BAM 15 peptideyog ib qho me me molecule mitochondrial proton uncoupling tus neeg sawv cev nrog cov qauv tshuaj tshwj xeeb. Nws lub npe tshuaj yog N5, N6 bis (2- fluorophenyl) - [1,2,5] oxadiazolo [3,4-b] pyrazine-5,6-diamine, nrog rau cov mis mos ntawm C16H10F2N6O thiab molecular hnyav rau 340.29 daltons Cov molecule tsim ib tug peb-dimensional conformation nrog proton carrier kev ua si los ntawm ib tug tshwj xeeb kev npaj ntawm fluorophenyl thiab oxadiazole pyrazine skeleton. Nws Canonical SMILES structural formula FC (C=CC=C1)=C1NC2=NC3=NON=C3N=C2NC4=C (C=}C1NC{25}}NC3=NON=C3N=C2NC4=C (C=C4) ntawm kev faib tawm Fug} thiab hydrogen daim ntawv cog lus pub / txais, uas ua rau nws tshwj xeeb khi rau proton gradient ntawm mitochondrial puab daim nyias nyias thiab tswj lub zog metabolism los ntawm uncoupling oxidative phosphorylation txheej txheem.
Hais txog lub cev thiab tshuaj lom neeg, BAM15 nthuav tawm cov kuab tshuaj tseem ceeb nyob ntawm kev solubility. Kev sim cov ntaub ntawv qhia tau hais tias cov solubility ntawm cov molecule nyob rau hauv dimethyl sulfoxide (DMSO) tuaj yeem ncav cuag 75 mg / mL (220.40 mM), thaum nws solubility hauv dej yog qis dua 0.1 mg / mL, qhia txog lub xeev insoluble tag nrho. Cov yam ntxwv no yuav tsum muaj kev txhim kho ntawm nws cov qauv siv DMSO ua cov kuab tshuaj tseem ceeb thiab ua ke nrog kev kho ultrasonic (ultrasonic oscillation nyob rau hauv 37℃dej da dej tej yam kev mob) los txhim kho kev ua kom tiav. Nws cov xwm txheej khaws cia yog nruj me ntsis txwv rau -20℃thiab cia tsaus. Hauv daim ntawv hmoov, nws tuaj yeem ruaj khov khaws cia rau 3 xyoos, thaum nyob rau hauv daim ntawv daws teeb meem, nws tuaj yeem tswj kev ua haujlwm rau 6 lub hlis ntawm -80 degree.
Peb cov khoom
Ceftiofur +. COA
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Certificate of Analysis |
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Compound npe |
BAM-15 | |
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CAS Nr. |
210302-17-3 | |
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Qib |
Pharmaceutical qib | |
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Ntau |
Customized | |
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Ntim txheem |
Customized | |
| Chaw tsim tshuaj paus | Shaanxi BLOOM TECH Co., Ltd | |
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Ntau No. |
20250109001 |
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MFG |
Jan 12th 2025 |
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EXP |
Jan 8th 2029 |
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Qauv |
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| TEST STANDARD | GB/T24768-2009 Kev lag luam. Stnndard | |
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Yam khoom |
Enterprise txheem |
Kev txheeb xyuas qhov tshwm sim |
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Qhov tshwm sim |
Dawb los yog yuav luag dawb hmoov |
Ua raws |
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Cov ntsiab lus dej |
Tsawg dua lossis sib npaug li 4.5% |
0.30% |
| Poob rau ziab |
Tsawg dua lossis sib npaug li 1.0% |
0.15% |
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Hnyav Hlau |
Pb Tsawg dua lossis sib npaug li 0.5ppm |
N.D. |
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Tsawg dua lossis sib npaug li 0.5ppm |
N.D. | |
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Hg Tsawg dua lossis sib npaug li 0.5ppm |
N.D. | |
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Cd Tsawg dua lossis sib npaug li 0.5ppm |
N.D. | |
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Purity (HPLC) |
Ntau dua lossis sib npaug li 99.0% |
99.5% |
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Ib qho impurity |
<0.8% |
0.48% |
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Residue ntawm ignition |
<0.20% |
0.064% |
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Tag nrho microbial suav |
Tsawg dua lossis sib npaug li 750cfu / g |
80 |
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E. Coli |
Tsawg dua lossis sib npaug li 2MPN / g |
N.D. |
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Salmonella |
N.D. | N.D. |
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Ethanol (los ntawm GC) |
Tsawg dua lossis sib npaug li 5000ppm |
400ppm ua |
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Cia |
Khaws rau hauv qhov chaw kaw, tsaus thiab qhuav ntawm -20 degrees |
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Mechanism ntawm kev txiav txim thiab kev tswj cov metabolism
Lub ntsiab mechanism ntawmBAM 15 peptidenyob rau hauv nws lub luag hauj lwm raws li ib tug proton carrier, uas lov lub coupling kev sib raug zoo ntawm proton kinetic muaj peev xwm (PMF) thiab ATP synthesis los ntawm kev tsim proton raws nyob rau hauv lub puab membrane ntawm mitochondria. Cov kev sim hauv vitro tau pom tias qhov ib nrab ua tau zoo concentration (EC50) ntawm cov molecule nyob rau hauv L6 myoblasts yog 270 nM, thiab nws lub zog ntawm kev txiav txim yog piv rau classical uncoupling tus neeg saib xyuas FCCP, tab sis nrog lub wider concentration teb qhov rais. Nyob rau hauv cov koob tshuaj ntawm 100 nM mus rau 1 μ M, BAM15 tuaj yeem ua rau nce cellular oxygen noj tus nqi (OCR) mus rau FCCP qib; Nyob rau hauv lub siab concentration ntau ntawm 1 μ M mus rau 50 μ M, nws muaj peev xwm tswj tau uncoupling ua pa yog ho zoo dua FCCP, thiab nws tsis ua rau ib tug nce nyob rau hauv reactive oxygen hom (ROS) ntau ntau. Cov yam ntxwv no tshwm sim los ntawm nws qhov tshwj xeeb proton conduction efficiency thiab daim nyias nyias muaj peev xwm tswj tau, tso cai rau BAM15 kom nce basal metabolic tus nqi thaum tsis txhob oxidative kev nyuaj siab puas tsuaj los ntawm ib txwm uncoupling agents xws li DNP.
2. Reshaping ntawm lub zog metabolism
Cov kev sim tsiaj tau pom tias BAM15 tuaj yeem tswj hwm lub zog sib npaug los ntawm ntau txoj hauv kev. Hauv kev noj zaub mov kom rog rog (DIO) tus qauv nas, kev cuam tshuam 8-lub lim tiam ua rau 35% txo qis hauv lub cev rog cov ntsiab lus, thaum lub cev hnyav (LBM) nyob ruaj khov. Cov txheej txheem metabolic muaj xws li:
Hloov hauv substrate oxidation nyiam: txhawb kev fatty acid oxidation (FAO) txoj kev, inhibits glycolysis pyruvate dehydrogenase complex (PDH) kev ua, thiab hloov lub zog los ntawm carbohydrates rau lipids;
Kev txhim kho Mitochondrial biogenesis: induces cov kev qhia ntawm peroxisome proliferator activated receptor gamma co activator 1 alpha (PGC-1 alpha), txhim kho mitochondrial DNA daim qauv thiab ua pa saw complex kev ua si;
Brown adipose zoo li phenotype activation: induces uncoupling protein 1 (UCP1) qhia nyob rau hauv dawb adipose ntaub so ntswg (WAT), txhawb upregulation ntawm thermogenic noob cov kev pab cuam xws li PPAR thiab CPT1.
Kev tswj hwm cov txiaj ntsig ntawm BAM15 ntawm cov piam thaj metabolism yog cuam tshuam los ntawm kev kho cov kab mob insulin. Hauv db / db cov nas ntshav qab zib mellitus, kev tswj hwm tas li rau 4 lub lis piam txo cov ntshav qabzib yoo mov los ntawm 42%, qib insulin los ntawm 30%, thiab txhim kho thaj chaw zoo nyob rau hauv kev kuaj ntshav qabzib (IPGTT) nkhaus (AUC). Kev tshawb fawb Mechanism qhia tias nws txhim kho cov tshuaj insulin los ntawm cov hauv qab no:
Skeletal leeg qabzib uptake: activates AMPK-AS160-GLUT4 txoj hauv kev, txhawb cov membrane GLUT4 translocation;
Inhibition ntawm hepatic gluconeogenesis: downregulation ntawm phosphoenolpyruvate carboxykinase (PEPCK) thiab qabzib-6-phosphatase (G6Pase) qhia;
Inflammatory cytokine regulation: Inhibits macrophage M1 polarization thiab txo qhov tso tawm ntawm pro-inflammatory cytokines xws li TNF - thiab IL-6.
Kev nce qib hauv kev tshawb fawb preclinical thiab ntau yam kev tiv thaiv kab mob
1. Kev rog rog thiab metabolic syndrome cuam tshuam
Hauv DIO tus qauv nas,BAM 15 peptidenthuav tawm cov yam ntxwv kho mob zoo dua piv rau cov tshuaj ib txwm:
Kev tswj qhov hnyav: Ntawm qhov koob tshuaj ntawm 0.1 mg / kg / d, kev cuam tshuam 12 lub lis piam ua rau qhov hnyav nce ntxiv ntawm 58%, tsis muaj kev tshaib plab lossis kub hloov pauv;
Fatty daim siab thim rov qab: txo daim siab triglyceride cov ntsiab lus los ntawm 67%, txo cov hepatocyte ballooning thiab inflammatory infiltration;
Lipid profile optimization: txo cov ntshav qabzib tsawg- ntom lipoprotein cholesterol (LDL-C) thiab cov rog dawb (FFA) qib, thaum nce siab -cov roj lipoprotein ceev (HDL-C) cov ntsiab lus.
2. Lub raum tiv thaiv nyhuv
Cov kev tshawb fawb txog kev raug mob raum mob (AKI) cov qauv tau pom tias BAM15 pretreatment tuaj yeem txo cov ischemia zoo heev-reperfusion (I/R) raug mob:
Lub raum ua haujlwm ntsuas: plasma creatinine (Cr) thiab urea nitrogen (BUN) qib txo qis los ntawm 52% thiab 41%, feem;
Kev txhim kho histopathological: txo thaj tsam ntawm lub raum tubular necrosis los ntawm 63%, inhibited qhov txhuam ntawm cov npoo ntawm cov tubules thiab lub cev tiv thaiv kab mob;
Kev tshawb nrhiav tshuab: Los ntawm kev ua kom txoj hauv kev mitochondrial STAT3, inhibiting NLRP3 inflammasome los ua ke, thiab txhawb nqa mitochondrial autophagy kom tshem tawm cov mitochondria puas.
3. Cov leeg ua haujlwm tu
Hauv cov qauv ntawm sarcopenia cuam tshuam nrog kev laus, BAM15 kev cuam tshuam tau pom los tiv thaiv atrophy:
Kev hloov pauv ntawm cov leeg nqaij fiber ntau: nce qhov feem ntawm hom II ceev cov nqaij fibers los ntawm 18% thiab txhim kho cov leeg nqaij;
Protein homeostasis regulation: inhibits cov kev ua ntawm ubiquitin proteasome system (UPS) kho los ntawm FoxO transcription yam thiab txo cov degradation ntawm myosin hnyav saw (MyHC);
Mitochondrial zoo tswj: txhawb mitochondrial fission fusion tshuav nyiaj li cas, txhim kho mitochondrial membrane peev xwm (Δ PSI m) thiab ua pa tswj tus nqi (RCR).
Kev cia siab rau kev tsim kho thiab kev txhais lus kho mob
Hais txog dej insolubility ntawm BAM15, kev tshawb fawb thiab kev loj hlob tam sim no yog tsom rau nano xa khoom siv tshuab:
Liposome encapsulation: Nanoliposomes npaj siv DSPC / cholesterol / DSPE-PEG2000 (molar ratio 55:40:5) tuaj yeem ua kom cov tshuaj encapsulation efficiency nce mus txog 92%, tswj cov particle loj ntawm 120 ± 15 nm, thiab ua kom ntev cov ntshav ncig lub sij hawm (t1/2); los ntawm 0 .
Polymer micelles: Lub micelle system tsim siv mPEG PLGA ua tus nqa khoom, nrog cov tshuaj tso tawm tsuas yog 18% nyob rau hauv pH 7.4 cov xwm txheej, thiab tso tawm tus nqi ntawm 76% tom qab 48 teev nyob rau hauv pH 6.5 cov xwm txheej simulated hauv qog microenvironment, ua tiav lub hom phiaj xa khoom.
Raws li cov ntaub ntawv tshawb fawb uas twb muaj lawm, txoj kev kho mob kev loj hlob ntawm BAM15 qhia tau hais tias muaj kev sib txawv:
Cov kab mob metabolic: raws li kev kho mob sib xyaw ua ke ntawm GLP-1 receptor agonists (xws li semaglutide), nws tawg los ntawm kev kho cov fwj tshuaj ntawm cov tshuaj poob phaus uas twb muaj lawm los ntawm kev sib koom ua ke tswj kev siv zog thiab kev siv nyiaj;
Kev laus cov kab mob: tshawb xyuas lub peev xwm ntawm mitochondrial dysfunction ntsig txog cov kab mob xws li sarcopenia thiab cov kab mob neurodegenerative li neuroprotective lossis cov leeg nqaij ua kom muaj zog;
Kev tiv thaiv lub cev: Hauv cov xwm txheej xws li kev phais plawv thiab kev hloov pauv hauv nruab nrog cev, nws ua haujlwm ua tus tiv thaiv kab mob perioperative mitochondrial kom txo qis ischemia- raug mob rov qab.
Kev txhais lus kho mob ntawm BAM15 yuav tsum tau kov yeej cov teeb meem hauv qab no:
Kev faib cov ntsiab lus: Raws li ib tug ciam teb tsis meej pem ntawm me me molecule compounds thiab peptide tshuaj, nws yuav cuam tshuam rau kev xaiv ntawm IND tshaj tawm txoj kev;
Kev loj hlob ntawm Biomarker: Nws yog ib qho tsim nyog los tsim kom muaj cov kev ua haujlwm ntawm mitochondrial (xws li OCR, ATP / ADP piv) raws li cov ntsiab lus ntawm cov tshuaj siv tshuaj los txhawb kev tshawb nrhiav tshuaj;
Kev txheeb xyuas kev nyab xeeb mus ntev: Kev tshawb fawb ntxiv uas suav nrog kev tsim cov tshuaj toxicity, caj ces toxicity, thiab lwm yam kev lag luam yuav tsum tau ua kom tau raws li kev cai tswj hwm ntawm FDA / EMA rau cov tshuaj metabolic.
BAM 15 peptide, raws li lub cim tshiab ntawm mitochondrial uncoupling tus neeg sawv cev, tau qhia dav dav hauv kev kho cov kab mob metabolic los ntawm nws cov qauv tshuaj tshwj xeeb thiab cov txheej txheem ntawm kev ua. Nws ntau- lub hom phiaj tswj kev muaj peev xwm tsis txwv rau lub zog metabolism, tab sis txuas mus rau cov txheej txheem pathological xws li o, oxidative stress, thiab protein homeostasis. Txawm hais tias kev hloov pauv hauv chaw kho mob tseem ntsib cov teeb meem xws li kev npaj ua kom zoo thiab ua pov thawj kev nyab xeeb, nrog rau kev ua tiav ntawm kev xa khoom thiab kev sib sib zog nqus ntawm kev tshawb nrhiav tshuaj kho mob, BAM15 yuav tsum dhau los ua cov tshuaj tseem ceeb rau kev hloov pauv ntawm kev kho cov kab mob metabolic, muab cov kev daws teeb meem tshiab rau kev rog rog, ntshav qab zib, NAFLD thiab lwm yam kab mob.
Kev nyab xeeb thiab kam rau ua
CovBAM 15 Peptide(BAM15) tau ua kom pom kev nyab xeeb zoo thiab ua siab ntev hauv kev sim tsiaj. Cov ncauj lus kom ntxaws yog raws li nram no:
Kev Nyab Xeeb Kev Nyab Xeeb hauv Tsiaj Kev sim
Tsawg cytotoxicity
Ntawm qhov siab txog li 50 μM, lub cell ciaj sia taus ntawm BAM15-kho cov hlwb tau nce siab dua li ntawm cov tshuaj uncoupling tus neeg sawv cev FCCP (raws li qhia hauv kev sim mitochondrial o, qhov feem pua ntawm cov cell tuag vim yog BAM15 qis dua).
Qhov kev sim ua kom pom tias BAM15 tau txhawb nqa cov pa oxygen noj (OCR) yam tsis muaj qhov ua kom cov pa oxygen reactive (ROS) qib, txo cov kev ntxhov siab oxidative.
Kev tiv thaiv lub cev
Kev tiv thaiv raum: Hauv lub raum mob ischemia- tus qauv raug mob rov ua dua, cov plasma creatinine qib ntawm cov nas uas kho nrog BAM15 txo qis, cov necrosis ntawm lub raum tubules tau txo, qhov cuam tshuam ntawm tubular obstruction tau txo, thiab kev nkag mus ntawm lub cev tiv thaiv kab mob tau txo.
Neuroprotection: Hauv iPS cov ntaub so ntswg sib txawv, BAM15 tuaj yeem ua rau tsis muaj zog apoptosis los ntawm kev thauj thiab txo cov kev pheej hmoo ntawm cov kab mob neurodegenerative.
Metabolic kev nyab xeeb
Tsis muaj qhov kub thiab txias: Tsis zoo li cov tshuaj tsis sib xws xws li DNP, BAM15 tsis ua rau muaj qhov txawv txav los yog txo qis hauv lub cev kub ntawm qhov koob tshuaj zoo.
Cov ntshav tsis nyob ib puag ncig: Kev tswj hwm lub sijhawm ntev tsis tau ua rau cov cim toxicity txawv txav xws li cov ntshav niaj hnub, lub siab thiab lub raum ua haujlwm.
Tolerability Zoo
Qhov ncauj bioavailability
Qhov ncauj bioavailability ntawm BAM15 mus txog 67%, feem ntau faib rau hauv daim siab, thiab tau maj mam tshem tawm ntawm cov ntaub so ntswg hauv 4 teev. Cov yam ntxwv pharmacokinetic tau ruaj khov.
Tom qab kev tswj hwm qhov ncauj, kev siv zog ntawm cov nas txuas ntxiv nce ntxiv (rau qhov koob tshuaj ntawm 100 mg / kg, OCR yog 48% siab dua li cov hauv paus ntsiab lus thiab maj mam rov qab mus rau qhov qub tom qab 3 teev), qhia tias muaj kev zam zoo.
Tsis qab los noj mov los yog nqaij poob
Hauv kev noj haus-mob rog rog, BAM15 (0.05%-0.15% w/w) tuaj yeem cuam tshuam tag nrho cov rog, tab sis tsis cuam tshuam rau kev noj zaub mov lossis cov leeg nqaij.
Tsis zoo li cov molecules xws li GDF15 uas txo qhov hnyav los ntawm inhibiting qab los noj mov, BAM15 ua ncaj qha los ntawm kev ua kom lub zog noj, tsis txhob muaj kev cuam tshuam hauv nruab nrab paj hlwb.
koob tshuaj -nyob ntawm cov nyhuv
Cov koob tshuaj tsawg (0.05% w/w) tuaj yeem tiv thaiv ntau dua 50% ntawm cov rog nce, koob tshuaj siab (0.10%-0.15% w/w) ua rau muaj kev cuam tshuam cov rog tag nrho, thiab tsis muaj kev txwv tshuaj toxicity tau pom.
Muaj peev xwm txaus ntshai thiab txwv
Luv ib nrab-lub neej
Hauv kev sim tsiaj, lub sijhawm ua haujlwm zoo ntawm BAM15 hauv lub cev raug txwv (xws li cov tshuaj siv tau ntev li ntawm 3-4 teev), thiab kev tswj xyuas ntau zaus lossis kev tsim kho kom zoo yuav tsum tau ua kom muaj txiaj ntsig zoo.
Tib neeg kev nyab xeeb tsis paub
Txawm hais tias tsis muaj kev cuam tshuam loj heev hauv cov tsiaj sim, tib neeg cov metabolism txawv ntawm cov tsiaj, thiab kev nyab xeeb yuav tsum tau kuaj xyuas los ntawm kev sim tshuaj (xws li cov teebmeem ntawm lub siab thiab lub plawv tom qab ntev - kev tswj hwm).
complex mechanism ntawm kev txiav txim
BAM15 ua los ntawm ntau txoj hauv kev xws li mitochondrial uncoupling thiab AMPK activation, thiab tej zaum yuav cuam tshuam nrog lwm yam tshuaj, xav tau kev tshawb fawb ntxiv.
FAQ
1. Lo lus nug: Dab tsi yog qhov txawv ntawm BAM 15 thiab classic mitochondrial uncoupling agents (xws li DNP)?
Teb: Lub hom phiaj xaiv. BAM 15 yog tsim los ua tus neeg nqa khoom proton, tab sis cov kev tshawb fawb tau pom tias nws muaj kev xaiv ntau dua rau cov mitochondrial membrane thiab tsis tshua muaj kev cuam tshuam rau daim nyias nyias. Qhov no txhais tau hais tias nws yuav muaj peev xwm ua kom muaj peev xwm txhawb kev tsim hluav taws xob yam tsis muaj kev cuam tshuam rau kev ua haujlwm ntawm lwm cov cellular organelles (xws li endoplasmic reticulum calcium homeostasis), aiming kom muaj lub qhov rais kho kom zoo dua thiab kev nyab xeeb hauv txoj kev xav.
2. Lo lus nug: Puas yog BAM 15 puas muaj kev cuam tshuam ncaj qha rau cov ntaub so ntswg adipose (BAT)?
Teb: Lub luag haujlwm tseem ceeb yog tsis ncaj qha qhib BAT. Cov txheej txheem tseem ceeb ntawm BAM 15 yog tshuaj uncoupling, uas cuam tshuam nrog "txo" protons thoob plaws hauv lub mitochondrial membrane, yog li dissipating zog nyob rau hauv daim ntawv ntawm tshav kub. Nws feem ntau ua haujlwm hauv cov ntaub so ntswg nrog cov oxidative metabolism hauv siab (xws li cov leeg pob txha, daim siab). Nws cov txiaj ntsig ntawm BAT kev ua haujlwm tuaj yeem ua tsis ncaj (xws li los ntawm kev hloov pauv hauv tag nrho lub zog metabolism), tsis yog ncaj qha rau BAT raws li qhov xwm txheej nrog 3-adrenergic receptor agonists.
3. Lo lus nug: Dab tsi yog qhov teeb meem loj tshaj plaws tam sim no tiv thaiv daim ntawv thov kev kho mob ntawm BAM 15?
Teb: koob tshuaj -nyob ntawm kev pheej hmoo ntawm hyperthermia. Qhov no yog ib qho kev sib tw rau txhua tus tshuaj uncouplers. Txawm hais tias BAM 15 qhia tau hais tias muaj kev nyab xeeb zoo dua li DNP hauv cov qauv tsiaj, qhov kho qhov rai ntawm cov koob tshuaj zoo thiab cov koob tshuaj uas ua rau overheating (ua npaws siab) tseem yuav tsum tau hais nruj me ntsis rau tib neeg. Kev tswj hwm koob tshuaj meej thiab ntsuas qhov ntsuas kub yog qhov yuav tsum tau ua ua ntej rau txhua qhov chaw kho mob txhais lus yav tom ntej.
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