Hauj lwm lawm

Kev tsis

Taw qhia

ACE0313

musclepic 3

Khoom Description

1. Taw qhia

Raws li kev tsim qauv, ACE-031 yog tsim los ntawm kev sib txuas ntawm thaj chaw sib txuas ntxiv ntawm cov myostatin receptor (ActRIIB) nrog Fc fragment ntawm tib neeg immunoglobulin IgG1. Qhov kev tsim qauv no muab nws ob qho tib si muaj txiaj ntsig zoo rau kev sib khi thiab lub plasma ntev ib nrab -lub neej, yog li ua kom nws cov bioavailability thiab stability. Raws li cov khoom siv zoo peptide raw khoom, ACE-031 muaj ob qho kev tshawb fawb txog kev tshawb fawb thiab cov peev xwm kho mob, thiab tau dhau los ua ib qho ntawm cov tseem ceeb hauv cov leeg nqaij loj hlob thiab kev tshawb fawb metabolism.

2. Kev faib tawm thiab kev siv

Raws li nws cov kev siv thiab cov qauv tsim, ACE-031 tuaj yeem muab faib ua pawg hauv qab no:

Pharmaceutical-qib ACE-031: Feem ntau yog siv rau hauv kev tshawb fawb preclinical thiab tshuaj txhim kho theem. Nws cov purity feem ntau yog siab dua 98%, uas tsim los siv cov txheej txheem ntawm cov xov tooj ntawm tes (xws li CHO hlwb), thiab ua kom huv huv thiab cov txheej txheem tswj kom zoo. Cov khoom no yuav tsum ua tau raws li GMP cov qauv thiab siv rau kev sim kho cov kab mob xws li cov leeg nqaij dystrophy thiab mob qog noj ntshav.

Kev tshawb fawb -qib ACE-031: Siv dav hauv molecular biology, pharmacology, thiab cell signaling pathway research. Cov qib no yog qhov tseem ceeb tshaj plaws ntawm kev ua haujlwm thiab cov khoom sib xws-rau-batch sib xws, siv los txheeb xyuas cov txheej txheem ntawm kev ua ntawm ACE-031 hauv cov leeg nqaij loj hlob, kev tswj cov pob txha ntom ntom, thiab cov metabolism hauv homeostasis. Purity feem ntau yog siab dua 95%, haum rau kev tshawb fawb tsiaj txhu.

Kev lag luam lossis qib nruab nrab qib ACE-031: Cov khoom no feem ntau yog siv rau hauv kev tsim cov qauv hauv qab los yog cov neeg nruab nrab rau kev hloov kho cov qauv. Txawm hais tias purity qis me ntsis (90-95%), lawv tseem muaj txiaj ntsig zoo hauv kev tshawb fawb kev lag luam thiab tshuaj lom neeg ua kom zoo.

3. Physicochemical Properties

ACE-031 yog ib qho nruab nrab-rau-loj molecular hnyav protein / peptide compound nrog cov yam ntxwv ntawm lub cev:

Molecular Formula: C₂₆₈₆H₄₁₆₂N₇₁₄O₈₃₁S₁₆ (Theoretical molecular formula, cov mis tshwj xeeb yuav txawv me ntsis nyob ntawm qhov qhia tawm)

Molecular Luj: Kwv yees li 95-105 kDa (nyob ntawm qib glycosylation)

Cov yam ntxwv ntawm tus yam ntxwv: Ib qho dimer fusion protein uas tsim los ntawm extracellular domain ntawm ActRIIB thiab Fc ntu ntawm IgG1, nthuav tawm cov qauv symmetrical ruaj khov thiab zoo peb -dimensional conformational stability.

Isoelectric Point (pI): Kwv yees li 6.8 txog 7.2

Solubility: Soluble nyob rau hauv PBS tsis, physiological saline, thiab buffer systems uas muaj 0.1% Tween-20; insoluble nyob rau hauv cov organic solvents.

Kev ruaj ntseg: Hauv nws daim ntawv lyophilized hmoov, nws tuaj yeem ruaj khov ntawm -20℃rau ntau tshaj ob xyoos; nyob rau hauv daim ntawv tshuaj, nws tuaj yeem khaws cia ntawm 4℃rau kwv yees li ob lub lis piam.

Zoo li - ntse, ACE-031 yog dawb los yog tawm -dawb lyophilized hmoov nrog lub teeb thiab zoo zoo nkauj thiab tsis tshua muaj hygroscopicity. Tom qab dissolving, nws tsim cov xim tsis muaj xim, pob tshab, los yog me ntsis milky-dawb tov. Yog hais tias cov xim yog daj los yog turbid, nws feem ntau qhia tau hais tias cov protein tau undergone ib nrab degradation los yog aggregation.

4. Mechanism of Action

Lub luag haujlwm tseem ceeb ntawm kev ua ntawm ACE-031 yog ua raws li nws cov haujlwm thaiv kev tiv thaiv myostatin thiab lwm yam kev taw qhia. Myostatin yog ib qho cytokine ntawm tsev neeg TGF thiab qhov tsis zoo uas tswj cov leeg pob txha loj hlob. ACE-031 sib tw khi rau myostatin thiab activin A ligands, tiv thaiv lawv los ntawm kev khi rau lub ntuj ActRIIB receptor, yog li thaiv nws txoj hauv qab Smad2/3 signaling pathway, yog li txhawb cov leeg nqaij protein synthesis thiab txo cov leeg nqaij.

Tsis tas li ntawd, kev tshawb fawb tau pom tias ACE-031 tuaj yeem:

nce nqaij fiber ntau txoj kab uas hla thiab ceev;

txhim kho pob txha pob txha cov ntsiab lus thiab pob txha ceev;

tswj lipid metabolism thiab insulin rhiab heev;

thiab ua qauv qhia tseem ceeb los tiv thaiv- nqaij atrophy thiab tiv thaiv- cov pob txha poob hauv kev sim tsiaj.

Cov khoom no ua rau ACE-031 tsis yog tsuas yog muaj peev xwm kho tau tab sis kuj yog lub cuab yeej molecular tseem ceeb rau kev kawm cov leeg nqaij metabolism thiab rov tsim dua tshiab.

5. Qhov zoo thiab yam ntxwv

High Bioactivity thiab Specification

Los ntawm lub hom phiaj khi rau ActRIIB ligand, ACE-031 nthuav tawm cov kev sib raug zoo heev thiab kev xaiv ntawm qib molecular, cuam tshuam cov teeb meem myogenic inhibitory, yog li txhim kho cov leeg nqaij synthesis.

Kev ua tau zoo ntawm Pharmacokinetic

Fc fusion qauv ua rau nws ntev dua ib nrab ntawm -lub neej hauv vivo, tso cai rau nws cov haujlwm hauv cov tsiaj mus ntev li ob peb hnub, txo qhov zaus ntawm kev tswj hwm.

High Purity thiab Tsawg Immunogenicity

Ua los ntawm kev siv cov kab mob ntawm tes ntawm tes, nws qhov kev hloov kho glycosylation yog ze rau ntawm tib neeg cov proteins, uas ua rau muaj kev tiv thaiv kab mob tsawg.

Zoo Stability thiab Formulation Applicability

Cov ntaub ntawv nyoos hmoov yog ib qho yooj yim rau khaws thiab thauj, thiab tuaj yeem yaj tau yooj yim hauv cov txheej txheem tsis sib xws los npaj cov tshuaj txhaj tshuaj lossis lwm yam tshuaj.

Muaj peev xwm kho mob daim ntawv thov Prospects

Ntau yam kev sim tsiaj thiab cov ntaub ntawv kho mob thaum ntxov tau pom tias ACE-031 tuaj yeem ua rau cov nqaij pob txha thiab pob txha pob txha pob txha pob txha, uas qhia txog kev cia siab dav hauv kev kho mob ntawm cov leeg nqaij dystrophy thiab osteoporosis.

6. Kev tsim khoom thiab kev tswj xyuas zoo

ACE-031 feem ntau yog qhia nyob rau hauv CHO (Suav hamster zes qe menyuam) hlwb siv gene recombination technology. Cov txheej txheem ntau lawm suav nrog:

Tsim cov fusion gene thiab qhia nws mus rau hauv kev qhia vector;

Ua kom muaj kev qhia siab hauv cell kab lis kev cai;

Purification los ntawm protein A affinity chromatography thiab ion exchange chromatography;

Frecrystallization thiab aseptic ntim.

Rau kev tswj kom zoo, ntau txoj hauv kev yuav tsum tau kuaj:

SDS-PAGE: Txhawm rau ntsuas kev ua kom huv huv thiab kev tsim dimer;

Western Blot: Kom paub meej Fc fusion qauv;

Kev tshuaj xyuas HPLC: txhawm rau txheeb xyuas qhov purity thiab homogeneity;

Kev kuaj Endotoxin: Txhawm rau kom ntseeg tau tias cov ntsiab lus endotoxin qis dua qhov txwv kev nyab xeeb;

Bioactivity test: txhawm rau txheeb xyuas nws qhov muaj peev xwm inhibitory ntawm Myostatin signaling txoj hauv kev.

7. Cia thiab tuav cov xwm txheej

Cov hmoov lyophilized yuav tsum khaws cia hauv qab −20℃nyob rau hauv ib qho teeb pom kev zoo - pov thawj thiab noo noo - pov thawj ib puag ncig. Tom qab rov kho dua, nws yuav tsum tau ua raws li kev mob aseptic. Rau luv - lub sij hawm cia, qhov kub ntawm 4℃yog pom zoo. Tsis txhob rov khov dua -thaw cycles los tiv thaiv kev sib sau ua ke los yog inactivation. Rau lub sijhawm ntev - khaws cia, cov tshuaj yuav tsum tau aliquoted thiab sai khov ntawm −80℃.

8. Kev nyab xeeb thiab ceev faj

Hauv kev tshawb fawb tsiaj thiab kev sim tshuaj thaum ntxov, ACE-031 feem ntau pom muaj kev nyab xeeb zoo, tab sis yuav tsum tau ceev faj hauv qab no:

Cov tshuaj tiv thaiv vasodilatory me me los yog ntshav ntswg tuaj yeem tshwm sim vim muaj kev cuam tshuam me ntsis ntawm cov cim angiogenesis los ntawm ACE-031;

Ntev - lub sij hawm siab - kev siv koob tshuaj yuav cuam tshuam rau kev sib npaug ntawm cov tshuaj hormones;

Kev nyab xeeb ntawm kev siv rau cov tib neeg uas tsis muaj zog tiv thaiv kab mob yuav tsum tau ua tib zoo soj ntsuam.

Kev tshawb fawb- cov khoom qib yog rau kev sim siv nkaus xwb thiab yuav tsum tsis txhob siv rau kev txhaj tshuaj tib neeg lossis kev kho mob.

9. Cov tsos mob thiab kev soj ntsuam zoo

High - zoo ACE-031 hmoov yuav tsum yog ib qho dawb los yog me ntsis mis nyuj dawb lyophilized loj, ruaj khov nyob rau hauv huab cua, thiab yuav tsum tsis txhob muaj qhov tseem ceeb noo noo nqus los yog clumping. Cov tshuaj yaj yeeb yuav tsum meej thiab pob tshab. Yog tias turbidity, nag lossis daus ntawm cov xim tshwm sim, nws qhia tau hais tias muaj protein ntau denaturation los yog paug, thiab cov khoom yuav tsum tsis txhob siv. Cov khoom lag luam zoo yuav tsum qhia ib pawg tseem ceeb hauv electrophoresis, tsis muaj qhov pom tseeb ntawm lwm cov proteins.

10. Cov ntsiab lus thiab cov kev cia siab yav tom ntej

ACE-031, raws li high-end recombinant peptide biologic, tau dhau los ua cov cuab yeej tseem ceeb hauv kev tshawb fawb txog kev loj hlob ntawm cov leeg vim nws cov qauv tsim zoo tshaj, ruaj khov physicochemical zog, thiab muaj txiaj ntsig lom neeg muaj txiaj ntsig zoo. Nws tsis tau tsuas yog nce qib kev nkag siab ntawm myogenic inhibition mechanisms tab sis kuj tau coj cov lus qhia tshiab rau kev kho mob ntawm ntau cov leeg nqaij atrophy.

Nyob rau hauv lub neej yav tom ntej, nrog rau kev nce qib hauv protein engineering thiab ntev -kev tsim cov thev naus laus zis, ACE-031 yuav tsum tau ua kom zoo dua nws ib nrab-lub neej thiab lub hom phiaj, thiab tej zaum yuav ua ke nrog kev kho noob caj noob ces thiab qia cell kho los tsim kev kho cov leeg nqaij. Nyob rau tib lub sijhawm, tsis tu ncua kev txhim kho cov qauv zoo thiab kev ntsuas kev nyab xeeb yuav ua kom nws cov ntawv thov kev ntseeg siab hauv kev tshawb fawb thiab kev lag luam tshuaj.

Zuag qhia tag nrho, ACE-031 sawv cev rau txoj kev loj hlob ntawm ib tiam tshiab ntawm bioactive peptides. Nws zoo heev physicochemical zog, dav daim ntawv thov prospects, thiab scientific npaj system ua rau nws yog ib qho tseem ceeb choj txuas mus rau scientific kev tshawb fawb thiab kev kho mob txhais lus.