/blog/WWL70/WWL70 anti-inflammatory therapeutics hana PGE2 da PGE2-G
Posted on 07 / 16 / 2018 by Dr. Patrick Young ya rubuta a WWL70. Yana da 0 Comment.
Dukkanin Mibolerone (Duba saukad da)
1.What ne WWL70?
2.Wene ne kayan WWL70?
3.WWL70 Bayani
4.How WWL70 yana aiki?
5.WWL70 Bayanin amfani
Hanyar 6.WWL70
7. WWL70 Sakamako
8.Wene ne sashin WWL70?
WWL70 bidiyo
I.WWL70 na ainihi Abubuwa:
Tsarin kwayoyin halitta: C27H23N3O3
Girman kwayoyin halitta: 437.5
Ajiye Temp: + 4 ° C
Color: Crystalline m
WWL70 yana da wani magungunan magani wanda zai iya hana aikin PGE2 da PGE2-G, da farko saboda ragewar COX-2 da kuma kwayoyin PGES-1 / 2 da ayyukan su na PGE2 a cikin kwayoyin microglia, da kuma a cikin Euse Mouse kwakwalwa.
WWL70 (CAS 947669-91-2) shi ne mai hanawa na musamman na 6 (ABHD6) na α-β-hydrolase, wani serine hydrolase wanda yake aiki a matsayin madadin hydrolase na endocannabinoid 2-arachidonoylglycerol (2-AG). Yana da darajar IC50 na 55-70 nM da 90-95% haramtawar ABDH6. An yi amfani da WWL70 a cikin nau'o'i daban-daban a matsayin abokiyar ABHD6.
An nuna shi don ceton kayan aikin mGluR5, wanda ya haifar da ciwo mai zafi a ratsan arthritic. An yi amfani da WWL70 don nuna cewa ABHD6 yana cikin aikin launin ruwan launin ruwan kasa da fararen launin launin fata, kuma yana da manufa mai mahimmanci game da kiba da kuma rubuta 2 ciwon sukari.
2.Wanne ne WWL70 abu?
Suna: WWL70
Formula kwayoyin: C27H23N3O3
Weight kwayoyin: 437.5
Tsarin Tsaji: + 4 ° C
α / β-Hydrolase domain 6 (ABHD6) yana daya daga cikin manyan enzymes don 2-arachidonoylglycerol endocannabinoid (2-AG) hydrolysis a cikin sel microglia. Ayyukanmu na baya-bayanan sun nuna cewa mai yin amfani da WWL6 mai hana ABHD70 yana da mummunar cutar da ƙananan ƙwayoyin cuta a cikin dabbobin dabba na traumatic kwakwalwa rauni da ƙananan sclerosis. Duk da haka, muhimmancin ABHD6 a cikin amsawar neuroinflammatory da kuma hanyoyin da WWL70 ke hana ƙin ƙonewa ba a riga an sama shi ba a cikin microglia mai amsawa.
Alal misali, Ayyukan hydrolytic da matakan 2-AG a cikin sel BV2 an auna su ta hanyar gwajin radioactivity da chromatography na ruwa wanda aka haɗa tare da alamomi na mashafi (LC-MS / MS). Maganar cyclooxygenase-2 (COX-2) da prostaglandin E2 (PGE2) sun haɗu a cikin microglia da aka yi tare da lipopolysaccharide (LPS) tare da / ba tare da WWL70 aka ƙaddara ta hanyar yammaci da kuma RT-PCR ba. An kirkiro 2-AG zuwa PGE2 ko PGE2-glyceryl ester (PGE2-G) ta immunoassay-linked linked enzyme (EIA) ko LC-MS / MS. An kirkiro hannuwan ABHD6 a aikin PGE2 ta yin amfani da magunguna da ƙananan ƙwayar RNA (siRNA).
Sakamakon WWL70 a kan aikin PGE2biosynthesis a cikin ƙananan ƙwayoyin ƙwayoyin cuta daga sassan BV2 da kuma kwakwalwa mai kwakwalwa na kwakwalwa (EAE).
Mun gano cewa WWL70 ya kaddamar da PGE2 a cikin ayyukan LCD na microgliavia cannabinoid masu zaman kansu, kodayake matakan kwayoyin 2-AG sun karu da WWL70 magani. Wannan raguwa ba'a iya fitowa ba a WWL70inhibition na ABHD6, saboda gaskiyar cewa bazuwar ABHD6 ta siRNA ko amfani da KT182, wani mai hana ABHD6 mai maye gurbin ya kasa yin amfani da PGE2.
WWL70 ta taƙaita maganganun COX-2 da PGES-1 / 2 da ke haifar da ƙaddamar da yanayin ƙwayoyin halitta na PGE2 da PGE2-G. Bugu da ƙari, an rage kayan aikin PGE2 daga arachidonic acid a cikin ƙananan ƙwayoyin ƙwayoyin cuta, yana nuna cewa WWL70also yana kai hari ga kwayoyin halitta na PGE2, wadanda za su iya taimakawa wajen hanyoyin maganin WWL70 a tsarin Euse Mouse.
WWL70 wani wakili ne mai maganin ƙurar jini wanda zai iya hana PGE2 da PGE2-G, da farko saboda ragewar COX-2 da kuma kwayoyin PGES-1 / 2 da ayyukan su na PGE2 na biosynthesis a cikin kwayoyin microglia, da kuma a EAE linzamin kwamfuta.
5.WWL70 Amfani bayanai
WWL70 ana ba da shi a matsayin mai ƙwayar murya. Za'a iya yin bayani na samfur ta hanyar narke WWL70 a cikin sauran kwayoyin da aka kwashe tare da iskar gas. WWL70 ne mai soluble a cikin kwayoyin halitta irin su DMSO da dimethyl formamide (DMF). Halin WWL70 a cikin waɗannan sunadarai kamar kimanin 1 mg / ml. WWL70 ne mai sauƙi mai narkewa a cikin buffers masu ruwa. Don matsakaicin iyakancewa a cikin buffers, WWL70 ya kamata a rushe shi a DMF sa'an nan kuma a diluted tare da buffer mai ƙyama. WWL70 yana da matsala na kusan 0.2 mg / mlin a 1: 3 bayani na DMF: PBS (pH 7.2) ta yin amfani da wannan hanya. Ba mu bayar da shawarar adana bayani mai mahimmanci fiye da ɗaya ba.
Ayyukan aikin hydrolytic da matakan 2-AG a cikin kwayoyin BV2 an auna su ta hanyar gwajin radioactivity da chromatography na ruwa wanda aka haɗa tare da alamomi na mashafi (LC-MS / MS). Maganar cyclooxygenase-2 (COX-2) da prostaglandin E2 (PGE2) sun haɗu a cikin microglia da aka yi tare da lipopolysaccharide (LPS) tare da / ba tare da WWL70 aka ƙaddara ta hanyar yammaci da kuma RT-PCR ba. An kirkiro 2-AG zuwa PGE2 ko PGE2-glyceryl ester (PGE2-G) ta immunoassay-linked linked enzyme (EIA) ko LC-MS / MS. An kirkiro hannuwan ABHD6 a aikin PGE2 ta yin amfani da magunguna da ƙananan ƙwayar RNA (siRNA). Hanyoyin WWL70 a kan aikin PY2 na biosynthesis a cikin ƙananan ƙwayoyin microsome daga cikin kwayoyin BV2 da kuma kwakwalwa na kwakwalwa na kwakwalwa (EAE).
7.WWL70 Sakamako
Mun gano cewa WWL70 ta kaddamar da aikin PGE2 a cikin microglia da aka kunna ta LPS ta hanyoyi masu zaman kansu na karɓa na iya ganewa, kodayake matakan kwayoyin 2-AG sun karu da WWL70 magani. Wannan raguwa ba a iya nunawa WWL70 ba na ABHD6, saboda gaskiyar cewa ABBD6 ta siRNA ko amfani da KT182, wani mai hana ABHD6 mai maye gurbin ya ɓace aikin PGE2. WWL70 ta taƙaita maganganun COX-2 da PGES-1 / 2 da ke haifar da ƙaddamar da yanayin ƙwayoyin halitta na PGE2 da PGE2-G. Bugu da ƙari, an rage yawan kayan PGE2 daga arachidonic acid a cikin sashin ƙananan ƙwayoyin cuta, yana nuna cewa WWL70 yana ƙaddamar da kwayoyin halitta na PGE2, wadanda za su iya taimakawa wajen hanyoyin maganin WWL70 a tsarin Euse Mouse.
8.Wace ne sashi na WWL70?
Solubility & Amfani da Bayanai:
DMSO zuwa 10 mM, bayyana (warmed)
Tabbatarwa da Solubility Shawara:
Wasu mafita na iya zama da wuya a sami kuma ana iya karfafawa
ta hanyar motsi, sonication ko m warming (a cikin 45-60 ° C
ruwa mai wanka).
Bayani game da zaman lafiyar kayayyaki, musamman a cikin bayani,
ya yi wuya an bayar da rahoto kuma a mafi yawan lokuta muna iya ba da kyauta
jagoran janar. Sha'idodin shawarwarinmu sune:
SOLIDS: An ba da ajiya kamar yadda aka bayyana akan lakabin samfurin kuma
Ana kulle alamar ta kulle, ana iya adana samfurin don har zuwa
6 watanni daga ranar da aka samu.
ABUBUWAN: Muna bada shawarar cewa mafita na jari, sau ɗaya
shirye, ana ajiye su a cikin takaddun da aka rufe a -20 ° C ko
a ƙasa da kuma amfani dashi a cikin watan 1. Duk inda za a samu mafita
ya kamata a yi shi kuma a yi amfani dashi a ranar.
α / β-Hydrolase domain 6 (ABHD6) yana daya daga cikin manyan enzymes don 2-arachidonoylglycerol endocannabinoid (2-AG) hydrolysis a cikin sel microglia. Ayyukanmu na baya-bayanan sun nuna cewa mai yin amfani da WWL6 mai hana ABHD70 yana da mummunar cutar da ƙananan ƙwayoyin cuta a cikin dabbobin dabba na traumatic kwakwalwa rauni da ƙananan sclerosis. Duk da haka, rawar da ABHD6 a neuroinflammatory martani da kuma sunadaren da wanda WWL70 cike kumburi ya ba tukuna aka daki-daki a cikin amsawa microglia.The hydrolytic aiki da matakan da 2-AG a BV2 Kwayoyin aka auna radioactivity kima da ruwa chromatography guda biyu tare da Harshen shafuka masu yawa (LC-MS / MS).
Maganar cyclooxygenase-2 (COX-2) da prostaglandin E2 (PGE2) sun haɗu a cikin microglia da aka yi tare da lipopolysaccharide (LPS) tare da / ba tare da WWL70 aka ƙaddara ta hanyar yammaci da kuma RT-PCR ba. An kirkiro 2-AG zuwa PGE2 ko PGE2-glyceryl ester (PGE2-G) ta immunoassay-linked linked enzyme (EIA) ko LC-MS / MS. An kirkiro hannuwan ABHD6 a aikin PGE2 ta yin amfani da magunguna da ƙananan ƙwayar RNA (siRNA). A sakamakon WWL70 a kan PGE2 biosynthesis aiki a cikin microsome sulusi da murabba'i daga BV2 Kwayoyin da gwaji autoimmune encephalopathy (EAE) linzamin kwamfuta kwakwalwa da aka ma examined.We gano cewa WWL70 suppressed PGE2 samarwa a LPS-kunna microglia via cannabinoid tsoka mai amsa sigina-m sunadaran, ko da yake kwayuka matakan na 2-AG an ɗaukaka shi ta hanyar WWL70 magani.
Wannan raguwa ba a iya nunawa WWL70 ba na ABHD6, saboda gaskiyar cewa ABBD6 ta siRNA ko amfani da KT182, wani mai hana ABHD6 mai maye gurbin ya ɓace aikin PGE2. WWL70 ta taƙaita maganganun COX-2 da PGES-1 / 2 da ke haifar da ƙaddamar da yanayin ƙwayoyin halitta na PGE2 da PGE2-G. Bugu da ƙari, PGE2 samarwa daga arachidonic acid da aka rage a cikin microsome sulusi da murabba'i, ya nuna cewa WWL70 ma hari PGE2 biosynthetic enzymes, wanda na iya taimakawa wajen warkewa sunadaran da WWL70 a EAE linzamin kwamfuta model.WWL70 ne wani anti-kumburi warkewa wakili iya inhibiting PGE2 da PGE2-G samar, da farko saboda ta rage Cox-2 da microsomal PGES-1 / 2 magana da su PGE2 biosynthesis aiki a microglia Kwayoyin, kazalika a EAE linzamin kwamfuta kwakwalwa.
Ayyuka na ayyuka na WWL70 a kan PGE 2 da PGE 2 -G samarwa a microglia. 2-AG ne yafi dacewa da acid arachidonic, wanda ya juya zuwa PGE 2 ta hanyar catalysis na COX-1 / 2 da mPGESs. WWL70 damuarn ABHD6 game da shi kara da matakan 2-AG da kuma rage samar da PGE 2 da inhibiting PGE 2 roba enzymes. 2-AG kuma za a iya oxygenated da Cox-2 sa'an nan tuba zuwa PGE 2 glycerol ester da mPGESs, wanda aka kuma hana ta WWL70
Tags: saya WWL70 foda, WWL70 foda
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