AB 9604 5 mg

▎ AOD 9604 Qauv

Source: PubChem

Sequence: SALLRSIPAPAGASRLLLLTGEIDLP Molecular Formula: C 78H 123N 23O 23S2 Molecular Luj: 1815.1g/mol CAS Nr .: 221231-10-3 PubChem CID: 71300630

▎ AOD 9604 Kev Tshawb Fawb

Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm AOD 9604?

AOD 9604 yog peptide tsim los ntawm C-terminal fragment ntawm tib neeg kev loj hlob hormone (hGH), tshwj xeeb tshaj yog cov amino acid sequence 177 - 191, nrog rau ntxiv tyrosine residue ntawm N-terminus ntawm peptide.

Kev sib raug zoo ntawm AOD 9604, kev loj hlob hormone, thiab kev kho mob rog yog raws li hauv qab no. Txawm hais tias tib neeg txoj kev loj hlob hormone (hGH) muaj peev xwm los kho kev rog, cov teeb meem kev nyab xeeb txwv nws txoj kev siv mus ntev. Raws li C-terminal fragment ntawm hGH, AOD 9604 raug suav hais tias muaj peev xwm ua lub luag haujlwm hauv kev kho mob rog yam tsis ua rau muaj qhov tsis zoo ntawm hGH. Cov kev tshawb fawb tau pom tias ob qho tib si hGH thiab AOD 9604 tuaj yeem ua rau poob phaus thiab nce lipolytic rhiab heev tom qab kev kho mob ntev hauv cov nas. Ib qho kev ua tau zoo yog los ntawm kev cuam tshuam nrog β-adrenergic txoj hauv kev, tshwj xeeb tshaj yog nrog beta (3)-adrenergic receptors (β3-AR) ^[1] .

Ob leeg hGH thiab AOD 9604 tuaj yeem txo lub cev qhov hnyav thiab lub cev rog ntawm cov nas rog rog, thiab qhov tshwm sim no cuam tshuam nrog kev nce qib ntawm β3-AR RNA, lub ntsiab lipolytic receptor hauv adipocytes. Qhov tseem ceeb, ob qho tib si hGH thiab AOD 9604 tuaj yeem nce qib β3-AR RNA hauv cov nas rog rog mus rau qib piv rau cov nas ntshiv ^[1] .

Txawm li cas los xij, hauv β3-AR knockout nas, kev siv ntev ntev ntawm hGH thiab AOD 9604 ua tsis tiav los tsim qhov hnyav hloov thiab nce lipolysis pom hauv cov tsiaj qus tswj nas. Tab sis hauv kev sim mob hnyav, AOD 9604 tuaj yeem ua rau muaj zog noj thiab rog oxidation hauv β3-AR knockout nas ^[1].

Kev kho mob osteoarthritis: Intra-articular txhaj ntawm AOD 9604 tau qhia qee yam kev kho mob hauv tus qauv luav ntawm osteoarthritis. Kev tshawb fawb los ntawm Kwon Dong Rak thiab Park Gi Young qhia tau hais tias ultrasound-guided intra-articular txhaj ntawm AOD 9604 txhim kho pob txha mos, thiab kev txhaj tshuaj ua ke ntawm AOD 9604 thiab hyaluronic acid (HA) zoo dua siv HA lossis AOD 9604 ib leeg ^[2] .

AOD 9604 tau raug tshaj tawm los ua cov khoom lipolytic ntawm kev loj hlob hormone yam tsis muaj kev phiv los ntawm inducing ntshav qab zib. Yog li ntawd, nws tuaj yeem siv los ua cov tshuaj txhawb kev ua tau zoo thiab raug txwv los ntawm Lub Koom Haum Ntiaj Teb Kev Tiv Thaiv-doping (WADA) ^[3].

Kev tshawb fawb keeb kwm ntawm AOD 9604 feem ntau tshwm sim los ntawm qhov tsis sib xws ntawm qhov muaj peev xwm ntawm tib neeg kev loj hlob hormone hauv kev kho mob rog thiab nws cov teeb meem kev nyab xeeb. Nyob rau tib lub sijhawm, nrog kev nce hauv cov kab mob metabolic, nws lub luag haujlwm tseem ceeb hauv kev txhim kho metabolic kev noj qab haus huv thiab nws txoj kev nyab xeeb tau dhau los ua qhov tseem ceeb ntawm kev tshawb fawb.

Dab tsi yog cov yam ntxwv thiab qhov zoo ntawm cov txheej txheem ntawm kev ua ntawm AOD 9604 hauv kev poob phaus thiab kev tswj cov metabolism?

Ua ntej ntawm tag nrho cov, nyob rau hauv cov nqe lus ntawm lipolysis, AOD 9604 ho txhim khu lub rhiab heev ntawm lipolysis los ntawm activating β3-adrenergic receptor (β3-AR) txoj kev ntawm adipocytes. Qhov kev ua haujlwm no ua rau adipocytes ua kom zoo dua zom cov triglycerides rau hauv cov rog dawb thiab glycerol, yog li txhawb kev decomposition thiab siv roj los muab lub zog rau lub cev. Cov txheej txheem no tsis tsuas yog pab txo qis cov rog hauv lub cev tab sis kuj txhim kho lub cev cov rog, txo qhov feem pua ​​​​ntawm cov roj visceral, thiab yog li txo qhov kev pheej hmoo ntawm ntau yam kev rog rog, xws li kab mob plawv thiab ntshav qab zib hom 2.

Thib ob, AOD 9604 kuj ua tau zoo hauv inhibiting lipogenesis. Nws tuaj yeem tiv thaiv cov rog los ntawm kev noj zaub mov los ntawm kev hloov mus rau hauv lub cev rog los ntawm kev tswj cov kev qhia ntawm cov noob ntsig txog lipogenesis. Tshwj xeeb, AOD 9604 tuaj yeem cuam tshuam cov haujlwm ntawm cov lipogenic enzymes tseem ceeb xws li fatty acid synthase, yog li txo cov synthesis thiab khaws cia ntawm fatty acids. Cov nyhuv inhibitory no pab txo qis kev loj hlob thiab kev sib txawv ntawm adipocytes thiab tiv thaiv kev nthuav dav ntawm cov ntaub so ntswg adipose, yog li ua tiav cov txiaj ntsig ntawm kev poob phaus. Nyob rau tib lub sijhawm, cov nyhuv inhibitory no tseem tuaj yeem pab tswj qhov sib npaug ntawm lub cev cov roj metabolism thiab zam cov kab mob metabolic uas tshwm sim los ntawm cov rog ntau dhau.

Hais txog kev tswj hwm cov metabolism, lub luag haujlwm ntawm AOD 9604 yog qhov nyuaj dua thiab ua tiav. Nws tuaj yeem hloov pauv lub cev lub zog metabolism los ntawm cov piam thaj metabolism mus rau cov roj metabolism, thiab qhov kev hloov pauv no tseem ceeb heev rau kev poob phaus thiab txhim kho kev noj qab haus huv metabolic. Los ntawm kev ua kom cov oxidative decomposition ntawm fatty acids, AOD 9604 muab ntau lub zog rau lub cev thiab txo qhov kev cia siab ntawm cov piam thaj metabolism. Cov kev cai metabolic no tsis tsuas yog pab txhawb cov basal metabolic tus nqi, ua rau lub cev noj ntau zog thaum so, tab sis kuj txhim kho insulin rhiab heev, txhawb nqa thiab siv cov piam thaj, thiab yog li tswj kev ruaj ntseg ntawm cov ntshav qab zib. Tsis tas li ntawd, cov txheej txheem metabolic no tseem tuaj yeem pab txo qis cov rog rog hauv lub cev xws li daim siab, tiv thaiv thiab txhim kho cov kab mob metabolic xws li rog rog.

Thaum kawg, AOD 9604 muaj qhov zoo tshwj xeeb hauv kev txo cov tshuaj insulin. Piv nrog rau qhov ua tiav cov tshuaj hormones, AOD 9604 tshem tawm cov kev mob tshwm sim uas tuaj yeem ua rau insulin tsis kam thiab nce ntshav qab zib. Qhov kev txhim kho no ua rau AOD 9604 muaj kev nyab xeeb dua thaum lub sijhawm kho thiab yuav tsis muaj kev cuam tshuam rau cov ntshav qab zib. Qhov no muaj qhov tseem ceeb hauv kev kho mob rau cov neeg mob rog, tshwj xeeb tshaj yog cov neeg muaj insulin tsis kam lossis ntshav qab zib txawv txav. AOD 9604 tsis tuaj yeem pab lawv poob phaus xwb tab sis kuj tseem txhim kho cov tshuaj insulin, txo qhov kev pheej hmoo ntawm kev mob ntshav qab zib hom 2, thiab txhim kho tag nrho cov metabolism hauv kev noj qab haus huv.

Nyob rau hauv xaus, AOD 9604 exerts nws cov teebmeem ntawm poob phaus thiab metabolic kev tswj los ntawm ntau yam mechanisms ntawm kev txiav txim, muab ib tug tshiab kev xaiv thiab kev cia siab rau kev kho mob ntawm rog rog thiab metabolic kab mob.

Qhov cuam tshuam ntawm AOD9604 ntawm kev nce lub cev hnyav ntawm Zucker (fa/fa) nas. Cov tsiaj kuaj (p) tau muab txhua hnub ib koob tshuaj ntawm qhov ncauj ntawm 500 Ìg ntawm AOD9604 ib lub cev hnyav rau 20 hnub, thiab cov tsiaj tswj (P) tau txais qhov sib npaug ntawm cov kua qaub txhua hnub hauv qhov zoo ib yam. Cov txiaj ntsig yog txhais tau tias B SEM ntawm 8 tus tsiaj. Qhov sib txawv tseem ceeb yog qhia nrog lub hnub qub.

Source: PubMed ^[5]

Dab tsi yog cov kev sib txuas tshwj xeeb los ntawm AOD 9604 cuam tshuam rau cov metabolism hauv rog?

Kev cuam tshuam nrog β-adrenergic txoj hauv kev: Kev tshawb fawb tau pom tias hGH thiab cov lipolytic fragment AOD 9604 ua los ntawm nws C-terminal tuaj yeem ua rau poob phaus thiab nce lipolytic rhiab heev tom qab kev kho mob ntev hauv nas ^[4] . Ib qho kev ua tau zoo yog los ntawm kev sib cuam tshuam nrog β-adrenergic txoj hauv kev, tshwj xeeb tshaj yog nrog β₃-adrenergic receptor (β₃-AR). Hauv cov nas rog rog, hGH thiab AOD 9604 tuaj yeem nce qib kev qhia ntawm β₃-AR RNA thiab tuaj yeem nce qib β₃-AR RNA hauv cov nas rog rog mus rau qib piv rau cov nas lean. Txawm li cas los xij, kev kho mob mus sij hawm ntev ntawm β₃-AR knockout nas nrog hGH thiab AOD 9604 ua tsis tiav los tsim qhov hnyav hloov thiab nce lipolysis pom hauv cov tsiaj qus tswj nas. Tab sis hauv kev sim mob hnyav, AOD 9604 tuaj yeem ua rau muaj zog noj thiab rog oxidation hauv β₃-AR knockout nas. Qhov no qhia tau hais tias cov teebmeem lipolytic ntawm hGH thiab AOD 9604 tsis ncaj qha los ntawm β₃-AR, txawm hais tias ob leeg tuaj yeem nce qhov kev qhia ntawm β₃-AR, uas tuaj yeem pab txhim kho lipolytic rhiab heev.

Ua kom muaj roj oxidation thiab stimulating lipolysis: Hauv rog (ob / ob) thiab lean C57BL / 6J nas, cov teebmeem ntawm tib neeg txoj kev loj hlob hormone (hGH) thiab AOD 9604 (C-terminal fragment of hGH) tuaj yeem pom ntawm lub cev qhov hnyav, lub zog sib npaug, thiab substrate oxidation tus nqi. Ob leeg hGH thiab AOD 9604 txo qhov hnyav nce ntawm cov nas rog rog, uas muaj feem xyuam rau cov roj oxidation hauv lub cev thiab nce qib plasma glycerol (qhov taw qhia ntawm lipolysis). Tsis zoo li hGH, AOD 9604 tsis ua rau hyperglycemia lossis txo qis cov tshuaj insulin. AOD 9604 tsis sib tw nrog hGH receptor thiab tsis ua rau cov cell proliferation zoo li hGH. Qhov no ntxiv kev lees paub lub tswv yim ntawm hGH ua ib qho prohormone, qhia tias cov fragment ntawm hGH tuaj yeem ua raws li kev sib txawv ntawm txoj kev hGH stimulation ib txwm ^[4] .

Dab tsi yog qhov cuam tshuam ntawm AOD 9604 ntawm daim siab?

Cov txiaj ntsig ntawm AOD 9604 ntawm daim siab yog feem ntau cuam tshuam rau hauv nws cov kev tswj hwm ntawm cov roj metabolism. Raws li ib tug hluavtaws polypeptide uas ua raws li cov lipolytic functional domain ntawm tib neeg kev loj hlob hormone (hGH), AOD 9604 tuaj yeem txhawb lipolysis, inhibit lipogenesis, thiab hloov lub cev lub zog metabolism los ntawm cov piam thaj metabolism mus rau cov roj metabolism. Cov txheej txheem ntawm kev ua no pab txo qis cov rog hauv daim siab, yog li muab qee qhov kev tiv thaiv rau daim siab. Rau cov kab mob metabolic xws li daim siab rog, qhov poob phaus thiab kev tswj cov metabolism hauv AOD 9604 tuaj yeem pab txhim kho cov roj metabolism hauv lub siab, txo lub nra ntawm daim siab, thiab yog li txhim kho daim siab ua haujlwm. Txawm li cas los xij, tam sim no muaj qee qhov kev tshawb fawb ncaj qha txog cov txiaj ntsig ntawm AOD 9604 ntawm daim siab. Cov teebmeem saum toj no feem ntau yog kwv yees raws li nws cov txiaj ntsig ntawm cov roj metabolism, thiab kev tshawb fawb ntau ntxiv tseem xav tau los txheeb xyuas cov kev tiv thaiv lub siab tshwj xeeb thiab cov txheej txheem ntawm kev ua.

Dab tsi yog qhov tseem ceeb ntawm AOD 9604?

AOD 9604 yog ib qho hluavtaws polypeptide uas ua raws li lipolytic kev ua haujlwm ntawm tib neeg txoj kev loj hlob hormone (HGH), thiab nws daim ntawv thov kev kho mob tseem ceeb. Hauv kev kho mob rog thiab cov kab mob metabolic, AOD 9604 tuaj yeem txhawb nqa lipolysis, inhibit lipogenesis, thiab tswj lub cev cov txheej txheem metabolic, pab cov neeg mob rog rog, txhim kho lub cev muaj pes tsawg leeg, thiab muaj peev xwm siv tau rau hauv kev kho mob ntawm cov kab mob metabolic xws li fatty siab. Piv nrog rau qhov ua tiav cov tshuaj hormones loj hlob, nws tshem tawm cov kev mob tshwm sim uas tuaj yeem ua rau insulin tsis kam thiab nce ntshav qab zib, yog li nws muaj kev nyab xeeb dua thaum lub sijhawm kho thiab tsim nyog rau ntau tus neeg mob.

AOD 9604 muaj qhov tseem ceeb hauv kev tshawb fawb thiab kev tsim tshuaj yeeb. Raws li cov tshuaj poob phaus nrog cov txheej txheem tshwj xeeb ntawm kev ua, nws muab cov kev xaiv tshiab rau kev kho mob rog rog, ua kom pom lub peev xwm ntawm cov tshuaj polypeptide hauv kev kho cov kab mob metabolic, thiab muab cov tswv yim tshiab thiab cov lus qhia tshawb fawb rau kev txhim kho tom ntej ntawm kev nyab xeeb thiab zoo dua cov tshuaj poob phaus. Tsis tas li ntawd, kev sib txuas thiab kev tshawb fawb ntawm AOD 9604 tau txhawb txoj kev loj hlob ntawm thaj chaw ntawm cov tshuaj polypeptide, tshawb xyuas qhov ua tau ntawm cov tshuaj polypeptide hauv kev ua thiab tswj cov kev ua haujlwm ntawm lub cev hauv lub cev, thiab muab cov kev paub tseem ceeb rau kev tsim, kev sib txuas, thiab kev ua kom zoo ntawm cov tshuaj polypeptide.

Hauv kev txhawb nqa txoj kev noj qab haus huv, AOD 9604 tuaj yeem siv los ua tus pabcuam pabcuam los pab tib neeg tswj lawv qhov hnyav thiab tswj lub xeev noj qab haus huv. Kev rog rog yog ib qho teeb meem loj hauv lub neej niaj hnub no, thiab nws qhov kev poob phaus tuaj yeem muab kev txhawb nqa ntxiv rau cov neeg uas muaj teeb meem poob phaus los ntawm kev noj zaub mov yooj yim thiab kev tawm dag zog. Nyob rau tib lub sijhawm, los ntawm kev tswj cov roj metabolism, nws pab txhim kho lub cev metabolism hauv kev noj qab haus huv, txo cov ntshav lipid, txo cov rog rog hauv cov hlab ntsha, txo cov kev pheej hmoo ntawm cov kab mob metabolic xws li kab mob plawv, thiab txhim kho lub neej zoo.

AOD 9604 kuj tseem ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa kev tshawb fawb hauv paus. Nws txoj kev tshawb fawb pab tshawb nrhiav tob tob txog cov txheej txheem ntawm kev ua haujlwm ntawm tib neeg kev loj hlob hormone, tshwj xeeb tshaj yog nws lub luag haujlwm tshwj xeeb thiab qhia txoj hauv kev hauv kev tswj hwm cov roj metabolism. Los ntawm kev tshawb fawb ntawm AOD 9604, cov kws tshawb fawb tuaj yeem nkag siab zoo dua li cas kev loj hlob hormone exerts nws lub cev muaj zog los ntawm kev sib cuam tshuam ntawm cov domains thiab receptors, thiab yuav ua li cas cov haujlwm no hloov pauv raws li qhov sib txawv ntawm lub cev thiab kab mob. Tsis tas li ntawd, AOD 9604 tuaj yeem siv los ua cov cuab yeej tshawb fawb rau kev tshawb fawb txog cov roj metabolism, pab cov kws tshawb fawb tshawb fawb txog cov txheej txheem ntawm cov rog decomposition, tiam, thiab cov teeb liab hloov pauv ntawm tes, nthuav tawm cov txheej txheem molecular thiab kev tswj hwm kev sib txuas ntawm cov roj metabolism, thiab muab lub hauv paus theoretical rau kev txhim kho txoj kev kho mob thiab tshuaj rau cov rog metabolism.

Tus sau phau ntawv xov xwm

Heffernan, MA koom nrog University of Limerick thiab muaj kev koom tes hauv ntau yam kev kawm. Cov no suav nrog Endocrinology & Metabolism, qhov twg kev tshawb fawb yuav tsom mus rau cov haujlwm hormonal thiab cov txheej txheem metabolic hauv lub cev. Hauv Polymer Science, lawv txoj haujlwm tuaj yeem koom nrog kev kawm ntawm cov ntaub ntawv polymer, lawv cov khoom sib txuas, cov khoom, thiab kev siv. Physiology yuav npog cov dej num thiab cov txheej txheem ntawm cov kab mob nyob, thaum Nutrition & Dietetics cuam tshuam txog kev tshawb fawb ntawm zaub mov, khoom noj khoom haus, thiab kev coj noj coj ua.

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

Heffernan txoj kev tshawb fawb tuaj yeem tshawb txog cov kev sib tshuam ntawm cov teb no, xws li tsim cov tshuaj polymer-raws li kev xa khoom rau cov kab mob metabolic lossis kawm txog kev cuam tshuam ntawm lub cev ntawm cov khoom noj khoom haus siv cov txheej txheem kev tshawb fawb qib siab. Lawv txoj haujlwm ua rau muaj kev nkag siab tob txog cov txheej txheem lom neeg thiab kev tsim kho tshiab hauv kev kho mob thiab khoom siv science. Heffernan, MA tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [4].

▎ Cov Lus Qhia Tseem Ceeb

[1] Heffernan M, Summers RJ, Thorburn A, et al. Cov teebmeem ntawm tib neeg GH thiab nws cov lipolytic fragment (AOD9604) ntawm lipid metabolism tom qab kev kho mob ntev hauv cov nas rog rog thiab β3-AR knock-out nas[J]. Endocrinology, 2001,142(12):5182-5189.DOI:10.1210/en.142.12.5182.

[2] Kwon DR, Park G Y. Cov nyhuv ntawm Intra-articular Txhaj ntawm AOD9604 nrog lossis tsis muaj Hyaluronic Acid hauv Luav Osteoarthritis Model[J]. Annals of Clinical and Laboratory Science, 2015,45(4):426-432. http://www.annclinlabsci.org/content/45/4/426.long

[3] Cox HD, Smeal SJ, Hughes CM, et al. Kev kuaj pom thiab hauv vitro metabolism ntawm AOD9604 [J]. Kev Ntsuas Tshuaj thiab Tshuaj Ntsuam Xyuas, 2015,7(1):31-38.DOI:10.1002/dta.1715.

[4] Heffernan MA, Thorburn AW, Fam B, et al. Ua kom muaj roj oxidation thiab poob phaus hauv cov nas rog rog tshwm sim los ntawm kev kho mob ntev nrog tib neeg txoj kev loj hlob hormone lossis hloov C-terminal fragment [J]. International Journal of Obesity, 2001,25(10):1442-1449.DOI:10.1038/sj.ijo.0801740.

[5] Ng FM, Sun J, Sharma L, et al. Metabolic Studies ntawm Synthetic Lipolytic Domain (AOD9604) ntawm Human Growth Hormone [J]. Hormone Research hauv Paediatrics, 2001, 53:274-278. PIB: 10.1159/000053183

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.