ARA-290 16 mg

▎ ARA-290 Qauv

Source: PubChem

Sequence: XEQLERALNSS Molecular Formula: C 51H 84N 16O21 Molecular Luj: 1257.3g/mol CAS Nr .: 1208243-50-8 PubChem CID: 91810664 Synonyms: Cibinetide

▎ ARA-290 Kev Tshawb Fawb

Kev tshawb fawb keeb kwm ntawm ARA-290 yog dab tsi?  

Txoj kev loj hlob ntawm ARA-290 pib los ntawm kev tshawb nrhiav cov peev xwm kho mob ntawm erythropoietin (EPO). Cov kws tshawb fawb pom tias EPO tsis yog tsuas yog txhawb nqa erythropoiesis tab sis kuj muaj cov ntaub so ntswg tiv thaiv kev ua haujlwm xws li tiv thaiv kab mob thiab tiv thaiv apoptosis. Txawm li cas los xij, EPO's hematopoietic stimulation yuav ua rau kom ntshav viscosity thiab lwm yam kev pheej hmoo, txwv tsis pub nws siv los kho cov kab mob uas tsis yog anemic. Txhawm rau khaws EPO cov ntaub so ntswg-tiv thaiv cov teebmeem thaum zam nws cov kev mob tshwm sim hematopoietic, cov kws tshawb fawb tau pib tsim cov derivative peptides, ua rau kev tsim ntawm ARA-290.  

Nrog rau kev tshawb fawb tob, qhov tshwj xeeb zoo ntawm ARA-290 raws li cov tsis-hematopoietic peptide tau maj mam lees paub. Nws activates anti-inflammatory thiab cov ntaub so ntswg kho cov teeb liab txoj kev los ntawm kev khi rau lub innate kho receptor (IRR), qhia tau hais tias muaj txiaj ntsig zoo hauv kev kho mob ntshav qab zib, neuropathies, thiab mob raum. Cov kev tshawb pom no tau tsim lub hauv paus rau kev tshawb fawb ntxiv thiab kev siv tshuaj kho mob ntawm ARA-290 thiab txhawb kev txhim kho cov tswv yim kho tshiab raws li EPO-derived peptides.  

Lub mechanism ntawm kev txiav txim ntawm ARA-290 yog dab tsi?  

Anti-Inflammatory Effects: ARA-290 inhibits qhov tso tawm ntawm inflammatory cytokines, yog li txo cov inflammatory teb, raws li pom nyob rau hauv ntau yam kab mob qauv. Piv txwv li, hauv tus qauv nas ntawm cov kab mob lupus erythematosus (SLE), nws txo cov ntshav cov ntshav ntawm cov cytokines IL-6, MCP-1, thiab TNF-α, txhim kho SLE cov tsos mob {#Dahan, A, 2016} (Dahan A, 2016). Hauv cov qauv cisplatin-induced nephrotoxicity, nws txo qis pro-inflammatory cytokines TNFα, IL6, thiab IL1β, alleviating raum mob ^[2] (Ghassemi-Barghi N, 2023). Nws cov txheej txheem tiv thaiv kab mob tuaj yeem koom nrog kev tsom mus rau kev kho tus neeg mob lub cev (IRR), heterodimer ntawm erythropoietin receptor thiab β-common (CD131) receptor. Kev khi rau IRR activates downstream anti-inflammatory signaling pathways, li no downregulating o ^[1].

Anti-Apoptotic Effects: ARA-290 inhibits cell apoptosis thiab txhawb nqa cov ntaub so ntswg ciaj sia. Nyob rau hauv tus qauv nas mob ntshav qab zib, nws suppresses lub raum tubular epithelial cell apoptosis thiab txo qhov kev qhia ntawm cov proteases tseem ceeb hauv cov txheej txheem apoptotic, yog li ua rau lub raum tiv thaiv. Hauv cov qauv cisplatin-induced nephrotoxicity, nws tswj cov kev qhia ntawm apoptosis-txog cov proteins xws li Bax thiab Bcl-2, inhibits Caspase-3 kev ua, txo cov cell apoptosis, thiab txo qis cisplatin-vim lub raum puas hlwb ^[2].  

Anti-Oxidative Effects: ARA-290 inhibits oxidative kev nyuaj siab puas tsuaj thiab txo cov khoom tsim teeb meem xws li reactive oxygen hom (ROS). Nyob rau hauv tus qauv nas mob ntshav qab zib mellitus, nws inhibits lub raum noob qhia, txo lub raum ROS theem, thiab txo qis malondialdehyde (MDA) qhia, alleviating oxidative stress-induced raum puas. Hauv kev tshawb fawb atherosclerosis, kev sim hauv vitro qhia tau hais tias ARA-290 inhibits ROS ntau lawm hauv macrophages nyob rau hauv cov mob inflammatory, txo oxidative kev nyuaj siab rau cov hlwb.  

Kev tswj hwm lub cev tiv thaiv kab mob: ARA-290 tswj kev ua haujlwm ntawm lub cev tiv thaiv kab mob xws li macrophages. Nyob rau hauv vitro, nws inhibits inflammatory activation ntawm macrophages thaum txhawb lawv phagocytic muaj nuj nqi rau apoptotic hlwb, pab tswj lub cev tiv thaiv kab mob homeostasis thiab ntshiab apoptotic hlwb kom tsis txhob mob los ntawm lawv tsub zuj zuj (Dahan A, 2016). Hauv kev tshawb fawb atherosclerosis, ARA-290 inhibits macrophage migration thiab ua npuas ncauj cell tsim, txo lipid deposition nyob rau hauv vascular intima thiab slowing atherosclerosis.

Neuroprotective Mechanism: Hauv nas qauv ntawm cerebral ischemia, ARA-290 exerts neuroprotective teebmeem los ntawm β-common receptor (βCR). Nws txo qis neuronal apoptosis thiab inflammatory cytokine theem nyob rau hauv lub hlwb cov ntaub so ntswg, txhim kho neurological muaj nuj nqi. Kev txhaj tshuaj ntawm βCR-targeted siRNA cuam tshuam ARA-290's neuroprotective teebmeem, qhia tias βCR plays lub luag haujlwm tseem ceeb hauv nws cov txheej txheem ^[3].  

Analgesic Mechanism: ARA-290 tuaj yeem ua rau muaj kev phom sij los ntawm kev tsom ncaj qha rau peripheral nociceptors. Kev tshawb fawb qhia tias nws tshwj xeeb inhibits TRPV1 channel kev ua si thiab alleviates capsaicin-induced mechanical allodynia, tawm tswv yim ARA-290 tuaj yeem ua tus tshiab TRPV1 channel antagonist, muab kev nkag siab tshiab rau kev kho mob ^[4].  

Dab tsi yog cov ntawv thov ntawm ARA-290?

Kev kho mob ntawm Neuropathies

Pain Relief and Symptom Improvement: ARA-290 zoo relieves mob neuropathic, tshwj xeeb tshaj yog nyob rau hauv cov kab mob nrog neuropathy xws li ntshav qab zib thiab sarcoidosis. Hauv kev sim tshuaj rau cov neeg mob sarcoidosis, ARA-290 tau txhim kho neuropathy thiab cov tsos mob ntawm lub paj hlwb, txhim kho lub neej zoo, thiab txo qhov mob, nrog rau cov txiaj ntsig zoo sib xws hauv cov neeg mob ntshav qab zib neuropathy. Nws cov txheej txheem cuam tshuam nrog kev khi rau lub cev kho qhov muag (IRR), ua kom muaj kev tiv thaiv kab mob thiab kho cov ntaub so ntswg, tswj cov kab mob neurogenic, thiab txo qhov mob ^{[1, 4]}.

 

Kev txhawb nqa ntawm Nerve Fiber Regeneration: ARA-290 txhawb nqa paj hlwb rov tsim dua tshiab. Hauv cov neeg mob sarcoidosis, 28 hnub sib law liag ntawm ARA-290 kev kho mob induced corneal me paj hlwb regeneration, qhia txog kev kho lub peev xwm rau cov paj hlwb tshwj xeeb thiab muaj peev xwm los txhim kho neurological muaj nuj nqi, txawm hais tias nws tsis cuam tshuam rau epidermal paj fibers ^[1].  

Kev txo qis ntawm Nephrotoxicity  

Txo Cytotoxicity thiab Genotoxicity: Hauv cov qauv cisplatin-induced nephrotoxicity, ARA-290 txo qis cisplatin-induced cytotoxicity thiab genotoxicity, xws li txo DNA kev puas tsuaj tsis nyob rau hauv comet assay thiab micronucleus zaus, tiv thaiv cellular puas genetic khoom thiab renal ^..

 

Kev tswj ntawm Oxidative Stress thiab Inflammation: ARA-290 txhim kho cisplatin-induced oxidative kev nyuaj siab los ntawm kev txo cov malondialdehyde (MDA) thiab ROS qib thiab pab txhawb kev ua haujlwm antioxidant. Nws kuj alleviates raum mob los ntawm kev txo qis pro-inflammatory cytokines (xws li, TNF-α, IL-6, IL-1β), tiv thaiv cisplatin-induced raum raug mob ^[1] .  

Inhibition of Apoptosis: ARA-290 inhibits cisplatin-induced apoptosis los ntawm kev tswj cov noob caj noob ces thiab cov proteins (xws li, txo qis Caspase-3 thiab Bax qhia, nce Bcl-2 qhia), tswj lub raum cell ciaj sia thiab tuav lub peev xwm los kho cov neeg mob raum raug mob ^[1].  

Txhim kho cov tsos mob ntawm kev nyuaj siab  

Kev txo qis ntawm Kev Nyuaj Siab Zoo Li Tus Cwj Pwm: Hauv cov qauv nas ntawm qhov tsis muaj kev ntxhov siab me me thiab kev ntxhov siab ntev hauv kev sib raug zoo, kev tswj hwm ARA-290 txhua hnub tau txhim kho tus cwj pwm zoo li kev nyuaj siab, piv rau cov tshuaj tiv thaiv kev nyuaj siab fluoxetine. ARA-290 tau siv tshuaj tiv thaiv kev nyuaj siab yam tsis muaj kev cuam tshuam rau peripheral hemoglobin lossis cov qe ntshav liab ^[5].  

Kev tswj hwm ntawm Immune Cells thiab Inflamation: ARA-290 thim rov qab cov kev ntxhov siab ntev-ntxias nce hauv zaus thiab tus naj npawb ntawm CD11b⁺Ly6Ghi neutrophils thiab CD11b⁺Ly6Chi monocytes hauv cov pob txha pob txha thiab meninges, nrog rau cov kab mob microglial activation los ntawm kev kho mob tshiab, txhua yam kev mob tshwm sim. kev nyuaj siab ^[5].  

Kev Tiv Thaiv Kab Mob Ntshav Qab Zib raum puas  

Inhibition ntawm lub raum Tubular Epithelial Apoptosis: ARA-290 inhibits lub raum tubular epithelial cell apoptosis, txo cov txheej txheem cell tuag thiab tiv thaiv lub raum hlwb.  

Kev txhim kho lub raum Kev Ua Haujlwm Cov Cim: ARA-290 txo qis cov zis albumin tso tawm hauv cov nas mob ntshav qab zib, txo lub raum pathological puas tsuaj, txhim kho lub raum ua haujlwm, thiab ncua kev mob ntshav qab zib nephropathy.  

Kev Kho Mob Lupus Erythematosus (SLE)  

Inhibition of Autoantibody Production and Immune Complex Deposition: ARA-290 ho inhibits serum antinuclear antibody (ANA) thiab anti-ob-stranded DNA antibody qib nyob rau hauv induced SLE nas, txo IgG thiab C3 deposition nyob rau hauv lub raum, alleviates nephritis cov tsos mob, thiab txhim kho kab mob kev loj hlob ^[6].  

Daim duab 1 ARA290 kev kho mob suppressed inflammatory teb nyob rau hauv pristane-induced SLE nas. (A) Cov theem ntawm IL-6, IL-10, MCP-1, IFN-γ, TNF-α, IL-12p70 thiab TGF-β hauv cov ntshav tom qab kev kho mob tau piav qhia hauv daim duab 1 tau kuaj pom (n = 6). (B) Cov kab mob inflammatory macrophage F4/80 infiltration tau cuam tshuam los ntawm ARA 290 kev cuam tshuam piv rau PBS tswj. (C) Qhov hnyav ntawm tus po thiab lymph node tau ntsuas tom qab ARA290 kho hauv SLE nas (n = 6). Scale bars sawv cev rau 30 μm.

Source: PubMed ^[6]

Kev txo qis ntawm Cytokine Inflammatory Levels: ARA-290 txo cov ntshav cov ntshav ntawm cov kab mob inflammatory cytokines IL-6, MCP-1, thiab TNF-α hauv SLE nas, txo qhov mob thiab txo cov tsos mob ntawm tus kab mob ^[6].  

Txo Apoptosis: ARA-290 txo cov apoptotic hlwb hauv ob lub raum, tiv thaiv lub raum hlwb, thiab inhibits inflammatory activation ntawm macrophages thaum txhawb lawv phagocytosis ntawm apoptotic hlwb hauv vitro, tswj lub cev tiv thaiv kab mob thiab tuav lub peev xwm rau kev kho SLE ^[6].  

Mitigation of Chemotherapeutic Drug Toxicity  

Txo cov DNA puas: Hauv doxorubicin (DOX)-induced cytotoxicity qauv, ARA-290 ho txo ​​DOX-induced DNA puas, xws li txo tus Tsov tus tw DNA feem pua ​​​​ntawm comet assays thiab micronucleus zaus, tiv thaiv cellular genetic khoom thiab txo chemotherapeutic puas hlwb ^[7].  

Alleviation of Oxidative Stress and Inflammation: ARA-290 mitigates DOX-induced impairment of antioxidant enzyme act, txo o thiab apoptosis, thiab tiv thaiv DOX-induced oxidative kev nyuaj siab thiab cell puas, muaj feem xyuam nrog rau lub plawv hlwb, kom alleviate phiv nyob rau hauv cov neeg mob chemotherapy ^[7].  

Kev Tiv Thaiv thiab Kev Kho Mob Alzheimer's Disease  

Slowed Pathological Progression and Improved Cognition: Early Administration of ARA-290 in Young APP/PS1 nas (thaum ntxov Alzheimer's model) slows β-amyloid (Aβ) pathological progression thiab txhim kho kev txawj ntse, qhia txog nws qhov tseem ceeb rau kev cuam tshuam thaum ntxov ^[8].

Kev tswj hwm ntawm Monocyte Function: ARA-290 tshwj xeeb txhawb kev tsim ntawm Ly6C⁻ patrolling monocyte subsets, nce lawv cov qib, txhawb nqa Aβ tshem tawm ntawm cov hlab ntsha hauv hlwb, txo lub hlwb Aβ lub nra, thiab ncua kev kis kab mob. Txawm li cas los xij, nws tsis tshua muaj txiaj ntsig hauv cov qauv lig (hnub nyoog APP / PS1 nas), qhia txog qhov tseem ceeb ntawm kev cuam tshuam thaum ntxov ^[8].  

Txhawb Kev Mob Ntshav Qab Zib Kho Mob

Accelerated Wound Kaw: Hauv streptozotocin-induced mob ntshav qab zib incisional mob nas qauv, daim ntawv thov hauv zos ARA-290 ua rau kom lub qhov txhab kaw, ua kom lub sijhawm reepithelialization, thiab txhim kho qhov txhab zoo ^[9] .  

Kev tswj cov ntaub so ntswg kho cov cim: ARA-290 nce collagen thiab protein cov ntsiab lus hauv kev kho cov ntaub so ntswg, tswj cov tshuaj insulin, ntshav qabzib, qib lipid, tshuaj tiv thaiv kab mob, thiab qib cytokine pro-inflammatory, tsim kom muaj microenvironment conducive rau lub qhov txhab kho thiab muab tswv yim tshiab rau kev kho mob ntshav qab zib ko taw rwj ^[9].  

Pain Relief  

Inhibition of TRPV1 Channel Activity: ARA-290 relieves capsaicin-induced mechanical allodynia los ntawm inhibiting transient receptor tej zaum vanilloid subtype 1 (TRPV1) channel kev ua, ncaj qha tsom mus rau peripheral nociceptors thiab muab cov hom phiaj kho tshiab thiab cov hauv kev rau kev kho mob ^[4].  

Xaus  

ARA-290 yog ib qho EPO-derived polypeptide nrog kev tiv thaiv kab mob, tiv thaiv apoptotic, thiab tiv thaiv oxidative teebmeem. Nws tuaj yeem kho qhov mob hauv ntshav qab zib thiab sarcoidosis, txhawb cov paj hlwb rov tsim dua tshiab, tiv thaiv nephrotoxicity, SLE, kev nyuaj siab, thiab txo qhov mob los ntawm kev tawm tsam TRPV1. Nrog muaj peev xwm nyob rau hauv thaum ntxov Alzheimer's kev cuam tshuam thiab lwm yam kev lag luam, nws tuav cov ntawv thov kev kho mob dav dav.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Al-Onaizi, Mohammed yog ib tug kws tshawb fawb nrog kev txawj ntse hauv kev kho mob biomedicine. Nws muaj kev sib raug zoo nrog ntau lub tsev kawm ntawv thiab tshawb fawb, suav nrog Dasman Diabetes Institute (DDI), Kuwait University, Laval University, Western University (University of Western Ontario), thiab Hebrew University of Jerusalem. Nws cov kev xav tau tshawb fawb yog dav, suav nrog Neurosciences & Neurology, Biochemistry & Molecular Biology, Immunology, Psychiatry, thiab lwm yam ntsiab lus hauv Life Sciences & Biomedicine. Cov kev qhuab qhia no yog qhov tseem ceeb rau kev nkag siab tob txog tib neeg lub cev lub cev cov txheej txheem, txheej txheem kab mob, thiab kev tsim kho tshiab. Al-Onaizi, Mohammed txoj kev tshawb fawb tau ua tiav cov txiaj ntsig tseem ceeb hauv cov kev tshawb fawb yooj yim thiab tau muab qhov tseem ceeb theoretical kev txhawb nqa thiab kev taw qhia tswv yim rau kev kho mob thiab kev tshawb fawb biomedical.

▎ Cov Lus Qhia Tseem Ceeb

[1] Dahan A, Brines M, Niesters M, et al. Targeting lub innate kho receptor los kho neuropathy [J]. Pain Reports, 2016,1(1):e566.DOI:10.1097/PR9.0000000000000566.

[2] Ghassemi-Barghi N, Ehsanfar Z, Mohammadrezakhani O, et al. Mechanistic Approach for Protective Effect of ARA290, Ib qho tshwj xeeb Ligand rau Erythropoietin / CD131 Heteroreceptor, tiv thaiv Cisplatin-Induced Nephrotoxicity, Kev Koom Tes ntawm Apoptosis thiab Inflammation Pathways [J]. Inflamation, 2023,46(1):342-358.DOI:10.1007/s10753-022-01737-7.

[3] Wang R, Yang Z, Huang Y, et al. Erythropoietin-derived peptide ARA290 kho cov ntaub so ntswg hlwb tiv thaiv los ntawm $eta$-hom receptor nyob rau hauv nas nrog cerebral ischemic stroke[J]. CNS Neuroscience & Therapeutics, 2024, 30. https://api.semanticscholar.org/CorpusID:268414491.

[4] Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological mob los ntawm lub hom phiaj TRPV1 channel: Kev koom ua ke ntawm lub cev tiv thaiv kab mob thiab nociception [J]. Peptides, 2016,76:73-79.DOI:10.1016/j.peptides.2016.01.003.

[5] Xu G, Zou T, Deng L, et al. Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-zoo li tus cwj pwm thiab mob hauv nas[J]. Frontiers hauv Pharmacology, 2022, 13: 896601.

DOI: 10.3389/fpha.2022.896601.

[6] Huang B, Jiang J, Luo B, et al. Non-erythropoietic erythropoietin-derived peptide tiv thaiv nas los ntawm kab mob lupus erythematosus [J]. Phau ntawv Journal of Cellular and Molecular Medicine, 2018,22(7):3330-3339.DOI:10.1111/jcmm.13608.

[7] Shokrzadeh M, Etebari M, Ghassemi-Barghi N. Ib tug engineered non-erythropoietic erythropoietin-derived peptide, ARA290, attenuates doxorubicin induced genotoxicity thiab oxidative stress[J]. Toxicology hauv Vitro, 2020, 66: 104864.

DOI: 10.1016/j.tiv.2020.104864.

[8] Al-Onaizi MA, Thériault P, Lecordier S, et al. Thaum ntxov monocyte modulation los ntawm non-erythropoietic peptide ARA 290 decelerates AD-zoo li pathology kev loj hlob [J]. Brain Behavior and Immunity, 2022,99:363-382.

DOI: 10.1016/j.bbi.2021.07.016.

[9] Mashreghi M, Bayrami Z, Sichani N, et al. Ib qho kev tshawb nrhiav hauv vivo ntawm lub qhov txhab-kho kev ua haujlwm ntawm Specific ligand rau qhov kho qhov muag hauv lub cev, ARA290, siv tus qauv tsiaj mob ntshav qab zib [M]. 2023.DOI:10.21203/rs.3.rs-2520194/v1.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.