I-ARA-290 yi-peptide yokwenziwa eyenziwe 11 iiamino acids, ephuma kwimodeli yolwakhiwo olunemigangatho emithathu yehomoni engapheliyo erythropoietin (EPO). Ilinganisa i-interface ebophelelayo ye-erythropoietin receptor β-co-receptor (βcR), ngokukhetha isebenze iprotheni ye-receptor yokulungisa. Okubaluleke ngakumbi, le ndlela yokuthintela ubungozi obunokunxulunyaniswa nezamkeli ze-EPO zemveli.
Kuqale kwaxelwa kwi 2008, ukuvela kwe-ARA-290 kubonisa utshintsho olucwangcisiweyo kuphando lwe-EPO ukusuka kunyango lwe-hematopoietic ukuya ekulungisweni kwezicubu ekujoliswe kuzo kunye. immunomodulation.
Ngoomatshini, ngokuzibophelela ngobudlelwane obuphezulu kwi-IRR, I-ARA-290 ngokukhethayo yenza ukuba kusebenze iindlela ezingundoqo zokubonisa umlambo, kuquka I-JAK2-STAT3 kwaye PI3K-Act, leyo ekugqibeleni imodareyitha iimpembelelo ezibalulekileyo ezifana NF-kB.
Ngaphaya koku, I-ARA-290 ibonisa imiphumo enamandla yokuchasana nokuvuvukala kunye ne-immunomodulatory, ikhuthaza ukulungiswa kwe-neural kunye nokunciphisa intlungu ye-neuropathic, ilawula imetabolism, kwaye ibonisa amandla onyango okunyanga i-fiber neuropathy encinci, Isifo sikaCharcot-Marie-Tooth, kunye ne-diabetes neuropathy.
Ulandelelwano
H-Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser-OH
Inombolo yeCAS
1208243-50-8
Ifomula yeemolekyuli
I-C51H84N16O21
Ubunzima beMolekyuli
1257.3
Uphando lwe-ARA-290
1.Ukuphucula iAngiogenic Potential kunye neHoming Capacity ye Iiseli ze-Endothelial Progenitor ezijikelezayo:
- Okokuqala, izifo ze-ischemic zibonakalisa ukuphazamiseka kwemithambo yegazi. Ngokuxhaphaka kokutyeba kunye nesifo seswekile, inani lezigulane ezichaphazelekayo liyaqhubeka nokunyuka. Ngenxa yoko, kubantu abanesifo esinzima se-vascular, ukunqunyulwa amalungu kuhlala kulukhetho lokuqala lonyango.
- Kuphononongo olufanelekileyo, I-ARA-290 inikwe iimpuku nge i-ischemia yelungu elingapheliyo (CLI). Iziphumo zibonise ukuba i-ARA-290 yonyusa kakhulu ukwanda / ukufuduka kunye nokuchasana ne-apoptosis eyenziwe nge-hydrogen peroxide..
- Ukongeza, inaliti enye ye-ARA-290 iphucule ukuhamba kwegazi kwelungu kunye noxinzelelo lwe-capillary.
Ngokudibeneyo, ezi ziphumo zibonisa ukuba ukusebenzisa i-ARA-290 njenge-adjuvant kunokuphucula iimpawu ze-angiogenic zangaphakathi. I-Endothelial colony yenza iseli(IiECFCs) kunye ne-vivo yabo ukuya kwiindawo ze-ischemic, ngaloo ndlela ivuselela i-angiogenesis. Ngaloo ndlela, oku kubonelela ngendlela entsha yonyango yezifo ezingapheliyo ze-ischemic.
2.Ukuphucula ukukhutshwa kwe-insulin kunye nokuNyamezelwa kweGlucose kuHlobo 2 Izigulana zesifo seswekile:
Kwi-domain ye-metabolic, I-ARA-290 iphucula kakhulu ukunyamezela kweglucose kwiimpuku zesifo seswekile ngaphandle kokuchaphazela iigundane ezingenasifo seswekile.. Ngokuthe ngqo, ivuselela ukuphakama GSIS(I-Glucose-Stimulated Insulin Secretion) amanqanaba, ekugqibeleni kuphuculwe i-glucose oxidation kunye Adenosine triphosphate(ATP) imveliso. Ngale ndlela, ngempembelelo I-ATP-sensitive potassium channel(CAT) ukuvalwa komjelo, ekugqibeleni ichaphazela ukukhutshwa kwe-insulin.
3.I-Anti-inflammatory kunye ne-Neuroprotective Effects:
Ukuvavanya i-neuroinflammation, kulingo lonyango olubandakanya iimpuku zika Lewis nge uvavanyo lwe-autoimmune encephalomyelitis (EAE), ulawulo oluqhubekayo lwe-ARA-290 i-injection yanciphisa kakhulu ubunzima be-EAE kwiigundane. Ukuthi ngqo, olu nyango lunciphisa ukuqokelelwa kweeseli ezivuthayo kwintambo yomgogodla ye-EAE kwaye yacinezela ukwanda kunye nokubonakaliswa kwee-cytokines ezifana ne-interleukin., ithumba necrosis factor-α, kunye ne-inducible i-nitric oxide synthase kwi-EAE ibuzi intambo yomgogodla.
Ngaphaya koko, izifundo ze-in vitro zibonise ukuba i-ARA-290 iyanqanda Th1 kunye Th7 iseli i-polarization kwi-EAE lymphocytes. Kunye, olu lingelo lubonisa ukuba i-ARA-290 inexabiso lonyango elinokubakho kwi-multiple sclerosis.
4.Ukukhuthaza ukulungiswa kweNeural kunye nokunciphisa iintlungu zeNeuropathic:
Ngokucacileyo, I-ARA-290 inokuwela ngokuthe ngqo umqobo wegazi-ubuchopho, ukuyivumela ukuba isebenze ngokuthe ngqo Umqolo weengcambu ze ganglia kwaye microglia. Pha, icinezela ukukhutshwa okungaqhelekanga kwinkqubo yengqondo ephakathi, kunciphisa uvakalelo oluphakathi, kwaye imodareyitha ngenkuthalo izinto ze-neurotrophic ngelixa inciphisa ukudumba kwi-dorsal root ganglia ukulungisa inkqubo ye-nervous central..
5.Ukuphucula ukulungiswa kweTissue kunye neSakhono sokuHlaziya:
Ekugqibeleni, I-ARA-290 isebenza kwiiseli zokhuselo lomzimba ezibonisa i-IRR, ekhuthaza ngamandla i-polarization yabo kwi-pro-inflammatory M1 phenotype ukuya kwi-anti-inflammatory kunye ne-pro-repair M2 phenotype. Nje ngeziphumo, icinezela iimpendulo ezivuthayo ezigqithisileyo ngelixa ivuselela ukukhuselwa kwezinto ezininzi zokukhula, ukucoca iiseli ze-apoptotic, kunye nokwenza imithambo yegazi emitsha. Ekugqibeleni, oku kuphucula ukunyaniseka kwesakhiwo kunye neempawu zemishini yezicubu ezilungisiweyo.
I-COA
HPLC
NKSK
