ACE-031 1mg/vial Neutralize Myostatin Thiab Ua kom cov leeg nqaij muaj peev xwm loj hlob

ACE-031 1mg/vial core introduction

Activin receptor IIB fusion protein|Cov leeg loj hlob regulator 1mg / vial

Lub npe: ACE-031 (ActRIIB-Fc)

English npeQauv: ACE-031

Protein qauv: Ib qho recombinant fusion protein, tsim los ntawm fusion ntawm activin receptor IIB extracellular domain thiab tib neeg IgG1 Fc fragment.

Molecular hnyav: Kwv yees li 100-120 kDa (tom qab glycosylation)

Purity: Ntau dua lossis sib npaug li 90% (SDS-PAGE/HPLC)

Cov ntsiab lus: 1 mg / fwj

Qhov tshwm sim: Dawb los yog tawm -dawb lyophilized hmoov

Cia: Txias ntawm -80 degree, tiv thaiv lub teeb, thiab khaws cia rau hauv qhov chaw qhuav.

Daim ntawv qhia kev siv thiab cia

ACE-031 (activin receptor IIB-Fc fusion protein):

ACE-031 yog ib qho recombinant fusion protein tsim los ntawm fusing lub extracellular ligand-binding domain ntawm activin receptor IIB nrog Fc fragment ntawm human immunoglobulin G1 (IgG1). Raws li ib tug soluble decoy receptor, nws khi nrog siab affinity rau thiab neutralizes tsis zoo regulators ntawm cov leeg kev loj hlob (xws li myostatin / GDF-8, activin, thiab lwm yam), yog li thaiv lawv downstream signaling txoj kev. Hauv kev sim ua qauv, qhov kev thaiv qhov thaiv no ua rau muaj kev nce ntxiv hauv cov leeg pob txha. Tsis zoo li kev txhaj tshuaj ncaj qha ntawm kev loj hlob, ACE-031 siv nws cov teebmeem los ntawm kev txo qis kev loj hlob ntawm endogenous-inhibiting signals, muab cov cuab yeej muaj zog rau kev kawm cov txheej txheem molecular ntawm cov leeg nqaij hypertrophy, nqaij atrophy kab mob (xws li Duchenne nqaij dystrophy thiab cachexia), thiab cov leeg nqaij metabolism.

Vim nws cov txheej txheem tshwj xeeb ntawm kev txhawb nqa cov leeg nqaij los ntawm kev txo cov cim endogenous inhibitory, ACE-031 tau nyiam cov neeg tshawb fawb hauv cov leeg nqaij biology, kab mob neuromuscular, cachexia (xws li mob qog noj ntshav thiab sarcopenia), thiab cov tshuaj kho dua tshiab. Piv rau cov tshuaj anabolic steroids ib txwm muaj, nws cov protein-protein kev sib cuam tshuam-raws li cov txheej txheem tuaj yeem muaj qhov sib txawv ntawm kev ua, ua rau nws yog ib qho tseem ceeb tshawb fawb cov cuab yeej hauv kev kawm txog cov kev cai ntawm cov leeg nqaij, ntsuas cov kev kho mob qog nqaij hlav tshiab, thiab tshawb nrhiav tsiaj cov qauv ntawm cov leeg nqaij sib cuam tshuam nrog lwm cov pob txha thiab cov rog (xws li).

ACE-031 Daim Ntawv Thov:

Raws li ib tug soluble decoy receptor, nws yog siv nyob rau hauv vitro thiab nyob rau hauv vivo qauv los khi nrog siab affinity thiab neutralize TGF- superfamily cov tswv cuab xws li myostatin (GDF-8) thiab activin, yog li kawm txog qhov cuam tshuam ntawm kev thaiv qhov kev taw qhia ntawm kev sib txawv ntawm myoblast, skeletal leeg nqaij thiab kev ua haujlwm. Nws yog feem ntau siv los tshawb nrhiav cov tswv yim kho mob rau cov leeg nqaij atrophy, kev kho dua tshiab tom qab cov leeg mob, thiab kev sib raug zoo ntawm cov leeg nqaij thiab lub zog metabolism.

Nws yog dav siv nyob rau hauv cov tsiaj qauv ntawm Duchenne leeg nqaij dystrophy, mob cancer cachexia qauv, kev tshawb fawb ntawm lub hnub nyoog -txog sarcopenia, thiab kev tshawb fawb ntawm cov mechanisms ntawm cov nqaij ntshiv thiab hypertrophy. Nws cov qauv tsim cov protein sib xyaw ua ke muab ib qho kev sim reagent tseem ceeb rau kev ntsuam xyuas cov peev txheej kho mob ntawm lub hom phiaj ntawm ActRIIB cov cim qhia txoj hauv kev thiab nkag siab txog cov leeg nqaij txoj kev loj hlob hauv kev tswj xyuas nruj heev.

Kev siv thiab kev khaws cia

1. Kev kho dua tshiab thiab kev npaj:

Cov kuab tshuaj pom zoo:

Nyiam cov kuab tshuaj: sterile dej rau kev txhaj tshuajlos yogsterile phosphate- buffered saline (PBS) ntawm pH 6.0-7.2. Cov kuab tshuaj acidic raug txwv nruj heev.

Lub luag haujlwm tseem ceeb: Nws raug pom zoo kom ntxiv cov khoom thauj khoom proteinrau reconstitution thiab tag nrho cov kev daws teeb meem.Sterile PBS muaj 0.1% -1% bovine serum albumin (BSA) lossis 0.1% HSApom zoo kom tiv thaiv kom txhob muaj protein ntau adsorption thiab aggregation.

Ua hauj lwm daws dilution: Dilute nrogsterile PBS uas muaj cov khoom noj muaj protein ntau.

Txwv tsis pub kiag li: Nws yog txwv tsis pub siv cov dej distilled, dej deionized, los yog cov protein ntau -dawb buffer cov kev daws teeb meem ncaj qha los npaj siab - cov ntsiab lus hauv Tshuag. Tsis txhob vortexing, nruj nreem co, los yog rov tshuab thiab agitation.

Tus txheej txheem npaj:

Solvent npaj:

Siv PBS (pH 7.0-7.2) uas tau ua kom tsis muaj menyuam lim los ntawm 0.22 μm lim membrane lossis dej tsis huv rau kev txhaj tshuaj.

Nws raug pom zoo kom ntxiv BSA lossis HSA rau cov kuab tshuaj mus rau qhov kawg ntawm 0.1% -1%.

Ua ntej- txias cov kuab tshuaj ntawm cov dej khov los yog siv cov kuab tshuaj tshiab ntawm chav tsev kub.

Reconstitution txheej txheem:

Ua cov txheej txheem hauv ib puag ncig huv. Ntxiv 1.0 mL ntawm cov kuab tshuaj pom zoo rau 1 mg vial.

Cia cov kuab tshuajkom maj mam ntws hauv lub raj mis phab ntsa, thiab zam kiag licuam ​​tshuam ncaj qha rau ntawm khov- ncuav mog qab zib qhuav.

Muab lub vial tso rau ntawm lub rooj thiabqaij thiab tig nws qeeb heevtso cai rau cov kuab tshuaj kom ntub tag nrho cov hmoov. Cia nws sawv ntsug rau 10-15 feeb kom yaj ib txwm.

Tsis txhob vortex, vibrate, los yog co hnyav.Maj mam invert kom sib tov.

Cov ntsiab lus kawg: 1 mg / mL (kwv yees li 8-12 μM, nyob ntawm qib ntawm glycosylation) cov tshuaj hauv Tshuag.

Dispensing thiab dilution:

Tam sim ntawd muab tso rau hauv ib koob ntawm 5-20 μL siv cov raj uas tsis muaj adsorption centrifuge (xws li cov raj silanized).

Yog xav tau dilution, ua serial dilutions siv PBS uas muaj cov cab kuj protein. Tsis txhob loj - nplai dilutions hauv ib kauj ruam.

Daim ntawv qhia meej: ACE-031, concentration, hnub npaj, batch naj npawb, cia kub.

Ua haujlwm concentration siv:

Kev sim hauv vitro cell: Feem ntau siv cov concentration ntau yog 1 txog 20 ug / mL (kwv yees li 10 txog 200 nM), uas yuav tsum tau ua kom zoo raws li hom cell thiab lub hom phiaj kev sim.

Tsiaj hauv vivo sim: Kev noj tshuaj yuav tsum tau txiav txim nruj raws li cov ntaub ntawv luam tawm tsiaj txhu. Feem ntau txoj kev ntawm kev tswj hwm yog txhaj tshuaj subcutaneous lossis intraperitoneal, nrog ntau npaum li cas ntawm mg / kg.Kev sim ua ntej yog yuav tsum tau ua.

Piv txwv suav: Txhawm rau npaj cov tshuaj ua haujlwm 10 ug / mL, noj 10 μL ntawm cov tshuaj 1 mg / mL thiab ntxiv rau 990 μL ntawm PBS uas muaj 0.1% BSA.

Cov ntsiab lus tseem ceeb kom nco ntsoov:

Ua tib zoo saib xyuas: Kev tuav yuav tsum maj mam maj mamkom tsis txhob tsim ua npuas ncauj, npuas, lossis shearing rog uas tuaj yeem ua rau cov protein.

Carrier protein: Nws yog ib qho tseem ceeb rau reconstitute thiab dilute lubprotein siv cov tshuaj uas muaj cov cab kuj protein, vim qhov no yog ib qho tseem ceeb los tiv thaiv cov protein los ntawm adsorbing mus rau lub thawv ntim thiab aggregation.

Slow reconstitution : Cia cov hmoov lyophilized kom yaj maj mam thiab lawmhauv cov kuab tshuaj; yog tias tsim nyog, lub sijhawm sawv ntsug tuaj yeem txuas ntxiv.

Txias-thaw lub voj voog txwv nruj heev: Rov qab khov-thaw cycles raug txwv nruj heev; cov tshuaj yuav tsum tau dispensed nyob rau hauv ib tug mus. Cov tshuaj diluted ua hauj lwm yuav tsum tau siv sai li sai tau.

Saib xyuas qhov xwm txheej: Tom qab rov kho dua, cov tshuaj yuav tsum yog qhov tseeb, tsis muaj xim lossis daj daj, thiab me ntsis khov. Lub xub ntiag ntawm cloudiness, flocculent teeb meem, los yog hais tias cov protein yuav muaj aggregated, thiab nws usability yuav tsum tau ua tib zoo soj ntsuam.

2. Cia tej yam kev mob:

Unreconstituted lyophilized hmoov:

Ntev - lub sij hawm cia: Sib sib zog nqus khov ntawm -80 degree. Tsis txhob khaws cia ntawm -20 degree.

Txee lub neej: Ntawm -80 degree, lub sijhawm khaws cia pom zoo yog 12 lub hlis.

nruj me ntsis tiv thaiv los ntawm lub teeb: Khaws rau hauv lub teeb qub-cov ntaub ntawv pov thawj aluminium ntawv ci hnab nrog lub desiccant sab hauv.

Reconstituted daws:

Kev xa tawm tam sim:Kev xa tawm yuav tsum tau uatam sim ntawd ntawm dej khovtom qab reconstitution.

Repacking thiab khov: Tom qab repacking,khaws cia ntawm -80 degreerau ntau tshaj 1 lub hlis. Ntev - lub sij hawm cia tsis pom zoo.

Kev daws teeb meem: Diluted ua hauj lwm tovyuav tsum tsis txhob khaws cia. Nws yuav tsum tau khaws cia rau hauv dej khov thiab siv rau tib hnub.

Kev thauj mus los:

Nws yuav tsum tau thaujhauv qabdej khov qhuav(-78 degree) tej yam kev mob.

Lub ntim yuav tsum xyuas kom meej tias cov khoom tseem khov nyob rau hauv tag nrho cov txheej txheem.

3. Kev ruaj ntseg thiab cov qauv ua tiav:

Physicochemical stability:

Nyob ruaj khov nyob ze - nruab nrab pH (6.0–7.5) tsis muaj kev daws teeb meem. Tsis txhob pH qhov tseem ceeb heev.

Nws yog rhiab heevmus rau mechanical stress (vortex, oscillation, bubbling) thiab rov khov dua -thaw cycles .

Nws yog rhiab heev rau deg adsorption, yog li yuav tsum tau siv cov khoom noj protein thiab cov khoom siv qis - adsorption ntim.

Txhim kho bioactivity:

Ua raws li cov ntsiab cai ntawm "maj mam tuav, kev tiv thaiv cab kuj, qeeb reconstitution, sib sib zog nqus khov, thiab nruj txwv tsis pub khov thiab thawing ".

Xav taudab tsi, thov hu raupeb

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