txhim kho cov kua dej zoo li.
Cov lus teb rau qhov tseeb: inhibits qhov kev qhia ntawm cov pro-inflammatory yam (xws li IL-6 thiab TNF-), txo cov lus teb rau kev tawm tsam.
SR9011 tuaj yeem inhibit qhov kev ua ntawm cov porcadian oscillator (xws li SCN Neurons) los ntawm Rev-Ref-Readay, uas ua rau:
Txo locomotor ua haujlwm hauv kev tsaus ntuj hauv cov nas.
Kev hloov pauv ntawm cov qib ntawm cov circadian cov caj ces (xws li Per2 thiab Crym).
Lub sijhawm rov qab ua tau zoo ib yam nrog cov tshuaj ntshiab sij hawm (<24 hours).
Cancer mis: SR9011 tuaj yeem ua rau G0 / G1 theem ntawm lub voj voog thiab tsis muaj kev cuam tshuam nrog ERT2.
Hepg2 hlwb: inhibits BMAL1 MRNA qhia nyob rau hauv rev-erb / -diompent yam.
Autophagy txoj kev kawm: txo cov naj npawb ntawm autophagosomes, ua rau P62 thiab Lysosome tsub zuj zuj.
Cov Qauv nas:
Ntse-nyob rau hauv cov noob qhia xws li Serpine1 (Fibrinolytic Plasninogen activor in entibitor 1 hom) thiab CYPESTEROL7 - hydroxylase).
Txo khiav kev coj tus cwj pwm log, nrog kev ua tau zoo (ed₅₀=56 mg / kg) sib xws ntawm rev-erb teb cov noob.
Qauv Nees Teb Qauv: tswj hwm lub scrcadian atherosclerosis ntawm autophagy noob.
Kev Nyab Xeeb thiab Kev Lom Zem
Cov Ntaub Ntawv Ceeb Toom
GHS07 Lo Lus ceeb toom: Lus ceeb toom (ua kom tawv nqaij, tawv nqaij thiab ua pa).
Cov lus phom sij:
H315: Ua rau daim tawv nqaij khaus.
H319: Ua rau lub qhov muag khaus heev.
Lus pom zoo
Hnav cov hnab looj tes tiv thaiv kev tiv thaiv, hnab looj tes thiab lub tsho loj.
Kev khiav lag luam hauv cov lus fume kom tsis txhob nqus plua plav ntawm cov plua plav lossis cov pa.
Khib nyiab yuav tsum tau ua raws li kev ntsuam xyuas kev nyab xeeb kev nyab xeeb.
Daim Ntawv Thov
Kev Tshawb Nrhiav Kev Tshawb Nrhiav
Kev tshawb fawb ntawm Circadian atherosclerosis.
Kev tshawb nrhiav ntawm cov txheej txheem ntawm cov kab mob metabolic (xws li rog, ntshav qab zib).
Kev tshawb fawb txog cancer cancer kev cai tswj thiab kev laus.
Muaj peev xwm saib xyuas tus nqi
Txawm hais tias nws tseem nyob hauv cov kev tshawb fawb preclinical theem, SR9011 qhia cov peev xwm hauv kev kho cov metabolic syndrome thiab mob kab mob.
Circadian atheroscler thiab pw tsis kho mob
Tub Ntxhais Mechanism
SR9011hmoov, raws li cov txhawb nqa / Euclear Receptor agonist, ncaj qha cuam tshuam hauv Mascillation Nucleus (SCN) los ntawm kev hais tawm ntawm cov khoom sib txuas ntawm BMAL1 thiab moos. Nyob rau hauv tus qauv nas, kev txhaj tshuaj tiv thaiv kev sib tw ua tiav (100 mg
Cov ntaub ntawv tshawb fawb ua ntej
Dav hlau lag syndrome qauv:Hauv cov dav hlau simulated kev sim, SR9011 tuaj yeem kho lub sijhawm pib dua ntawm lub circadian atherosclerosis thiab luv luv lub sijhawm xav tau kev yoog mus rau lub sijhawm tshiab ntawm 40%.
Pw tsaug zog theem hloov tsis meej:Rau fibroblasts muab tau los ntawm cov neeg mob uas tsis yog-24-teev pw tsaug zog, sr9011 tuaj yeem rov qab los ntawm cov Gra2 Gene, nrog cov amplitude nce ntawm 65%.
Hloov ua haujlwm simulation:Hauv kev ua haujlwm yuam ua haujlwm nas txuj ci, txuas ntxiv tswj hwm rau 7 hnub tuaj yeem txhim kho kev txawj ntse thiab txo qhov yuam kev ntawm 32%.
Cov Ntawv Thov Kev Kho Mob Muaj Peev Xwm
Lub hom phiaj kho ntawm pw tsaug zog theem ncua syndrome (DSPD)
Kev pab lub sijhawm thaj chaw cov tshuaj tiv thaiv ua rau muaj kev hla tebchaws
Kev cuam tshuam ntawm cov hluav taws xob nrawm sib cuam tshuam hauv cov neeg ua haujlwm ua haujlwm
Kev cuam tshuam rau cov metabolic syndrome
Rog meabolism kev cai
SR9011 HmoovUa kom lub Rev-ERB receptor thiab inhibits qhov qhia ntawm tus tseem ceeb enzyme srebp1c rau kev ua rog ntawm cov rog rhuav tshem noob lub noob pob. Hauv Dio (Kev pham-ua kev rog) nas qauv:
Cov thawj coj mus txuas ntxiv rau 28 hnub (100 mg / kg / hnub) tuaj yeem txo lub cev hnyav li 18%
Qhov nyhav ntawm cov kab mob rog uas muaj rog los ntawm 42%
Ntshav dawb fatty acid qib qis dua los ntawm 31%
Glucose audostasis txhim kho
Insulin rhiab: hauv 2-hom ntshav qab zib nas, sr9011 tuaj yeem rov qab ua kom lub siab insulin destrate-2 (irs-2), nce glucose cuam tshuam tus nqi los ntawm 2.3 zaug.
Cov piam thaj aabolism inabolism inhabolism inibition: los ntawm inhibiting qhov kev hais tawm ntawm qib pepck thiab g6pase, yoo ntshav cov roj teeb roj zoo txo los ntawm 28%.
Kev tiv thaiv ntawm tes: Hauv Min6 kab xov tooj, SR9011 Pretricement tuaj yeem txo cov tshuaj hauv xov tooj ntawm tes uas tsim los ntawm IL-1 los ntawm 57%.
Kev tswj hwm ntawm dyslipidemia
Txo cov lipoprotein tsawg (LDL) cov roj cholesterol los ntawm 35%
Nce siab lipoprotein (HDL) cholesterol los ntawm 22%
Txo Atherosclerotic Plaque Thaj Tsam los ntawm 41% (Apoe Knockout nas)
Pab Mob Cancer
Kev cai ntawm lub voj voog ntawm tes
Thaum muaj cancer ntawm tes (MCF-7, MDA-MB-231), SR9011 qhia tias:
Qhov kev faib ua feem ntawm G0 / G1 theem theem nce los ntawm 45%
Tus naj npawb ntawm cov xov tooj ntawm cov roj tsawg dua los ntawm 38%
Qhov kev qhia ntawm Cyclin D1 txo los ntawm 72%
Qhov kev qhia ntawm P21 nce ntxiv los ntawm 3.6 zaug
Inhibition ntawm autophagy flux
Hauv HEPG2 Mob Ntshav Cancer Hlwb, SR9011 kev kho mob ua rau 63% txo qis hauv tus naj npawb ntawm autophagosomes
Qhov piv ntawm LC3-II / LC3-Kuv txo qis los ntawm 51%
Kev txuam nrog ntawm P62 Protein nce los ntawm 2.8 zaug
Ua ke nrog kev kho mob txhim kho kev ua tau zoo
Thaum ua ke nrog Cisplatin, IC50 tus nqi ntawm zes qe menyuam kab mob cell (skov3) tuaj yeem raug txo los ntawm 8.2 μm
Thaum ua ke nrog paclitaxel, tus nqi kuaj mob ntawm lub cev nqaij hlav cancer mis tuaj yeem nce txij li 22% mus rau 58%
Hauv mob ntsws xenogrm duab qauv, thaum ua ke nrog PD-1 tshuaj tiv thaiv, lub qog ntim yog txo los ntawm 73%
Kev cuam tshuam rau cov kab mob neurodegenerative
Alzheimer tus qauv qauv
Nyob rau hauv 5xfad Transgenic mice, kev tswj hwm txuas ntxiv ntawm SR9011 rau 8 lub lis piam tuaj yeem:
Txo thaj chaw ntawm cov plaques los ntawm 39%
Rov kho cov synaptic ntom hauv cov hippocampus rau 82% ntawm theem tsiaj qus
Txhim kho kev ua tau zoo hauv Morris Dej Mazaze Kuaj, nrog kev khiav dim latency shortened los ntawm 47%
Parkinson tus kab mob tiv thaiv
Hauv MTP-induced nas cov qauv,SR9011hmoovTau:
Tiv thaiv dopaminininergic neurons nyob rau hauv lub txiaj ntsig nigra, nrog tus nqi muaj sia nyob nce ntawm 58%
Rov kho cov qib dopamine hauv cov striatum rau 71% ntawm cov hauv paus
Txhim kho kev ua haujlwm hauv kev ntsuas Rotarod, nrog 2.3 khawm ntxiv hauv lub sijhawm nyob
Inflammatory txoj kev cai tshuab
Inhibit kev ua kom zoo ntawm NLR3 inflammasome nyob rau hauv micoglia, nrog 64% txo qis hauv IL-1 zais cia
Txo cov kev qhia ntawm gfap hauv astrocytes los ntawm 39%
Txo qib theem ntawm tnf- hauv cerebrospinal kua los ntawm 52%
Txhim Kho Lub Cev Muaj Zog Kev Ua Haujlwm
Txhim kho ntawm kev ua siab ntev
Nyob rau hauv tus lej lej endionurance
Nce kev khiav deb ntawm 43%
Txhim khu cov pa oxygen uptake (vo2max) los ntawm 28%
Nce cov leeg mitochondrial ntom los ntawm 36%
Ceev cov leeg rov qab
Hauv cov leeg nqaij raug mob tsim los ntawm eccentric kev tawm dag zog, SR9011 tuaj yeem:
Txo Creatine Kinase (CK) TakePage los ntawm 47%
Ua kom nrawm qhov nqaij lub zog rov qab rau theem pib los ntawm 89%
Inhibit qhov kev qhia ntawm mob siab rau cov khoom siv tshuaj xyuas IL-6 los ntawm 62%
Txhim kho cov metabolic yooj
Txhawb nqa kev hloov pauv ntawm pob txha leeg los ntawm cov metabolism rau cov rog
Nce dua cov me me metabolic tus nqi los ntawm 19%
Nce kev faib ua feem ntawm cov roj ntshauv lub sijhawm ua kom qoj ib ce los ntawm 31%
Cim npe nrov: Sr9011 Hmoov, Tuam Tshoj Chaw Tsim Tshuaj, Chaw Tsim Tshuaj, Hoobkas, lag luam Wholesale, yuav, nqe, loj, loj, rau muag