Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm elamipretide peptide hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo elamipretide peptide muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Elamipretide peptide(yav tas los hu ua SS{11}}31, MTP-131, Bendavia) yog ib qho khoom siv hluavtaws tetrapeptide compound, hmoov dawb, nrog rau cov tshuaj formula C32H49N9O5, CAS 736992-21-5, thiab ib qho hnyav ntawm 6.3 g. Muaj dej solubility zoo (50 mg / mL), ua kom yooj yim los npaj cov tshuaj txhaj tshuaj. Cov molecule no yog tsim los ntawm plaub cov amino acids, nrog cov kab ke D-Arg-Dmt-Lys-Phe-NH ₂ (Dmt yog 2,6-dimethyltyrosine). Nws cov qauv tshuaj tshwj xeeb endows nws nrog kev ua haujlwm lom neeg ntawm kev tsom mus rau mitochondria, nkag mus rau cov cell membranes, thiab stabilizing mitochondrial puab daim nyias nyias.
Peb cov khoom
| Khoom npe | Kev txhaj tshuaj Elamipretide | Elamipretide hmoov |
| Yam khoom | Txhaj tshuaj | Hmoov |
| Khoom Purity | Ntau dua lossis sib npaug li 99% | Ntau dua lossis sib npaug li 99% |
| Daim ntawv khoom | Rau kev siv sab nraud | Rau kev siv sab nraud |
Elamipretide COA
Molecular structural yam ntxwv
1. Amino acid muaj pes tsawg leeg thiab stereoconfiguration
Cov kab ke ntawmelamipretide peptide cov khoom lag luammuaj D-hom amino acids (D-Arg thiab Dmt), uas yog ib qho kev teeb tsa uas tsis yog ntuj tsim uas ua rau nws tiv taus protease degradation, ua kom ruaj khov hauv vivo. Kev hloov pauv ntawm cov amino acids uas muaj ntxhiab (Dmt thiab Phe) thiab cov amino acids yooj yim (D-Arg thiab Lys) tsim cov cation aromatic motifs, pab txhawb lawv txoj kev muaj peev xwm khi rau mitochondrial endomembrane cardiolipin.
2. Cardiolipin hom phiaj
Phospholipids yog cov yam ntxwv phospholipids ntawm mitochndrial puab daim nyias nyias, uas yog ib qho tseem ceeb rau kev tswj mitochndrial qauv (xws li cristae morphology) thiab electron hloov saw hlau (ETC) muaj nuj nqi. Elamipretid ntxig ib lub nplhaib hydrophobic aromatic rau hauv phospholipid bilayer los tsim ib qho chaw ruaj khov, yog li:
Tiv thaiv cardiolipin los ntawm everting mus rau sab nrauv ntawm mitochondria, inhibit cytochrome c tso thiab cascade cov tshuaj tiv thaiv ntawm apoptosis;
Tuav qhov kev txiav txim siab heev ntawm cristae thiab ua rau muaj kev cuam tshuam ntawm ATP synthase cov chaw nquag.
3. Charge tis thiab membrane permeability
Lub molecular nto yog tus nqi zoo (XLogP3 AA tus nqi yog 0) thiab khi rau lub taub hau cardiolipin tsis zoo los ntawm kev sib cuam tshuam electrostatic. Cov yam ntxwv no ua rau nws nkag mus rau hauv cov cell membrane sai sai thiab sib sau ua ke hauv mitochndrial membrane li ntawm 10 feeb, nrog rau ntau tshaj 1000 npaug ntawm cov cytoplasm.
Mitochondria ua lub luag haujlwm tseem ceeb hauv cellular metabolism, lub zog tsim, kev loj hlob thiab kev sib txawv, kev hloov pauv, thiab apoptosis. Cov kab mob Mitochndrial muaj kev kho mob heterogeneity thiab tuaj yeem cuam tshuam ntau yam kabmob thiab cov ntaub so ntswg. Cov tswv yim kho mob ib leeg ib leeg yog qhov nyuaj rau kev rov ua haujlwm mitochndrial. Muab tso rau hauv daim nyias nyias ntawm mitochondria thiab khi rau lub plawv phospholipids, nws txhim kho kev sib dhos ntawm ETS complexes rau hauv cov pa hypercomplex, txhim khu kev ua pa, txhim kho bioenergetics, txo ROS tiam, thiab txhim kho mitochndrial morphology. Nws kuj cuam tshuam nrog cov proteins uas cuam tshuam nrog mitochndrial inner membrane, tswj cov khoom electrostatic ntawm mitochndrial membrane nto, thiab txhim kho mitochndrial muaj nuj nqi los ntawm ntau qib.
Yav tag los,elamipretide peptide cov khoom lag luamtau ntseeg tias mitochndrial tiv thaiv cov nyhuv ntawm liraglutide tsuas yog los ntawm kev txo cov tiam ntawm reactive oxygen hom (ROS) thiab alleviating oxidative kev nyuaj siab. Txawm li cas los xij, cov kev tshawb fawb tom ntej tau pom tias nws tsis ua los ntawm "kev tshem tawm" ROS, tab sis txhim kho mitochndrial muaj nuj nqi ntawm ROS tiam thaum tswj mitochndrial inner membrane muaj peev xwm.
Nyob rau hauv xyoo tas los no, kev tshawb fawb tau pom tias liraglutide tsom rau mitochndrial inner membrane los ntawm kev cuam tshuam nrog plawv phospholipids. Cardiolipin yog ib qho anionic phospholipid uas ua lub luag haujlwm tseem ceeb hauv mitochndrial bioenergetics, suav nrog lub zog metabolism, cell apoptosis, teeb liab transduction, membrane stability thiab kinetics, nrog rau fission / fusion kinetics.
Nuclear magnetic resonance (NMR) cov kev tshawb fawb tau pom tias liraglutide khi rau hauv daim nyias nyias ntawm mitochondria, lipid vesicles ua raws li daim nyias nyias, thiab cais mitochondria, thiab qhov kev khi no nyob ntawm qhov muaj cardiolipin. Nws txoj kev khi rau cardiolipin yog cuam tshuam los ntawm CL acyl saw thiab tswj cov nqi ntawm mitochondrial membranes uas muaj cardiolipin. Kev tshawb fawb tau pom tias muaj ob lub xeev ntawm kev sib cuam tshuam ntawm liraglutide thiab daim nyias nyias: "peptide sib thooj" thiab "peptide embedding". Los ntawm tsis yog - tshwj xeeb ntxiv ntawm cov nqi ion zoo thiab cov tshuaj lom neeg sib cuam tshuam, qhov tsis zoo nqi ntawm daim nyias nyias bilayer nplua nuj hauv cardiolipin raug txo.
Kev khi ntawm liraglutide rau cardiolipin tuaj yeem cuam tshuam kev cuam tshuam ntawm cov protein thiab mitochndrial inner membrane, xws li txo cov oxidative hloov ntawm CL acyl chains los ntawm cytochrome c (CytC).
Nyob rau tib lub sijhawm, qhov kev sib khi no tseem hloov pauv lub cev lub cev ntawm daim nyias nyias, xws li nce kev sib koom ua ke ntawm tus kheej ntawm cardiophospholipids, txo qis qhov sib txawv ntawm lipids, txhim kho lateral tsub zuj zuj yam tsis muaj kev puas tsuaj rau cov txheej txheem bilayer, uas tuaj yeem txhawb nqa kev ua haujlwm mitochndrial.
Raws li cov txiaj ntsig kev tshawb fawb, Mitchell et al. npaj peb cov qauv los piav qhia txog cov txheej txheem kho mob ntawm imatinib downregulating lub peev xwm ntawm anionic mitochndrial daim nyias nyias: ua ntej, hloov cov kev faib tawm ntawm divalent cations (xws li Ca2+) thiab cuam tshuam cov khoom ntawm bilayer membranes; Qhov thib ob yog los txo cov tshuaj lom ntawm cov alkaline proteins (xws li CytC) thiab cardiolipin nplua nuj daim nyias nyias, thiab zam lipid peroxidation; Qhov thib peb yog los hloov cov khoom ntawm lub cev ntawm phospholipid bilayer membrane los ntawm kev txhawb nqa lipid tsub zuj zuj thiab hauv zos curvature.
Kev nkag siab tshiab rau hauv kev sib cuam tshuam ntawm liraglutide thiab mitochondrial inner membrane proteins
Cov tshuaj lom neeg hla-txuas kev siv thev naus laus zis sib txuas tuaj yeem siv los txheeb xyuas kev sib cuam tshuam ntawm cov protein hauv cov cell nyob thiab cov kab mob sib cais. Kev tshawb fawb tau pom tias muaj 12 tus ntoo khaub lig- txuas cov proteins hauv mitochondria incubated nrog biotin sau npe Iramipide (b-ELAM), uas cuam tshuam ncaj qha nrog plawv phospholipids thiab feem ntau muab faib ua ob pawg: cov koom nrog hauv ATP tiam thiab 2-oxoglutarate metabolism. Qhov no zoo ib yam nrog lub peev xwm ntawm Iramipide los txhim kho mitochndrial bioenergetics.
Ilamiside cuam tshuam nrog cytochrome c oxidase (CIV) subunit NDUA4, uas tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev koom ua ke ntawm CIV rau hauv supercomplex. B-Kev kho ELAM tuaj yeem ua kom qhov siab tshaj plaws ntawm kev sib txuas ntawm lub plawv mitochondria thiab CIV ua pa hauv cov nas laus, thaum txo qis H2O2 ntau lawm.
Ilamiside kuj tseem cuam tshuam ncaj qha nrog adenosine diphosphate (ADP) / ATP transferase (ANT) 1, hla- txuas nrog matrix nto ntawm ANT1 los ntawm ob qho lysine residues. Qhov kev sib cuam tshuam no cuam tshuam nrog nce ADP rhiab heev, thauj ntawm ADP los ntawm ANT1, thiab txo cov pa tawm ntawm proton los ntawm ANT1, uas pab tswj cov mitochndrial membrane muaj peev xwm thiab rov ua haujlwm mitochndrial.
Ilamiside tuaj yeem txhim kho ATP ntau lawm thiab mitochndrial tsis kam mus rau cellular stress hauv lub cev. Nyob rau hauv ib qho randomized placebo- tswj kev sim hauv cov neeg laus noj qab haus huv, ib koob tshuaj Ilamiside tuaj yeem ua kom lub zog muaj peev xwm ntawm cov leeg pob txha mitochondria.
Kev sib cuam tshuam ntawm Supercomplex hauv Electronic Transfer Systems
Ilamiside tsis tsuas yog khi ncaj qha rau ANT1, tab sis kuj txhim kho cov haujlwm ntawm ETS supercomplex. Nyob rau hauv ib txwm mitochondria, ua pa complexes I-IV sib sau ua ke rau hauv supercomplexes thiab cuam tshuam nrog fatty acid oxidase. Hauv cov kab mob mitochndrial xws li Barth syndrome, cov supercomplexes tsis ruaj khov thiab lawv cov lej txo. Kev sib txuas ntawm liraglutide txhawb kev sib dhos ntawm cov pa ua pa hypercomplex, txhim kho kev hloov hluav taws xob, txhim kho mitochndrial muaj nuj nqi, reshapes mitochondria, thiab txhawb kev tsim cov ntaub so ntswg.Elamipretide peptideKuj tseem tuaj yeem ua kom ruaj khov ATP synthesizers, suav nrog ANT, ATP synthase, creatine kinase, thiab inorganic phosphate carriers.
Nyob rau hauv nas plawv ischemia- qauv reperfusion, liraglutide tuaj yeem txhim kho hypercomplex coupling, txo cov fragmentation ntawm cristae network, thiab txhim kho cov qauv thiab kev ua haujlwm ntawm mitochondria.
Hauv TAFAZZIN gene knockout nas qauv ntawm Barth syndrome (BTHS), liraglutide tuaj yeem txhim kho mitochndrial ua pa muaj peev xwm thiab txhawb nqa lub koom haum ntawm hypercomplex. Hauv kev tshawb fawb vitro ntawm tib neeg lub plawv tsis ua haujlwm, liraglutide tuaj yeem txhim kho qhov sib txuas thiab oxygen flux ntawm supercomplex ntsig txog enzyme complexes I, III, thiab IV. Kev siv imatinib mus sij hawm ntev kuj tseem tuaj yeem kho cov synthesis li qub thiab kho cov hlab plawv phospholipids hauv cov neeg mob plawv tsis ua hauj lwm, thiab tswj qhov tsis txaus ntawm fusion thiab fission proteins.
Kev sib tham nrog Prohibitin
Hauv cov nas laus, imatinib cuam tshuam nrog txwv 2 txhawm rau txhim kho mitochndrial turnover thiab neuronal puas los ntawm inhibiting cGAS STING txoj kev thiab M1 microglial polarization. Knocking down txwv 2 yuav tshem tawm cov kev tiv thaiv ntawm liraglutide.
Lub luag hauj lwm ntawm lub hom phiaj centripetal phospholipid enrichment cheeb tsam nyob rau hauv kev kho mob ntawm mitochondrial dysfunction kab mob
Cov teebmeem ntawm liraglutide ntawm cov qauv mitochndrial, dynamics, thiab kev ua haujlwm ua rau nws ua lub luag haujlwm zoo hauv cov qauv ua ntej ntawm ntau yam mitochndrial tsis ua haujlwm. Txawm li cas los xij, vim nws txoj kev xaiv khi rau cardiolipin, nws tsuas yog siv tau rau cov kab mob mitochndrial nrog cardiolipin txawv txav.
4.1. Cardiac dysfunction model
Cov yam ntxwv ntawm cardiomyopathy thiab lub plawv tsis ua hauj lwm suav nrog kev tsim tsis ruaj khov ntawm ETS hypercomplex, kev hloov pauv hauv mitochndrial dynamics thiab ultrastructure, txo ATP synthesis, ntau dhau ROS tiam, thiab dissociation ntawm fatty acid oxidase. Hauv fibroblasts ntawm cov neeg mob dilated cardiomyopathy nrog ataxia syndrome (DCMA), liraglutide tuaj yeem thim rov qab mitochndrial fragmentation thiab ntau dhau ROS tiam, nce qib ntawm daim ntawv ntev ntawm mitochndrial crest remodeling protein optic atrophy 1 (Opa1), thiab tswj mitochndrial membrane ultrastructure.
Nyob rau hauv cov laus nas qauv ntawm sab laug ventricular diastolic tsis ua hauj lwm, kev kho mob nrog liraglutide rau 8 lub lis piam tuaj yeem normalize sab laug ventricular diastolic muaj nuj nqi, txhim kho kev tawm dag zog, txo qis plawv hypertrophy, thiab kho mitochndrial proton to thiab ROS tsim kom zoo. Hauv tus qauv nas ntawm cov neeg laus systolic dysfunction, imatinib tuaj yeem rov qab muaj hnub nyoog - ntsig txog sab laug ventricular dysfunction.
Hauv cov qauv npua ntawm hypercholesterolemia ua rau lub raum vascular hypertension, imatinib tuaj yeem txhim kho sab laug ventricular diastolic muaj nuj nqi, txo qis plawv hypertrophy, thiab tsis cuam tshuam rau ntshav siab thiab kev ua haujlwm systolic. Hauv tus qauv canine plawv tsis ua hauj lwm, ntev- siv liraglutide tuaj yeem txhim kho sab laug ventricular contraction thiab mitochndrial muaj nuj nqi, txo N-terminal pro hlwb natriuretic peptide (NT proBNP) thiab pro- inflammatory cytokine theem.
Hauv cov qauv mob plawv ntev dhau los, imatinib tuaj yeem tiv thaiv kev ntxhov siab -induced necrosis thiab apoptosis, thiab tiv thaiv kev tuag ntxov ntawm cov tsiaj.
Hauv hypertrophic cardiomyopathy (HCM), imatinib tuaj yeem tiv thaiv ROS induced bradycardia ntawm ventricular conduction, yog li tiv thaiv arrhythmia.
Skeletal leeg tsis ua haujlwm qauv:
Hauv cov qauv tshuaj ntsuam xyuas hnub nyoog - cuam tshuam txog mitochondrial tsis ua haujlwm hauv cov leeg pob txha, imatinib tuaj yeem txhim kho cov leeg pob txha, suav nrog kev ua kom lub zog metabolism, txhim kho kev qaug zog, thiab ua kom muaj zog ua haujlwm. Hauv cov neeg laus, ib koob tshuaj liraglutide tuaj yeem ua rau ATPmax ntawm cov leeg pob txha thiab txhim kho cov leeg nqaij qaug zog. Nyob rau hauv tus qauv mob plawv tsis ua hauj lwm dog dig, ntev - kev kho mob ntev nrog liraglutide tuaj yeem kho cov leeg nqaij fiber ntau hom thiab txhim kho kev tawm dag zog. Cov kev sim hauv vitro tau pom tias liraglutide tuaj yeem siv tshuaj raws li kev txhim kho lossis rov ua haujlwm ntawm mitochndrial cov cim qhia hauv cov leeg pob txha.
Hnub nyoog ntsig txog macular degeneration qauv
Kev poob qis hauv mitochondrial muaj nuj nqi cuam tshuam nrog kev hloov pauv hauv cov xim ntawm lub paj hlwb epithelial (RPE) hauv lub hnub nyoog - ntsig txog macular degeneration (AMD). Hauv cov qauv nas ntawm qhov muag pom kev laus, imatinib muaj kev tiv thaiv ntawm RPE thiab txhim kho qhov pom kev ua haujlwm. Hauv RPE cell kab lis kev cai ntawm AMD cov neeg mob, imatinib tuaj yeem txhim kho cell viability thiab mitochndrial muaj nuj nqi. Nyob rau hauv lub hnub nyoog - ntsig txog qhov pom kev tsis pom kev nas, imatinib tuaj yeem txo qhov pom kev tsis pom kev thiab rov ua kom pom qhov qub thiab qhov sib txawv ntawm qhov sib txawv hauv ob lub hlis.
Clinical kev nce qib ntawm imatinib
Cov txiaj ntsig zoo ntawm liraglutide ntawm cov qauv mitochndrial, kev ua kom muaj zog, thiab kev ua haujlwm tau ua rau muaj peev xwm kho tau cov teebmeem hauv kev sim tshuaj ntawm ntau yam kab mob mitochondrial, tab sis tag nrho cov kev soj ntsuam tau sib xyaw ua ke, qhia txog qhov nyuaj ntawm kev soj ntsuam mitochndrial tsom cov kev kho mob.
1. Kev kho mob ntawm Barth syndrome
Hauv 2/3 theem randomized ob - qhov muag tsis pom kev hla kev kuaj mob (TAZPOWER) tsom rau 12 tus neeg mob nrog Barth's syndrome, 12 lub lis piam ntawm kev kho mob imatinib tsis ua tiav qhov kawg ntawm kev txhim kho hauv 6-feeb taug kev sim (6MWT) thiab Barth's syndrome (10}SAUM){201} asessessment{101} Txawm li cas los xij, thaum lub sij hawm qhib daim ntawv lo, Iramipide tau pom muaj kev txhim kho tseem ceeb hauv 6MWT, BTHS-SA, thiab qee qhov kawg ntawm lub hauv caug xws li lub hauv caug extensor zog, tag nrho cov kev xav ntawm cov tsos mob los ntawm cov neeg mob, thiab qee qhov kev mob plawv.
Kev sib piv ntawm 8 cov neeg mob uas ua tiav yam tsawg kawg 72 lub lis piam ntawm lub sijhawm qhib daim ntawv lo thiab tsis kho cov neeg mob keeb kwm yav dhau los tau pom tias ntev - siv imatinib tuaj yeem txo qis hauv kev ua haujlwm ntawm lub plawv thiab txhim kho lub peev xwm ua haujlwm.
2. Kev sim tshuaj ntawm lub hnub nyoog - ntsig txog macular degeneration
Hauv theem 2 randomized placebo-tswj ob npaug- qhov muag tsis pom kev sim (ReCLAIM-2) tsom rau AMD cov neeg mob hnub nyoog 55 xyoo lossis tshaj saud uas tsis yog lub hauv paus geographic atrophy (GA), kev kho mob nrog imatinib tsis ua tiav qhov kawg ntawm qhov kawg (qhov nruab nrab hloov pauv hauv qhov tsis tshua muaj qhov ci zoo tshaj plaws kho qhov muag pom kev acuity 10} square, tab sis qhov nruab nrab ntawm BC hloov dua siab tshiab {{ GA 10}) txo qhov nruab nrab ntawm kev loj hlob ntawm macular tag nrho ellipsoid (EZ) attenuation los ntawm 43% thiab qhov nruab nrab kev loj hlob ntawm ib nrab EZ attenuation los ntawm 47%. Kev soj ntsuam Post hoc tau pom tias liraglutide tau ua haujlwm tau zoo hauv kev txo qis kev loj hlob ntawm ib nrab thiab tag nrho EZ attenuation, thiab ntau tus neeg mob tau pom ntau dua lossis sib npaug rau 2 kab ntawm kev txhim kho hauv LL-BCVA. Kev hloov pauv hauv LL-BCVA tau cuam tshuam nrog kev hloov pauv hauv tag nrho macular EZ attenuation.
3. Kev sim tshuaj ntawm thawj mitochondrial myopathy
MMPOWER-3 yog ib qho randomized, ob npaug - dig muag, cov tshuaj placebo tswj kev sim tsom rau 218 tus neeg mob nrog thawj mitochndrial myopathy. Primary mitochndrial myopathy yog ib pawg kab mob caj ces uas feem ntau cuam tshuam rau cov leeg pob txha.Elamipretide peptidemuaj tag nrho cov kam rau ua zoo, thiab feem ntau cov kev phiv tshwm sim yog me me mus rau nruab nrab qhov chaw txhaj tshuaj. Nyob rau hauv lub hom phiaj los kho cov pej xeem, imatinib tsis tau mus txog qhov kawg ntawm qhov kawg (hloov hauv 6MWT thiab tag nrho cov qhab nia qaug zog ntawm thawj mitochndrial myopathy symptom ntsuam xyuas [PMMSA]), tab sis gene subgroup tsom xam pom tias cov neeg mob nqa cov kev hloov pauv hauv DNA (tsis yog mitochndrial DNA hloov pauv) pom tau tias muaj kev txhim kho tseem ceeb hauv cov kev kho mob ntawm imatinib pab pawg 6W. ntawm kev txiav txim siab gene subtypes thaum ntsuas mitochndrial targeted therapy.
FAQ
- Puas yog Elamipretide raug cai?
FDA nyuam qhuav pom zoo Elamipretide: Qhov ntawd txhais tau li cas rau kev lag luam zoo nkauj thiab kev noj qab haus huv. Nyob rau hauv ib qho kev txav uas muaj ntau yam nyob rau hauv lub neej ntev thiab kev noj qab haus huv qhov chaw buzzing, FDA tsis ntev los no tau pom zoo Elamipretide rau kev kho mob ntawm Barth syndrome, ib tug tsis tshua muaj mitochondrial teeb meem.
- Elamipretide puas tuaj yeem thim rov qab kev laus?
Elamipretide thim rov qab hnub nyoog- cuam tshuam txog kev poob qis hauv qhov siab tshaj plaws mitochondrial ATP ntau lawm (ATPmax) thiab kev sib txuas ntawm oxidative phosphorylation (P / O).
- Nws siv sijhawm ntev npaum li cas Elamipretide ua haujlwm?
Elamipretide pib ua haujlwm sai, nrog kev txhim kho lub zog pom nyob rau hauv 1-2 lub lis piam, tab sis cov txiaj ntsig tseem ceeb feem ntau siv 2-4 lub lis piam lossis ntev dua, nyob ntawm qhov xwm txheej, nrog rau lub sij hawm ntev xws li txo qhov mob lossis txhim kho lub plawv ua haujlwm tshwm sim tom qab lub lis piam lossis ntau lub hlis ntawm kev siv zoo ib yam, vim nws ua haujlwm los kho mitochondrial muaj nuj nqi.
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