ARA-290 16mg

▎ ya ARA-290 Enzimba

Ensibuko: PubChem

Omutendera: XEQLERALNSS Ensengekera ya molekyu: C 51H 84N 16O21 Obuzito bwa molekyu: 1257.3g/mol Ennamba ya CAS:1208243-50-8 Ekitongole kya PubChem CID:91810664 Ebigambo ebifaanagana: Cibinetide

▎ ~!phoenix_var93_1!~ Okunoonyereza kwa

Ensibuko y’okunoonyereza ku ARA-290 eri etya?  

Enkulaakulana ya ARA-290 yasibuka mu kunoonyereza ku busobozi bw’obujjanjabi bwa erythropoietin (EPO). Bannasayansi baakizudde nti EPO tekoma ku kutumbula erythropoiesis wabula erina n’emirimu gy’okukuuma ebitundu by’omubiri ng’okuziyiza okuzimba n’okuziyiza okufa kw’omubiri. Wabula, okusikirizibwa kwa EPO okukola omusaayi kuyinza okwongera ku buzito bw’omusaayi n’obulabe obulala, ne kikoma ku kukozesebwa kwayo mu kujjanjaba endwadde ezitali za musaayi. Okusobola okukuuma ebikolwa bya EPO ebikuuma ebitundu by’omubiri ate nga beewala ebizibu byayo eby’okukola omusaayi, abanoonbereza baatandika okukola dizayini ya peptides ezivaamu, ekyaviirako okutondebwawo kwa ARA-290.  

Nga waliwo okunoonyereza okw’amaanyi, ebirungi eby’enjawulo ebya ARA-290 nga peptide etali ya musaayi byamanyibwa mpolampola. Ekola amakubo g’obubonero obuziyiza okuzimba n’okuddaabiriza ebitundu by’omubiri nga yesiba ku kirungo ekizaalibwamu okuddaabiriza (IRR), ekiraga ebisuubiza mu kujjanjaba ebizibu bya ssukaali, obulwadde bw’obusimu, n’obuvune bw’ekibumba. Ebizuuliddwa bino byassaawo omusingi gw’okwongera okunoonyereza n’okukozesa ARA-290 mu bujjanjabi era ne bitumbula okukola enkola empya ez’obujjanjabi ezesigamiziddwa ku peptides ezisibuka mu EPO.  

Enkola ki ey’okukola kwa ARA-290?  

Anti-Inflammatory Effect: ARA-290 eziyiza okufulumya kwa cytokines ezizimba, bwe kityo n’ekendeeza ku kuddamu kw’okuzimba, nga bwe kiragibwa mu bikolwa by’endwadde eziwera. Okugeza, mu muze gw’ebibe ogwa systemic lupus erythematosus (SLE), kikendeeza ku serum concentrations ya inflammatory cytokines IL-6, MCP-1, ne TNF-α, okulongoosa obubonero bwa SLE{#Dahan, A,2016} (Dahan A, 2016). Mu nkola ya cisplatin-induced nephrotoxicity model, ekendeeza pro-inflammatory cytokines TNFα, IL6, ne IL1β, okukendeeza ku kuzimba kw’ekibumba ^[2] ( Ghassemi-Barghi N, 2023 ). Enkola yaayo ey’okuziyiza okuzimba eyinza okuzingiramu okutunuulira ekirungo ekizaalibwa mu kuddaabiriza (IRR), heterodimer y’ekirungo ekikwata erythropoietin n’ekirungo kya β-common (CD131). Okusiba ku IRR kikola amakubo g’obubonero obuziyiza okuzimba wansi, bwe kityo ne kikendeeza ku kuzimba ^[1]..

Anti-Apoptotic Effect: ARA-290 eziyiza okufa kw’obutoffaali era etumbula obulamu bw’obutoffaali bw’ebitundu. Mu nkola y’envunza eya sukaali, enyigiriza okufa kw’obutoffaali bw’ekibumba obuyitibwa renal tubular epithelial cell apoptosis era n’ekendeeza ku kwolesebwa kwa proteases enkulu mu nkola ya apoptotic, bwe kityo ne kikola ebikolwa eby’okukuuma ekibumba. Mu bikolwa by’obutwa obuleetebwa cisplatin, kitereeza okwolesebwa kwa puloteyina ezikwatagana n’okufa nga Bax ne Bcl-2, kiziyiza emirimu gya Caspase-3, kikendeeza ku kufa kw’obutoffaali, era kikendeeza ku kwonooneka kw’obutoffaali bw’ekibumba obuva ku cisplatin ^[2]..  

Anti-Oxidative Effect: ARA-290 eziyiza okwonooneka kwa oxidative stress era ekendeeza ku kukola ebintu eby’obulabe nga reactive oxygen species (ROS). Mu nkola y’ekibumba ky’envunza eya ssukaali, enyigiriza okulaga kw’obuzaale bw’ekibumba, ekendeeza ku miwendo gya ROS mu kibumba, era ekendeeza ku kwolesebwa kwa malondialdehyde (MDA), okukendeeza ku kwonooneka kw’ekibumba okuva ku situleesi ya oxidative. Mu kunoonyereza ku kuzimba emisuwa, okugezesa mu vitro kulaga nti ARA-290 eziyiza okukola ROS mu macrophages wansi w’embeera z’okuzimba, okukendeeza ku kwonooneka kwa oxidative stress eri obutoffaali.  

Okulungamya enkola y’obutoffaali obuziyiza endwadde: ARA-290 etereeza enkola y’obutoffaali bw’abaserikale b’omubiri nga macrophages. Mu vitro, kiziyiza okuzimba okukola kwa macrophages ate nga kitumbula omulimu gwazo ogwa phagocytic eri obutoffaali obufa, okuyamba okukuuma abaserikale b’omubiri homeostasis n’okulongoosa obutoffaali bwa apoptotic okwewala okuzimba okuva ku kukuŋŋaanyizibwa kwabwo (Dahan A, 2016). Mu kunoonyereza ku kuzimba emisuwa, ARA-290 eziyiza okutambula kwa macrophage n’okutondebwa kw’obutoffaali bwa foam, okukendeeza ku kuteekebwa kw’amasavu mu intima y’emisuwa n’okukendeeza ku kukula kw’okuzimba emisuwa.

Enkola y’okukuuma obusimu: Mu nkola y’ebibe ey’okukendeera kw’omusaayi mu bwongo, ARA-290 ekola ebikolwa eby’okukuuma obusimu okuyita mu β-common receptor (βCR). Kikendeeza nnyo ku apoptosis y’obusimu n’emiwendo gya cytokine ezizimba mu bitundu by’obwongo, okulongoosa enkola y’obusimu. Empiso ya βCR-targeted siRNA kiziyiza nnyo ARA-290's neuroprotective effects, ekiraga nti βCR ekola kinene mu nkola yaayo ^[3]..  

Enkola y’okukendeeza obulumi: ARA-290 eyinza okukola ebikolwa eby’okukendeeza obulumi ng’etunuulira butereevu ebirungo ebiwunyiriza eby’okumpi. Okunoonyereza kulaga nti kiziyiza mu ngeri ey’enjawulo emirimu gy’omukutu gwa TRPV1 era kikendeeza ku capsaicin-induced mechanical allodynia, ekiraga nti ARA-290 eyinza okukola nga novel TRPV1 channel antagonist, okuwa amagezi amapya ku kujjanjaba obulumi ^[4]..  

Enkozesa ya ARA-290 ze ziruwa?

Obujjanjabi bw’obulwadde bw’obusimu

Okukendeeza obulumi n’okulongoosa obubonero: ARA-290 ekendeeza bulungi obulumi bw’obusimu naddala mu ndwadde ezirina obulwadde bw’obusimu nga sukaali ne sarcoidosis. Mu kugezesebwa okw’obujjanjabi ku balwadde ba sarcoidosis, ARA-290 yalongoosa nnyo obubonero bw’obusimu n’obusimu obukola emirimu egy’enjawulo, yayongera ku mutindo gw’obulamu, n’okukendeeza ku bubonero bw’obulumi, n’ebikolwa ebifaanagana mu balwadde b’obusimu bwa sukaali. Enkola yaayo erimu okusiba ku innate repair receptor (IRR), okukola amakubo agaziyiza okuzimba n’okuddaabiriza ebitundu, okulungamya okuzimba kw’obusimu, n’okukendeeza obulumi ^{[1, 4].}.

 

Okutumbula okuddamu okukola obusimu: ARA-290 etumbula okuddamu okukola obusimu. Mu balwadde ba sarcoidosis, ennaku 28 ez’omuddiring’anwa ez’obujjanjabi bwa ARA-290 zaaleeta okuddamu okukola obusimu obutono obw’omu maaso, nga kiraga obusobozi bw’okuddaabiriza obuwuzi bw’obusimu obw’enjawulo n’obusobozi okulongoosa enkola y’obusimu, wadde nga tekyalina kye kyakola ku busimu bw’olususu ^[1]..  

Okukendeeza ku butwa bwa Nephrotoxicity  

Oka bw’obut’obutwa bw’obutoffaali n’obutwa mu bitundu by’omubiri: Mu biby’omubiri: Mu bikolwa by’obutwa mu kibumba obuleetebaa cisplatin, ARA-290 ekendeeza nnyo obutwa obuleetebwa cisplatin n’obutwa mu^{~!phoenix_var109_1!~}.

 

Okulungamya Oxidative Stress n’okuzimba: ARA-290 erongoosa cisplatin-induced oxidative stress nga ekendeeza ku malondialdehyde (MDA) ne ROS levels n’okutumbula antioxidant enzyme activity. Era kikendeeza ku kuzimba kw’ekibumba nga kikendeeza ku cytokines eziyamba okuzimba (okugeza, TNF-α, IL-6, IL-1β), okukuuma obuvune bw’ekibumba obuva ku cisplatin ^[1]. .  

Okuziyiza Apoptosis: ARA-290 eziyiza cisplatin-induced apoptosis nga elungamya obuzaale ne puloteyina eyeekuusa ku apoptosis (okugeza, okukendeeza ku Caspase-3 ne Bax expression, okwongera Bcl-2 expression), okukuuma obulamu bw’obutoffaali bw’ekibumba n’okukuuma obusobozi okujjanjaba abalwadde abalumwa ekibumba ^{[1] .}.  

Okulongoosa Obubonero bw’Okwennyamira  

Okukendeeza ku nneeyisa eringa okwennyamira: Mu bikolwa by’ebibe eby’okunyigirizibwa okutali kwa bulijjo okutategeerekeka n’okunyigirizibwa okw’okuwangulwa mu bantu okutambula, okuweebwa ARA-290 buli lunaku kwalongoosa enneeyisa eringa ey’okwennyamira, okugeraageranyizibwa ku ddagala erya bulijjo eriziyiza okwennyamira erya fluoxetine. ARA-290 yakola eddagala eriweweeza ku kweraliikirira nga tekosezza nnyo hemoglobin ey’okumpi oba obutoffaali obumyufu ^[5]..  

Okulungamya obutoffaali bw’abaserikale b’omubiri n’okuzimba: ARA-290 ezzaawo okweyongera okuva ku situleesi okutawona mu mirundi n’omuwendo gwa CD11b+Ly6Ghi neutrophils ne CD11b+Ly6Chi monocytes mu busimu bw’amagumba ne meninges, wamu n’okukola microglial, okukendeeza ku bubonero bw’okwennyamira okuyita mu bikolwa ebiziyiza okuzimba n’okuwa obujjanjabi obupya amakubo g’okwennyamira ^{[5] .}.  

Obukuumi Ku Ssukaali Okwonooneka Ekibumba  

Okuziyiza okufa kw’obutoffaali bw’ekibumba: ARA-290 eziyiza okufa kw’obutoffaali bw’ekibumba obuyitibwa renal tubular epithelial cell apoptosis, okukendeeza ku kufa kw’obutoffaali okutegekeddwa n’okukuuma obutoffaali bw’ekibumba.  

Okulongoosa obubonero bw’enkola y’ekibumba: ARA-290 ekendeeza ku muwendo gw’okufulumya albumin mu musulo mu nvunza ezirina ssukaali, ekendeeza ku kwonooneka kw’endwadde z’ekibumba, etereeza enkola y’ekibumba, n’okulwawo okukula kw’obulwadde bwa sukaali.  

Obujjanjabi bw’obulwadde bwa Systemic Lupus Erythematosus (SLE) .  

Okuziyiza okukola Autoantibody n’okuteekebwa kw’obusimu obuziyiza endwadde: ARA-290 eziyiza nnyo emiwendo gy’obuziyiza bwa serum antinuclear antibody (ANA) ne anti-double-stranded DNA antibody mu mbeba ezireetebwa SLE, ekendeeza ku kuteekebwa kwa IgG ne C3 mu nsigo, ekendeeza ku bubonero bw’obulwadde bw’ekibumba, era etereeza enkulaakulana y’obulwadde ^[6]..  

Ekifaananyi 1 Obujjanjabi bwa ARA290 bwanyigiriza okuddamu kw’okuzimba mu mbeba za SLE ezireetebwa pristane. (A) Emiwendo gya IL‐6, IL‐10, MCP‐1, IFN‐γ, TNF‐α, IL‐12p70 ne TGF‐β mu serum oluvannyuma lw’obujjanjabi obwayogerwako mu kifaananyi 1 gyazuulibwa (n = 6). (B) Okuyingira kwa macrophage F4/80 okuzimba kwali kunyigirizibwa nnyo olw’okuyingira mu nsonga za ARA 290 bw’ogeraageranya n’okufuga PBS. (C) Obuzito bw’ennywanto n’ennywanto zapimibwa oluvannyuma lw’okujjanjaba ARA290 mu mbeba za SLE (n = 6). Embaawo za minzaani zikiikirira 30 μm.

Ensibuko:PubMed ^{[6] .}

Okukendeeza ku miwendo gya Inflammatory Cytokine: ARA-290 ekendeeza ku serum concentrations ya inflammatory cytokines IL-6, MCP-1, ne TNF-α mu mbeba za SLE, okukendeeza ku kuzimba n’okukendeeza ku bubonero bw’obulwadde ^[6]..  

Okukendeera mu Apoptosis: ARA-290 ekendeeza ku muwendo gw’obutoffaali obufa mu nsigo, ekuuma obutoffaali bw’ekibumba, era eziyiza okukola kw’okuzimba kwa macrophages ate nga etumbula phagocytosis yaabwe ey’obutoffaali obufa mu vitro, okulungamya abaserikale b’omubiri n’okukwata obusobozi bw’obujjanjabi bwa SLE ^[6]..  

Okukendeeza ku butwa bw’eddagala eriweweeza ku bulwadde bwa Chemotherapeutic  

Okukendeeza ku kwonooneka kwa DNA: Mu bikolwa by’obutwa obuleetebwa doxorubicin (DOX), ARA-290 ekendeeza nnyo ku kwonooneka kwa DNA okuleetebwa DOX, gamba ng’okukendeeza ku bitundu bya DNA y’omukira mu kukebera kwa comet ne micronucleus frequency, okukuuma obuzaale bw’obutoffaali n’okukendeeza ku kwonooneka kw’eddagala eri obutoffaali obwa bulijjo ^{[7] .}.  

Okukendeeza ku situleesi ya Oxidative n’okuzimba: ARA-290 ekendeeza ku buzibu obuva mu DOX mu mirimu gy’enziyiza y’obuwuka, ekendeeza ku kuzimba n’okufa kw’obutoffaali, era ekuuma okuva ku situleesi y’okwokya n’obutoffaali obuleetebwa DOX, ekiyinza okuli n’obutoffaali bw’omutima, okukendeeza ku bikolwa ebibi mu balwadde abaweebwa eddagala ^{[7] .}.  

Okuziyiza n'okujjanjaba obulwadde bwa Alzheimer's  

Slowed Pathological Progression and Improved Cognition: Okugaba ARA-290 nga bukyali mu mbeba ento APP/PS1 (early Alzheimer’s model) kikendeeza ku β-amyloid (Aβ) pathological progression era kitereeza enkola y’okutegeera, okulaga obukulu bwayo mu kuyingira mu nsonga nga bukyali ^[8]..

Regulation of Monocyte Function: ARA-290 mu ngeri ey’enjawulo esitula okuzaala Ly6C− patrolling monocyte subsets, eyongera ku miwendo gyazo egy’okutambula, etumbula Aβ clearance okuva mu misuwa gy’omusaayi mu bwongo, ekendeeza ku buzito bwa Aβ obw’obwongo, era elwawo okukulaakulana kw’obulwadde. Wabula, tekikola nnyo mu bikolwa eby’omutendera ogusembayo (ebibe eby’emyaka egy’APP/PS1), ekiggumiza obukulu bw’okuyingira mu nsonga nga bukyali ^[8]..  

Okutumbula okuwona ebiwundu bya sukaali

Okuggalawo ebiwundu mu bwangu: Mu bikolwa by’envunza ezisaliddwako ssukaali, okukozesa ARA-290 mu kitundu kyangu nnyo okuggalawo ebiwundu, kikendeeza ku budde bw’okuddamu okukola ebiwundu, n’okulongoosa obulungi bw’okuwona ebiwundu ^[9]. .  

Okulungamya obubonero bw’okuddaabiriza ebitundu: ARA-290 eyongera ku kolagini ne puloteyina mu bitundu ebiddaabiriza, etereeza insulini mu musaayi, glucose mu musaayi, emiwendo gy’amasavu, embeera y’ekiziyiza obuwuka, n’emiwendo gya cytokine eyamba okuzimba, okutondawo embeera entonotono eyamba okuwona ebiwundu n’okuwa obukodyo obupya obw’okujjanjaba amabwa g’ebigere aga ssukaali ^[9].  

Okukendeeza ku bulumi  

Okuziyiza emirimu gy’omukutu gwa TRPV1: ARA-290 ewummuza capsaicin-induced mechanical allodynia nga eziyiza transient receptor potential vanilloid subtype 1 (TRPV1) channel activity, butereevu okutunuulira peripheral nociceptors n’okuwa ebigendererwa ebipya eby’obujjanjabi n’enkola z’okujjanjaba obulumi ^[4]..  

Mu bufunzi  

ARA-290 ye polypeptide evudde mu EPO ng’erina ebikolwa ebiziyiza okuzimba, okuziyiza okufa, n’okuziyiza okuzimba. Kisobola okujjanjaba obulumi mu ssukaali ne sarcoidosis, okutumbula okuddamu okukola kw’obusimu, okulwanyisa obutwa mu kibumba, SLE, okwennyamira, n’okukendeeza ku bulumi nga kiziyiza TRPV1. Nga erina obusobozi mu kuyingira mu nsonga z’obulwadde bwa Alzheimer nga bukyali n’emirimu emirala, erina essuubi erigazi ery’okukozesa mu bujjanjabi.

Ebikwata ku Muwandiisi

Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.

Omuwandiisi wa Scientific Journal

Al-Onaizi, Mohammed mumanyi alina obukugu obw’amaanyi mu by’obujjanjabi bw’ebiramu. Alina enkolagana ey’oku lusegere n’amatendekero agamanyiddwa ennyo mu by’ensoma n’okunoonyereza, omuli Dasman Diabetes Institute (DDI), Kuwait University, Laval University, Western University (University of Western Ontario), ne Hebrew University of Jerusalem. Okunoonyereza kwe kugazi, nga kukwata ku Neurosciences & Neurology, Biochemistry & Molecular Biology, Immunology, Psychiatry, n’emitwe emirala mu Life Sciences & Biomedicine. Emisomo gino gikulu nnyo okusobola okufuna okutegeera okw’amaanyi ku nkola z’omubiri gw’omuntu, enkola y’endwadde, n’okukola obujjanjabi obupya. Al-Onaizi, okunoonyereza kwa Mohammed kutuuse ku bivuddemu ebikulu mu ssaayansi omusingi era kuwadde obuwagizi obukulu obw’enzikiriziganya n’obulagirizi obw’omugaso eri eddagala ly’obujjanjabi n’okunoonyereza ku by’obulamu.. Al-Onaizi, Mohammed is listed in the reference of citation [8].

▎ Ebiwandiiko Ebikwatagana

[1] Dahan A, Brines M, Niesters M, n’abalala. Okutunuulira ekirungo ekizaalibwamu eky’okuddaabiriza okujjanjaba obulwadde bw’obusimu[J]. Lipoota z’obulumi, 2016,1 (1)

[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, n’abalala. Enkola ey’enkola ey’okukuuma ARA290, Ligand Entongole eri Erythropoietin/CD131 Heteroreceptor, ku Cisplatin-Induced Nephrotoxicity, okwenyigira mu Apoptosis n’amakubo g’okuzimba[J]. Okuzimba, 2023, 46 (1): 342-358.DOI: 10.1007 / s10753-022-01737-7.

[3] Wang R, Yang Z, Huang Y, n’abalala. Erythropoietin‐derived peptide ARA290 etabaganya okukuuma ebitundu by’obwongo okuyita mu $eta$‐common receptor mu mbeba ezirina cerebral ischemic stroke[J]. CNS Neuroscience & Obujjanjabi, 2024,30. https://api.semanticscholar.org/CorpusID:268414491. Enkola y’okukuuma obutonde bw’ensi.

[4] Zhang W, Yu G, Zhang M. ARA 290 ewummuza obulumi obw’omubiri nga etunuulira omukutu gwa TRPV1: Okugatta wakati w’abaserikale b’omubiri n’okuwulira obulumi[J]. Peptides, 2016,76:73-79.DOI:10.1016/j.peptides.2016.01.003.

[5] Xu G, Zou T, Deng L, n’abalala. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Etereeza Enneeyisa y’Okwennyamira Okuva ku Situleesi Okutawona n’okuzimba mu mbeba[J]. Ensalo mu by’eddagala, 2022,13:896601.

DOI:10.3389/fphar.2022.896601.

[6] Huang B, Jiang J, Luo B, n’abalala. Peptide evudde mu erythropoietin etali ya erythropoietic ekuuma ebibe okuva ku systemic lupus erythematosus[J]. Journal of Eddagala ly'obutoffaali ne molekyu, 2018,22 (7): 3330-3339.DOI: 10.1111 / jcmm.13608.

[7] Shokrzadeh M, Etebari M, Ghassemi-Barghi N. Peptide eya yinginiya etali ya erythropoietic erythropoietin-derived peptide, ARA290, ekendeeza doxorubicin induced genotoxicity ne oxidative stress[J]. Obutwa mu Vitro, 2020,66:104864.

DOI:10.1016/j.tiv.2020.104864.

[8] Al-Onaizi M. A., Thériault P., Lecordier S., n’abalala. Okukyusa monocyte nga bukyali nga peptide etali ya erythropoietic ARA 290 ekendeeza ku kukula kw’obulwadde obulinga AD[J]. Enneeyisa y'obwongo n'obusimu obuziyiza endwadde, 2022,99:363-382.

DOI:10.1016/j.bbi.2021.07.016.

[9] Mashreghi M, Bayrami Z, Sichani N, n’abalala. Okunoonyereza mu vivo ku mirimu gy’okuwonya ebiwundu egya Specific ligand for the innate repair receptor, ARA290, nga tukozesa ekifaananyi ky’ekisolo kya sukaali[M]. 2023.DOI:10.21203/rs.3.rs-2520194/v1.

EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.  

Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.