Yonke into ngeMibolerone (Hlola amaconsi)

I-1.JZL-184 Iingxelo
I-2.Biochem / physiol Actions-CAS: 1101854-58-3
I-3.JZL-184 Isiseko seSistim kwi-Weight
I-4.JZL-184 Impembelelo kwiNuroprotective
5. I-JZL-184 Iphucula indlela yokuziphatha kunye neempahla ze-Neural
6.Buy JZL-184 kwi-JZL-184 Abaxhasi abathembekileyo kwi-intanethi


Ividiyo yeJZL 184


I.JZL 184 Abalinganiswa basisiseko:

igama: JZL 184
CAS: 1101854-58-3
I-molecular Formula: C27H24N2O9
Isisindo somzimba: 520.48746
Melt Point:
Isitoreji sokugcina: -20 ° C
umbala: Uluhlaza obomvu


1. Iingxelo ze-JZL-184aasraw

I-JZL-184 (1101854-58-3) i-inhibitor enamandla kwaye ekhethiweyo ye-MAGL kunye ne-IC50 ye-8 nM kunye ne-4 μM ukwenzela ukuvinjelwa kwe-MAGL ne-FAAH kwimimbrane yobuchopho. Ixabiso le-IC50: I-8 nM I-Target: i-MAGL inhibitor kwi-vitro: I-JZL-184 ilandisa i-DSE kwi-Purkinje neurons kwiimpawu ze-cerebellar kunye ne-DSI kwi-CA1 i-pyramidal neurons kwimigqomo ye-hippocampal. I-JZL-184 inamandla kakhulu ekuvimbeleni i-mouse MAGL kune-rat MAGL. kwi-vivo: Xa ilawulwa kwiigundane kwi-16 mg / kg, i-intraperitoneally, i-JZL-184 iyanciphisa umsebenzi we-MAGL ngu-85%, iphakamisa amaqondo e-2-AG ngengqondo nge-8, kwaye yenza umsebenzi ohlotshaniswayo kwiimvavanyo zeentlungu ezinokulinganisa ophakathi kwe-cannabinoid (CB1). Ukulawulwa kakuhle kwe-JZL-184 ku-FAAH (- / -) iigundane zithuthukise ubukhulu be-subset yeempendulo ezingenanto, eziphindaphindiweyo I-JZL-184 unyango kwakhokelela kwaphela imiphumo antinociceptive, umnqamlezo nokunganyamezelwa neziphumo amayeza ka Δ-tetrahydrocannabinol, izinciphiso CB1 receptor agonist-kwavusa guanosine 5'-O- (3 - [(35) S] thio) triphosphate siyabophelela, kunye nokuxhomekeka njengoko kuboniswe ziimpawu zokuzihoxisa, ezingakhathaliseki i-genotype.

I-Endocannabinoids efana ne-2-arachidonoyl glycerol (i-2-AG) kunye ne-arachidonoyl ethanolamide (AEA) i-lipids esebenzayo yezinto eziphilayo ezibandakanyeka kwinkqubo ye-synaptic equka ukusebenziselwa kwamkeleki e-cannabinoid. I-Monoacylglycerol lipase (MAGL) yi-serine hydrolase ejongene ne-hydrolysis ye-2-AG i-arachidonic acid kunye ne-glycerol, ngaloo ndlela iphelisa umsebenzi wayo. JZL-184 yi inhibitor esinamandla yaye uyakhetha of monoacylglycerol lipase (MAGL) olubonisa IC50 amaxabiso 8 NM kunye 4 μM ukuze inhibition of MAGL uyadinga acid amide hydrolase kwi imifinya ingqondo mouse, respectively.1 Xa elawulwa ukuba iimpuku kule 16 mg / kg, intraperitoneally, JZL-184 kunciphisa umsebenzi MAGL nge 85%, liziphakamisa ingqondo amanqanaba 2-AG ngu 8-emhlambini, livuselela umsebenzi iintlungu kwiimeko ezahlukeneyo zePCR ntlungu ngokomgangatho ufana nqwa ngqo central cannabinoid (CB1) agonists.

I-JZL -184 Abalingani abaSebenzi

Igama elongezelelweyo JZL-184
formula formula
MW 520.5
imvelaphi AASraw
CAS 1101854-58-3
Ukungcola ≥98% (TLC)
Kubonakala Uluhlaza obomvu
Umzimba I-Soluble kwi-DMSO (10mg / ml)


2. Izenzo ze-Biochem / physiol-CAS: 1101854-58-3aasraw

I-JZL-184 inqanda i-MAGL, i-enzyme eyona nto ijongene nokuthotywa kwe-endocannabinoid 2-arachidonoylglycerol (2-AG). I-Anandamide kunye ne-2-AG ziyi-endocannabinoids ezinokuphela ezinokuthi zenze i-receptors ye-cannabinoid CB1 ne-CB2. I-Anandamide ixhaswa kakhulu ngamafutha ase-acide hydrolase (FAAH), kanti i-monoacylglycerol lipase (i-MAGL) icingelwa ukuba yi-enzyme eyona nto ibangela uxanduva lwe-2-AG. Kunzima ukwahlula imisebenzi yezo zibini kuba ezininzi ezikhoyo ezikhoyo kwi-MAGL azikhethi, kwaye zivimbela i-FAAH okanye ezinye i-enzymes. I-JZL-184 iyona yeyokuqala inhibitor yokukhetha ye-MAGL kunye ne-nanomolar portency kunye no-200-fold selectivity for MAGL vs FAAH. Xa ilawulwa kwiigundane, i-JZL-184 yanda amazinga e-2-arachidonoylglycerol ebuchosheni malunga ne-8, ngokungekho miphumo kumanqanaba e-anamamide.

I-JZL184 (i-1101854-58-3) i-inhibitor eqinile nekhethiweyo ye-Monoglyceride Lipase (i-monoacylglycerol lipase, i-MAGL).


3. JZIsiseko se-L-184 kwisisindoaasraw

Ukuthelekisa imiphumo yokulawulwa ngokuphindaphindiweyo kwezinga eliphantsi ukuya kumazinga aphezulu e-JZL-184 emsebenzini we-CB1 kwi-brain, iigundane zifakwe ngee-doses ezihlukeneyo kwi-25-fold range okanye imoto yeentsuku ze-5 ezilandelanayo. I-protocol ye-G-protein ye-CB1 esebenzayo i-activation yahlolwa ngokusetyenziswa kwee-curves-effect curves ze-GXXXS ekhutshwe yi-CP55,940 ebopha kwiimbrane ezilungiselelwe kwi-homogenate yamagundane. Njengoko kuboniswe kumzobo we-1A, i-dosing ye-16 kunye ne-40 mg / kg ye-JZL184 ekhutshwe, ngokulandelanayo, i-46 kunye ne-56% yokunciphisa kwi-CP-NXX-protein ye-G-protein eyenziweyo (i-Emax), engenasiphumo I-JZL-184 dose kwiiC55,940 EC50. Ngokwahlukileyo, amanani e-JZL184 aphantsi (i-1.6, i-4, okanye i-8 mg / kg) ayizange ifuthe i-CP55,940 Emax okanye i-EC50. Ukufumanisa ukuba iziphumo zeJZL-184 ekusebenziseni kwe-G-protein ye-CB1 ye-receptor edibeneyo idibene ne-CB1 ye-receptor level, uhlalutyo olubophezelayo lwe-CB1-SR141716A lwaluqhutyelwa kwiinkonzo ezilawulwa ngokuphindaphindiweyo i-JZL-184 (1.6, 4, 16 , okanye i-40 mg / kg) okanye isithuthi, njengoko kuchaziwe ngaphambili. Ukuphindaphinda kwakhona nge-16 kunye ne-40 mg / kg i-JZL184 inciphise ixabiso le-R141716A Bmax nge-30 kunye ne-35%, ngokulandelanayo. Nangona kunjalo, ukulawulwa ngokuphindaphindiweyo kwamanani aphantsi ka-JZL-184 akuzange iguqule ngokuphawulekayo ixabiso le-SR141716A Bmax. I-BasalGTPyS yokubopha ayizange ithinteke ngonyango oluphindaphindiweyo kunye naliphi na umthamo we-JZL-184. Ngaphezu koko, ixabiso le-SR141716A KD alizange lichaphazeleke ngonyango oluphindaphindiweyo kunye nawaphi na amayeza e-JZL-184 ahlolwayo.


4. JZL-184 Iziphumo kwiNeuroprotectiveaasraw

Ubungqina obukhulayo bubonisa ukuba inkqubo yokugcina i-endocannabinoid idlala indima ekukhuseleni i-neuroprotection kwisifo sika-Parkinson. Kungekudala, sibonise neuroprotective effect ye-monoacylglycerol lipase (MAGL) inhibition ngeJZL-184 kwi-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) imodeli ye mouse. Nangona kunjalo, uphando olongezelelweyo lufunekayo ukuchonga iindlela ze-neuroprotective ze-endocannabinoid kwinkqubo ye-nigrostriatal. Injongo yalo msebenzi kukuphanda ukuba i-neuroprotective effect ye-JZL-184 kwimigundane inganwezelwa kwi-in vitro model cell ukuze iqhube ukuqonda indlela yokwenza isilwanyana. Umgca we-SH-SY5Y ukhethwe ngokusekelwe kwi-phenotype yayo efana ne-dopaminergic kunye ne-1-methyl-4-phenylpyridinium iodide (MPP +) yetyhefu. Ngaphezulu, i-SH-SY5Y iiseli zivakalisa zombini i-receptors ye-cannabinoid, i-CB1 ne-CB2. Uphononongo lwangoku lubonisa umphumo we-neuroprotective of MAGL inhibition kunye ne-JZL-184 kwi-SH-SY5Y iiseli eziphathwe nge-MPP +. Iimpembelelo ze-JZL-184 kwi-cell survival ivaliwe yi-AM630, i-CB2 i-receptor antagonist, kwaye yafaniswa neJWH133, i-CB2 receptor agonist. I-Rimonabant, i-CB1 i-receptor antagonist, ayizange ifuthe i-JZL-184-induced cell survival. Ezi ziphumo zibonisa ukuba i-neuroprotective effect ye-MAGL inhibition kunye ne-JZL-184 echazwe kwizilwanyana zesifo se-Parkinson ingahanjiswa kwiimodeli ze-vitro ezifana ne-SH-SY5Y iiseli eziphathwe nge-MPP +. Oku kubonisa ithuluzi eluncedo lokufunda iindlela zokukhusela i-neuroprotection egxininiswe yi-MAGL inhibition, kwaye sibonelela ngokubandakanyeka kokubandakanyeka kwe-CB2 receptors ekuphuculeni ukusinda kweseli.

I-JZL184 (i-1101854-58-3) i-inhibitor eqinile nekhethiweyo ye-Monoglyceride Lipase (i-monoacylglycerol lipase, i-MAGL).


5. JZL-I-184 Iphucula indlela yokuziphatha kunye ne-Neural Properties-umzekelo we-Down Syndromeaasraw

(1) Abstract kwi-Inhibitor JZL-184(1101854-58-3)

Ukuguqulwa kwe-Genetic okanye unyango lwe-pharmacological oluchaphazela ukubonakaliswa kwe-endocannabinoid lunempembelelo enzulu kwiimpawu ze-synaptic kunye ne-neuronal kwaye, phantsi kweemeko ezithile, kunokuphucula imisebenzi ephezulu yengqondo. I-Down syndrome (i-DS), ingxaki yokuphuhliswa ebangelwa ukuphindaphinda kwe-chromosome 21, ibonakaliswe ngokungaziqondi kakuhle nokuphuhliswa okungenakukhuselwa kwesifo se-Alzheimer (AD). Apha wasebenzisa JZL-184, inhibitor akhetha monoacylglycerol lipase (MAGL), ukuba ukuhlola indlela bezifo MAGL inhibition kwiipropati zokuziphatha, kwemichiza, kwaye zobuchopho yeempuku owalupheleyo Ts65Dn, umfuziselo yemfuza of DS. Kwimizimbini ye-ts65Dn kunye ne-normosomic (2N) yokulawula, unyango lwe-JZL-184 lonyuka amanqanaba eengqondo ze-2-arachidonoylglycerol (2-AG) kunye nokunciphisa amanqanaba e-metabolites njenge-arachidonic acid, i-prostaglandins i-PGD2, i-PGE2, i-PGFa kunye ne-PGJ2. Ukuphuculwa komsebenzi wokwenza umsebenzi we-Ts65Dn kancinci kuncitshiswe ngonyango lwe-JZL-184 kumanqanaba athathwa kwizilwanyana ze-2N. Imemori engapheliyo yexesha elide nayo yaphuculwa, ngelixa iifutshane zexesha kunye neentsuku zokusebenza zeememori zazingekho. Ukongezelela, ukunciphisa i-hippocampal yexesha elide inokwenzeka (LTP) yanyuswa kwi-JXL-184 ephathwe i-Ts65Dn iigundane kumanqanaba athathwa kwiigundane ze-2N. Okuthakazelisayo, utshintsho kwiplastiki kunye neendlela zokuziphatha azizange zibonwe kwiigundane ze-184N eziphathwe nge-JZL-2 ezibonisa ukuba unyango lujolise ngokukodwa ukusilela kwizilwanyana ze-trisom. Ukwelashwa kwe-JZL-184 kwanciphise amanqanaba ka-Aβ40 kunye ne-Aβ42, kodwa ayizange ibe nempembelelo kumanqanaba opheleleyo we-APP kunye ne-BACE1 kumabini ama-ts65Dn kunye ne-2N iigundane. Ezi nkcukacha zibonisa ukuba ukuguqulwa kwe-MAGL engapheliyo kuphucula ukuziphatha kunye nemisebenzi yengqondo kwi-DS imodeli ebonisa ukuba ukujoliswa kwe-pharmacy ye-MAGL ingathathwa njengendlela entsha yokuphucula ukuqonda kwi-DS.

(2) Ingxoxo kwiJZL-184 Imiphumo

I-JZL-184 Impact, Inhibitor JZL-184

Ukuguqulwa kwe-Genetic okanye unyango lwe-pharmacological oluchaphazela amaqondo okuphela kwengqondo ye-endocannabinoids lunempembelelo enkulu kwiimpawu ze-synaptic kunye ne-neuronal kwaye, phantsi kweemeko ezithile ezithile, kunokuphucula imisebenzi ephezulu yengqondo. I-endocannabinoid eyona nto ininzi kwi-brain is 2-arachidonoylglycerol (2-AG). Efana nezinye iamolekyu ze-lipid zokubonisa, amanqanaba e-2-AG alawulwa ngokulinganisela kwe-biosynthesis kunye nokuhlaziywa. I-enzyme yenqununu ye-hydrolytic ejongene nokuthotywa kwe-2-AG i-monoacylglycerol lipase (MAGL). Ngenxa yoko, i-genetic okanye ukunyuswa kwe-pharmacological ye-MAGL isiphumo sokwenza ukwanda okukhulu kweengqondo ze-2-AG kunye nokunciphisa kokunciphisa i-arachidonic acid kunye ne-eicosanoid metabolites. Ngaloo ndlela, ukuvinjelwa kwe-MAGL kunokunyusa amanqanaba e-2-AG, okwenza ukuba kusebenze i-receptor ye-cannabinoid, kunye nokunciphisa ukukhululwa kwe-eososanoids, okubangelwa ukuxothwa kwe-pro-inflammatory sign in system system. Kungekudala, kuboniswe ukuba ukuvinjelwa kwe-MAGL kunye ne-JZL-184, i-MAGL inhibitor ekhethekileyo kunye neyobuchule, iplastiki ye-synaptic ephuculweyo kunye nenkumbulo kwimifanekiso yemouse ye-Alzheimer's disease (AD). Ukongezelela, i-MAGL KO amagundane nayo yabonisa ukwanda kwe-synaptic plasticity kunye nememori, ebonisa ukuba ukuphazanyiswa komsebenzi we-MAGL kungabangela ukuba kuthinteke umsebenzi ophezulu wengqondo. Ekugqibeleni, ukuveliswa kwemvelo okanye i-pharmacological inactivation ye-MAGL ukukhutshwa ngokugqithisileyo kwe-β-amyloid (Aβ) kwimodeli ye-AD.
I-Down syndrome (i-DS) yinkinga yokuphuhliswa ebangelwa ukuphindaphinda kwe-chromosome 21. Iimodeli zofuzo ze-DS zithatha ikopi eyongezelelweyo yeejethi ezixhomekeke kwii-chromosome zabantu ze-21. Enye yezinto ezisetyenzisiweyo ezisetyenzisiweyo ze-DS, i-trisomic Ts65Dn iigundane, zineekhophi ezintathu zeentsholongwane kwi mouse Chr 16 eziyi-homologues zengqungquthela ze-Chr 21, kuquka ne-App gene. I-ts65Izinkoma zibonisa ukungaqhelekanga kwisakhiwo sengqondo, ukuqonda, kunye nokuziphatha okufana nezo zibonwa kubantu abane-DS. Ngaloo ndlela, bobabini abane-DS kunye ne-Ts65Dn iigundane abanalo imemori exhomekeke kwi-hippocampus, imemori yokusebenza, ibonisa i-dendritic ezininzi, i-synaptic, ne-neuronal engafanelekiyo, kwaye ibonisa uhlobo lwe-AD olulandelayo lokuphila.
Apha sihlolisise Imiphumo ye-JZL-184 kwiipropati ze-neural kunye nokuziphatha kwama-ts65Dn. Siye sabona ukuba ukukhutshwa okungapheliyo kwe-MAGL kwandiswe amanqanaba eengqondo ze-2-AG, umsebenzi obuye wenziwa ngokuzenzekelayo, kunye nokukhunjulwa kwexesha elide kunye neeplastiki zeplastiki kwi-k65Dn. Ukongeza, i-JZL184-unyango linciphile amanqanaba e-Aβ40 kunye ne-Aβ42 kokubili i-Ts65Dn kunye ne-2N amagundane. Ezi ziphumo zikhomba kwi-MAGL njenge-novel ekujoliswe kuyo ekujoliseni ukuphucula ukuqonda kunye, mhlawumbi, ukuphucula i-AD-type neuropathology ngexesha lokuguga kubantu abane-DS.

(3) Isiphetho-Inhibitor JZL-184

Siyabona apha ukuba ukuvinjelwa okungapheliyo kwe-MAGL kunye ne-inhibitor ekhethiweyo i-JZL-184 yenzelwe umsebenzi wokwenza umsebenzi kunye nokuphucula imemori yesikhathi eside kunye neeplastiki zeplastiki kwi-Ts65Dn iigundane, umzekelo we-DS. Ukwelashwa kwe-JZL-184 kwakungekho mpe mbelelo kwizinto zokuziphatha kunye neplastiki ye-plastiki ye-normosomic lawula amagundane ebonisa ukuba ukukhutshwa komsebenzi we-MAGL kusebenza ngokukodwa kwi-DS. Olu unyango lwanciphisa amanqanaba e-Aβ40 kunye ne-Aβ42 kodwa ayinaso impembelelo kumanqanaba apheleleyo ubude be-App kunye ne-BACE1 kumabini ama-ts65Dn kunye ne-2N. Ngokubambisana, ezi ziphumo zibonisa ukuba ukujoliswa kwe-pharmacy ye-MAGL kungabonisa inveli kunye nendlela ethile yokwelapha ekuphuculeni ukukhubazeka kwengqondo kwi-DS.


6. Thenga i-JZL-184 kwi-JZL-184 Suppliers onlineaasraw

(1) I-JZL-184 abathengi kwi-intanethi-AASraw

Ngokutsho kophando lwemarike, abaninzi abathengi be-JZL-184 abakwazi ukubonelela nge powder JZL-184, ingakumbi i-JZL-184 powder. Njengokuba siyazi, i-China ne-India zibonelela ngeenkonzo ezinkulu zokuvelisa iyeza. Ixabiso le-powder yase-Indiya lixabiso elincinci, kwaye umgangatho we powder ukwabonakala kwakhona.Ixabiso le-powder e-China lihluka kakhulu, kodwa konke kuxhomekeke kumgangatho weemveliso. Ngokukodwa, namhlanje, urhulumente waseTshayina olawula ngokuthe ngqo ukuveliswa kwe powder kunye nokuhlolwa kwayo ngokungqongileyo kwokhuselo lokusingqongileyo kuye kwabangela ukudideka okukhulu kwintengo yemakethe ye powder. I Ixabiso le-JZL-184 Kuye kwahluke. Nantsi, ndincoma umenzi we-JZL-184-AASraw.
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(2) Isikhokelo sokuthenga JZL-184 Inyathelo nenyathelo

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Thenga i-JZL-184, abaxhasi be-JZL-184, ixabiso le-JZL-184, umenzi we-JZL-184


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