ARA-290 16mg

▎ ya ARA-290 Imiterere

Inkomoko: PubChem

Urukurikirane: XEQLERALNSS Inzira ya molekulari: C 51H 84N 16O.21 Uburemere bwa molekuline: 1257.3g / mol CAS Umubare ： 1208243-50-8 PubChem CID ： 91810664 Synonyme: Cibinetide

▎ ARA-290 Ubushakashatsi

Ni ubuhe bushakashatsi bwakozwe muri ARA-290?  

Iterambere rya ARA-290 ryaturutse ku gucukumbura ubushobozi bwo kuvura erythropoietin (EPO). Abahanga basanze EPO idatera erythropoiesis gusa ahubwo ifite n'imikorere irinda ingirangingo nka anti-inflammation na anti-apoptose. Nyamara, gutera imbaraga kwa EPO hematopoietic bishobora kongera ubwonko bwamaraso nizindi ngaruka, bikagabanya imikoreshereze yabwo mu kuvura indwara zitari nke. Kugirango bagumane ingaruka zo gukingira ingirabuzimafatizo za EPO mu gihe birinda ingaruka mbi za hematopoietic, abashakashatsi batangiye gukora peptide ikomoka, bituma habaho ARA-290.  

Hamwe n'ubushakashatsi bwimbitse, ibyiza byihariye bya ARA-290 nka peptide itari hematopoietic peptide byamenyekanye buhoro buhoro. Ikora anti-inflammatory na tissue gusana inzira yerekana inzira ihuza reseptor yo gusana ivuka (IRR), ikerekana ingaruka zitanga ikizere mukuvura ibibazo bya diyabete, neuropathies, n ibikomere byimpyiko. Ibyavuye mu bushakashatsi byashizeho urufatiro rw’ubushakashatsi n’ubuvuzi bwa ARA-290 kandi biteza imbere ingamba zo kuvura udushya dushingiye kuri peptide ikomoka kuri EPO.  

Ni ubuhe buryo bwo gukora bwa ARA-290?  

Ingaruka zo Kurwanya Indwara: ARA-290 ibuza gusohora cytokine ikongora, bityo bikagabanya ibisubizo byumuriro, nkuko bigaragara mubyitegererezo byinshi byindwara. Kurugero, muburyo bwimbeba ya sisitemu ya lupus erythematosus (SLE), igabanya ubukana bwa serumu ya cytokine ikongora IL-6, MCP-1, na TNF-α, igatera ibimenyetso bya SLE {#Dahan, A, 2016} (Dahan A, 2016). Muri moderi ya cisplatine iterwa na nephrotoxicity, igabanya cytokine itera TNFα, IL6, na IL1β, igabanya uburibwe bwimpyiko ^[2] (Ghassemi-Barghi N, 2023). Uburyo bwayo bwo kurwanya inflammatory bushobora kuba bukubiyemo kwibasira imiti ivuka (IRR), heterodimer ya erythropoietin reseptor na β-rusange (CD131). Guhambira kuri IRR ikora inzira yo kurwanya anti-inflammatory inzira yerekana inzira, bityo bikagabanya gucana ^[1].

Ingaruka zo kurwanya Apoptotique: ARA-290 ibuza apoptose selile kandi igatera ingirabuzimafatizo kubaho. Muburyo bwimbeba ya diyabete, irwanya impyiko epithelial selile apoptose kandi igabanya imvugo ya protease zingenzi mubikorwa bya apoptotique, bityo bikagira ingaruka zo gukingira impyiko. Muri moderi ya cisplatine iterwa na nephrotoxicity, igenga imvugo ya poroteyine zijyanye na apoptose nka Bax na Bcl-2, ikabuza ibikorwa bya Caspase-3, igabanya apoptose selile, kandi ikagabanya kwangirika kwingirangingo ziterwa na cisplatine ^..  

Ingaruka zo kurwanya Oxidative: ARA-290 ibuza kwangirika kwa okiside kandi igabanya umusaruro w’ibintu byangiza nkubwoko bwa ogisijeni ikora (ROS). Mu bwoko bw'impyiko ya diyabete, irwanya imiterere y'impyiko, igabanya urugero rwa ROS, kandi igabanya imvugo ya malondialdehyde (MDA), igabanya impyiko ziterwa na okiside iterwa no kwangirika kw'impyiko. Mu bushakashatsi bwa aterosklerose, mu bushakashatsi bwa vitro bwerekana ko ARA-290 ibuza umusaruro wa ROS muri macrophage mu bihe by’umuriro, bikagabanya kwangirika kwa okiside kwangiza selile.  

Amabwiriza yimikorere yimikorere ya selile: ARA-290 igenga imikorere yingirabuzimafatizo nka macrophage. Muri vitro, ibuza gukora macrophage mugihe iteza imbere imikorere ya fagocytike yerekeza kuri selile apoptotique, ifasha kubungabunga sisitemu yumubiri homeostasis hamwe na selile apoptotique kugirango wirinde gutwikwa guterwa no kwirundanya kwabo (Dahan A, 2016). Mu bushakashatsi bwa aterosklerozose, ARA-290 ibuza kwimuka kwa macrophage no gukora ingirabuzimafatizo, kugabanya kugabanuka kwa lipide mu mitsi y'amaraso no gutinda kwa aterosklerose.

Uburyo bwa Neuroprotective Mechanism: Muburyo bwimbeba ya ischemia yubwonko, ARA-290 ikora ingaruka za neuroprotective binyuze muri β-reseptor rusange (βCR). Igabanya cyane ubwonko bwa apoptose na inflammatory cytokine mubice byubwonko, bigateza imbere imikorere yubwonko. Gutera inshinge siCR igamije siRNA irabuza cyane ingaruka za neuroprotective ARA-290, byerekana ko βCR igira uruhare runini mubikorwa byayo ^[3].  

Uburyo bwa Analgesic Mechanism: ARA-290 irashobora kugira ingaruka zo kubabaza no kwibasira nociceptors ya peripheri. Ubushakashatsi bwerekana ko bibuza cyane ibikorwa bya umuyoboro wa TRPV1 kandi bikagabanya imiterere ya allodynia ya capsaicin iterwa na capsaicin, byerekana ko ARA-290 ishobora kuba nk'igitabo gishya cyitwa TRPV1 antagonist, gitanga ubumenyi bushya bwo kuvura ububabare ^[4].  

Ni ubuhe buryo bukoreshwa muri ARA-290?

Kuvura Neuropathies

Kugabanya ububabare no kunoza ibimenyetso: ARA-290 igabanya neza ububabare bwa neuropathique, cyane cyane mu ndwara zifata ubwonko nka diyabete na sarcoidose. Mu bigeragezo by’amavuriro ku barwayi ba sarcoidose, ARA-290 yazamuye cyane ibimenyetso bya neuropathie n’ibimenyetso by’imitsi byigenga, byongera ubuzima bwiza, kandi bigabanya amanota y’ububabare, hamwe n’ingaruka nk'izo ku barwayi ba diyabete ya diabete. Uburyo bwabwo bukubiyemo guhuza ibyakiriwe neza (IRR), gukora inzira zo gusana anti-inflammatory na tissue inzira, kugenzura indwara ya neurogeneque, no kugabanya ububabare ^{[1, 4]}.

 

Guteza imbere imitsi ya Fibre Fibre: ARA-290 iteza imbere imitsi ya fibre. Ku barwayi ba sarcoidose, iminsi 28 ikurikiranye yo kuvura ARA-290 yatumye corneal ntoya ya fibre fibre ivugururwa, byerekana ubushobozi bwo gusana fibre yihariye ndetse nubushobozi bwo kunoza imikorere yimitsi, nubwo itagize ingaruka kumitsi ya epidermal nervice ^[1].  

Kugabanuka kwa Nephrotoxicity  

Kugabanuka kwa Cytotoxicity na Genotoxicity: Muri moderi ya cisplatine iterwa na nephrotoxicity, ARA-290 igabanya cyane cytotoxicity iterwa na cisplatine iterwa na cytotoxicity na genotoxicity, nko kugabanya ibipimo byangiza ADN mubisubizo byinyenyeri hamwe na micronucleus, kurinda ibikoresho bya selile no kugabanya kwangirika kwingirabuzimafatizo ^[1].

 

Kugena Stress ya Oxidative no Gutwika: ARA-290 itezimbere cisplatine iterwa na oxydeide igabanya urugero rwa malondialdehyde (MDA) na ROS no kongera ibikorwa bya enzyme ya antioxydeant. Igabanya kandi uburibwe bwimpyiko igabanya cytokine itera (urugero, TNF-α, IL-6, IL-1β), ikingira indwara yimpyiko iterwa na cisplatine ^. .  

Kubuza Apoptose: ARA-290 irabuza apoptose iterwa na cisplatine iterwa na genoside na poroteyine bifitanye isano na apoptose (urugero, kugabanya imvugo ya Caspase-3 na Bax, kongera imvugo ya Bcl-2), gukomeza kubaho kw'impyiko no kugira ubushobozi bwo kuvura abarwayi bakomeretse bikabije ^[1].  

Gutezimbere Ibimenyetso Byihebye  

Kugabanya Kwiheba-Imyitwarire: Muburyo bwimbeba zerekana imihangayiko idakira idateganijwe kandi ihangayikishijwe no gutsindwa kwabaturage, buri munsi ubuyobozi bwa ARA-290 bwateje imbere imyitwarire isa nihungabana, ugereranije na fluoxetine isanzwe igabanya ubukana. ARA-290 yagize ingaruka zo kurwanya antidepressant itagize ingaruka zikomeye kuri hemoglobine ya peripheri cyangwa selile zitukura ^[5].  

Kugena ingirangingo z'umubiri hamwe no gutwika: ARA-290 ihindura ubwiyongere bukabije buterwa no guhangayika kwiyongera inshuro n'umubare wa CD11b⁺Ly6Ghi neutrophile na CD11b⁺Ly6Chi monocytes yo mu magufa na meninges, ndetse no gukora mikorobe, kugabanya ibimenyetso byo kwiheba binyuze mu ngaruka zo kurwanya indwara no gutanga inzira nshya zo kuvura indwara yo kwiheba ^[5].  

Kurinda Indwara Yimpyiko  

Kubuza impyiko Epithelial Apoptose: ARA-290 ibuza impyiko yigituba epithelial selile apoptose, kugabanya urupfu rwa selile no kurinda ingirangingo.  

Kunoza imikorere yimpyiko: ARA-290 igabanya umuvuduko wo gusohora alubumu yinkari mu mbeba za diyabete, igabanya kwangirika kwimpyiko, kunoza imikorere yimpyiko, no gutinda kwa diabete ya nepropatique.  

Umuti wa Lupus Erythematosus (SLE)  

Kubuza umusaruro wa Autoantibody no Gutera Immune Complex: ARA-290 irabuza cyane antibody ya serumu antinuclear (ANA) hamwe na antibody ya ADN irwanya kabiri mu mbeba za SLE zatewe, kugabanya IgG na C3 mu mpyiko, kugabanya ibimenyetso bya neprite, no kunoza iterambere ry’indwara ^[6].  

Igicapo 1 Ubuvuzi bwa ARA290 bwahagaritse igisubizo kibabaza muri pristane - iterwa n'imbeba SLE. . . (C) Ibipimo by'intanga na lymph node byapimwe nyuma ya ARA290 ivura imbeba SLE (n = 6). Ibipimo bipima byerekana 30 mm.

Inkomoko: Byatangajwe ^[6]

Kugabanya Urwego Cytokine Yaka: ARA-290 igabanya serumu yibitekerezo bya cytokine IL-6, MCP-1, na TNF-α mu mbeba za SLE, bigabanya gucana no kugabanya ibimenyetso byindwara ^[6].  

Kugabanuka kwa Apoptose: ARA-290 igabanya umubare w'uturemangingo twa apoptotique mu mpyiko, ikingira ingirangingo z'impyiko, kandi ikabuza gukora macrophage mu gihe iteza imbere fagocytose y'uturemangingo twa apoptotique muri vitro, igenga imikorere y’umubiri kandi ifite ubushobozi bwo kuvura SLE ^[6].  

Kugabanya uburozi bwa chimiotherapeutique  

Kugabanya ibyangiritse kuri ADN: Muri moderi ya doxorubicine (DOX) yatewe na cytotoxicity, ARA-290 igabanya cyane kwangirika kwa ADN iterwa na DOX, nko kugabanya ijanisha rya ADN umurizo muri comet hamwe ninshuro ya micronucleus, kurinda ibintu bikomoka kuri selile no kugabanya imiti ya chimiotherapeutique yangiza selile zisanzwe ^[7].  

Kugabanya Stress ya Oxidative na Inflammation: ARA-290 igabanya kugabanuka kwa DOX iterwa no gukora ibikorwa bya enzyme ya antioxydeant, igabanya ubukana na apoptose, ikanarinda indwara ya okiside iterwa na DOX iterwa no kwangirika kw’uturemangingo, bishoboka ko harimo na selile z'umutima, kugira ngo igabanye ingaruka mbi ku barwayi ba chimiotherapie ^[7].  

Kwirinda no kuvura indwara ya Alzheimer  

Buhoro buhoro Iterambere rya Pathologiya no Kumenyekanisha Kunonosorwa: Ubuyobozi bwambere bwa ARA-290 mumbeba zikiri nto za APP / PS1 (moderi ya Alzheimer yo hambere) bidindiza β-amyloide (Aβ) gutera imbere kandi bigateza imbere imikorere yubwenge, bikerekana akamaro kayo mugutabara hakiri kare ^[8].

Amabwiriza yimikorere ya Monocyte: ARA-290 ishishikarizwa cyane cyane kubyara Ly6C⁻ irinda uduce duto twa monocyte, ikongera urugero rwikwirakwizwa ryayo, igatera Aβ gukuraho imiyoboro yamaraso yubwonko, kugabanya ubwonko bwa Aβ, kandi bidindiza iterambere ryindwara. Ariko, ntigikora neza mubyitegererezo bitinze (imbeba za APP / PS1 zishaje), bishimangira akamaro ko gutabara hakiri kare ^[8].  

Gutezimbere Gukiza Ibikomere bya Diyabete

Gufunga ibikomere byihuse: Muri streptozotocine iterwa na diyabete yindwara yimbeba yimbeba yimbeba, porogaramu ya ARA-290 yihutisha cyane gufunga ibikomere, bigabanya igihe cya reepithelialisation, kandi ikanakiza neza gukira ibikomere ^[9] .  

Kugena ibimenyetso byo gusana imyenda: ARA-290 yongerera kolagen na proteyine mu bice byo gusana, igenga insuline ya insuline, glucose yamaraso, urugero rwa lipide, imiterere ya antioxydeant, hamwe na cytokine itera inflammatory, bigashyiraho microen ibidukikije bifasha gukira ibikomere no gutanga ingamba nshya zo kuvura ibisebe bya diyabete ^[9].  

Kubabara  

Kubuza ibikorwa bya umuyoboro wa TRPV1: ARA-290 igabanya imiti ya allodynia ya capsaicine iterwa na capsaicin iterwa no guhagarika ibikorwa byumuyoboro wigihe gito wa vanilloid subtype 1 (TRPV1), yibasira byimazeyo nociceptors ya peripheri no gutanga uburyo bushya bwo kuvura hamwe nuburyo bwo kuvura ububabare ^[4].  

Umwanzuro  

ARA-290 ni polypeptide ikomoka kuri EPO ifite anti-inflammatory, anti-apoptotic, na anti-okiside. Irashobora kuvura ububabare bwa diyabete na sarcoidose, igatera fibre fibre kuvugurura, kurwanya nephrotoxicity, SLE, depression, no kugabanya ububabare mukurwanya TRPV1. Hamwe nibishoboka mugitangira cya Alzheimer hamwe nizindi nzego, ifite ibyifuzo byinshi byubuvuzi.

Ibyerekeye Umwanditsi

Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.

Umwanditsi w'ikinyamakuru

Al-Onaizi, Mohammed ni intiti ifite ubuhanga bwimbitse mubijyanye na biomedicine. Afitanye umubani yishyuwe nyuma ya 12 PM PST yoherejwe kumunsi wakazi ukurikira

Imirongo ijyanye

[1] Dahan A, Brines M, Niesters M, n'abandi. Kwibanda ku kuvura kuvuka kuvuka kuvura indwara ya neuropathie [J]. Raporo yububabare, 2016,1 (1): e566.DOI: 10.1097 / PR9.0000000000000566.

[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, n'abandi. Uburyo bukoreshwa muburyo bwo gukingira ingaruka za ARA290, Ligand yihariye ya Erythropoietin / CD131 Heteroreceptor, kurwanya Cisplatine iterwa na Nephrotoxicity, Uruhare rwa Apoptose ninzira Zitwika [J]. Gutwika, 2023.46 (1): 342-358.DOI: 10.1007 / s10753-022-01737-7.

[3] Wang R, Yang Z, Huang Y, n'abandi. Erythropoietin - ikomoka kuri peptide ARA290 ihuza kurinda ubwonko bwubwonko binyuze muri $ beta $ ‐ibisanzwe byakira imbeba hamwe nubwonko bwubwonko bwubwonko [J]. CNS Neuroscience & Ubuvuzi, 2024,30. https://api.semanticscholar.org/CorpusID:268414491.

4 Peptide, 2016,76: 73-79.DOI: 10.1016 / j.peptides.2016.01.003.

[5] Xu G, Zou T, Deng L, n'abandi. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ihindura Imyitwarire idakira Yatewe no kwiheba-Imyitwarire no gutwika imbeba [J]. Imipaka muri Farumasi, 2022,13: 896601.

DOI: 10.3389 / fphar.2022.896601.

[6] Huang B, Jiang J, Luo B, n'abandi. Non-erythropoietic erythropoietin ikomoka kuri peptide irinda imbeba sisitemu ya lupus erythematosus [J]. Ikinyamakuru cyubuvuzi bwa selile na molecular, 2018,22 (7): 3330-3339.DOI: 10.1111 / jcmm.13608.

[7] Shokrzadeh M, Etebari M, Ghassemi-Barghi N. Peptide ikomoka kuri erythropoietic yakozwe na peptide, ARA290, ihuza doxorubicine itera genotoxicity hamwe na stress ya okiside [J]. Uburozi muri Vitro, 2020,66: 104864.

DOI: 10.1016 / j.tiv.2020.104864.

[8] Al-Onaizi MA, Thériault P, Lecordier S, n'abandi. Guhindura monocyte hakiri kare na peptide itari erythropoietic ARA 290 yihutisha iterambere rya AD rimeze nka patologiya [J]. Imyitwarire y'ubwonko n'ubudahangarwa, 2022,99: 363-382.

DOI: 10.1016 / j.bbi.2021.07.016.

[9] Mashreghi M, Bayrami Z, Sichani N, n'abandi. Iperereza ryakozwe na vivo kubikorwa byo gukiza ibikomere bya ligand yihariye ya reseptor yo gusana ivuka, ARA290, ukoresheje icyitegererezo cyinyamaswa ya diyabete [M]. 2023.DOI: 10.21203 / rs.3.rs-2520194 / v1.

INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.  

Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.