Kev siv GS-441524 hmoov hauv cov qauv tshawb fawb tshuaj tiv thaiv kab mob

Cov kws tshawb fawb tseem tab tom nrhiav cov tebchaw uas ua haujlwm zoo tiv thaiv kab mob nyuaj, yog li kev tshawb fawb tshuaj tiv thaiv ib txwm hloov pauv. GS-441524 tau dhau los ua cov cuab yeej tshawb fawb muaj txiaj ntsig ntawm cov nucleoside analogs uas tau txais kev saib xyuas ntau hauv chav kuaj. Qhov kev sib xyaw no, uas muaj feem cuam tshuam nrog remdesivir's active metabolite, qhia tau hais tias muaj peev xwm tiv thaiv kab mob hauv kev sim kuaj.GS-441524 hmoovyog siv los ntawm cov kws tshawb fawb thoob plaws ntiaj teb los kawm seb cov kab mob rov ua li cas, tshwj xeeb tshaj yog cov kab mob RNA. Peb tuaj yeem kawm paub ntxiv txog cov txheej txheem tshuaj tiv thaiv kab mob los ntawm kev txiav txim siab li cas qee cov tshuaj txuas nrog cov kab mob kis. Nws tsis xav tau kev tshwm sim nyob rau hauv daim teb no tam sim no uas siab - kev tshawb fawb purity- cov ntaub ntawv qib tsawg dua xav tau. Siv cov nucleoside analogue no, cov pab pawg sim ua haujlwm ntawm tus qauv mob coronavirus, tshwj xeeb yog miv irresistible peritonitis (FIP), tau tshaj tawm qhov tseem ceeb. Qhov sib xyaw ua ke yog tus qauv siv tseem ceeb hauv cov kev pab cuam tiv thaiv kab mob vim nws txwv tsis pub kis kab mob los ntawm kev ua RNA.

Peb muabGS 441524 hmoov, thov xa mus rau lub vev xaib hauv qab no kom paub meej cov lus qhia tshwj xeeb thiab cov ntaub ntawv khoom.

Khoom siv:https://www.bloomtechz.com/synthetic-chemical/organic-intermediates/gs-441524-powder-cas-1191237-69-0.html

Daim ntawv thov ntawmGS-4415 24nyob rau hauv FIP nug txog cov qauv yuav tsum tau to taub ob qho tib si kab mob pathology thiab cov compound lub biochemical zog. Cov kws tshuaj ntsuam xyuas yuav tsum tshawb xyuas seb qhov nucleoside analog tau koom nrog rau hauv kev tshawb nrhiav cov qauv li cas. Txhawm rau siv GS-441524 hauv FIP tshawb xyuas cov qauv, koj yuav tsum paub yuav luag ob qho tib si kab mob thiab cov khoom siv biochemical. Nws yog ib qho tseem ceeb rau cov kws tshuaj ntsuam xyuas seb yuav siv cov nucleoside analog li cas hauv cov phiaj xwm kev sim. Kab mob peritonitis nyob rau hauv miv yog ib qho teeb meem loj rau cov kws tshuaj ntsuam xyuas cov kab mob veterinary. Cov kab mob uas ua rau kis tus kab mob, miv tus mob coronavirus (FCoV), hloov pauv los ntawm qhov muaj kev nyab xeeb nkag mus rau qhov kev hloov pauv tsis zoo. GS-441524 hmoov yog siv rau hauv kev nug txog cov chaw kuaj mob los xav txog yuav ua li cas kis tau tus kab mob sai sai hauv cov chaw tswj.

Tsim kom muaj Viral Load Reduction Protocols

FIP antiviral nug txog pib los ntawm kev ntsuas tus qauv kis tus kabmob hauv cov zej zog ntawm tes. GS-441524 yog phosphorylated rau hauv nws cov dynamic triphosphate thav duab, sib tw nrog cov nucleotides uas muaj kab mob RNA sib xyaw thiab cuam tshuam kev rov ua dua. koob tshuaj- teb kev xav txog kev siv qPCR taug qab tus kab mob RNA ploj zuj zus nyob rau lub sijhawm, tshwm sim ntau dua- nyob ntawm kev cuam tshuam. Kev tshawb nrhiav sij hawm tshawb nrhiav pom qhov cuam tshuam thaum ntxov hauv 12-24 teev ntawm kev rov ua dua, txhawb nqa los ntawm microscopy thiab immunofluorescence tshwm sim txo qis kev cuam tshuam cytopathic. Cov tswv yim sib xyaw ua ke no muab kev nkag siab zoo ntawm cov tshuaj tiv thaiv kab mob thiab muab kev pab cuam qhia qhov zoo tshaj plaws inhibitory concentration ntau yam.

Sijhawm -Course Analysis infected Cell Cultures

Cov kws tshawb fawb tshuaj ntsuam xyuas cov zej zog tainted lub sij hawm los ntsuam xyuas cov kev cuam tshuam los tiv thaiv kab mob, tshuaj xyuas ntawm qhov sib txawv ib ntus los ntsuas cov kab mob hauv nruab nrog cev thiab cov kab mob extracellular. GS-441524 txo qhov cuam tshuam cytopathic piv rau kev tswj hwm, nrog rau kev hloov thaum ntxov pom tseeb hauv ib lub voj voog rov ua dua. Immunofluorescence thiab atomic tests pom zoo txo ​​tus kab mob antigen qhia. Kev sib piv nrog rau lwm cov nucleoside analogs muab kev pab qhia cov qauv-kev sib txuas. GS-441524 ua haujlwm raws li tus qauv siv vim nws cov khoom siv tshuaj kho mob txhim khu kev qha, txhawb kev ntsuas tus qauv ntawm cov neeg siv tshuaj tiv thaiv niaj hnub no thiab kev tshawb nrhiav kev txhim kho sai.

Cov kev tshawb fawb sib piv nrog lwm cov khoom sib xyaw

Kev sib piv ntawm ntau qhov ua tau molecules pab tshawb nrhiav cov kab mob. Labs siv GS-441524 thiab lwm yam nucleoside analogs los nrhiav kev sib txuas ntawm cov qauv thiab kev ua haujlwm. Cov kev sim sib npaug no pab cov kws tshawb fawb pom tias qhov twg ntawm cov molecules tseem ceeb tshaj plaws rau kev ua haujlwm tiv thaiv kab mob. Vim tias nws cov ntaub ntawv pharmacological paub zoo,GS-441524 hmoovtau siv los ua ib qho kev siv hauv cov kev tshawb fawb sib piv no. Cov kws tshawb fawb tuaj yeem tuaj nrog cov qauv tseem ceeb uas siv los txiav txim cov ntsiab lus tshiab. Qhov kev tsim qauv no ua rau cov txheej txheem nrhiav cov neeg sib tw zoo rau kev txhim kho ntxiv.

Lub atomic tivthaiv uas GS-441524 cuam tshuam cov kab mob sib kis suav nrog kev ua kom muaj zog enzymatic. Kev tshawb xyuas cov txheej txheem biochemical no pom tias yog vim li cas qhov sib xyaw no qhia txog kev ua haujlwm tiv thaiv kab mob tshwj xeeb. GS-441524 nres qhov kev rov ua dua ntawm cov kab mob ntawm qib atomic los ntawm kev sib txuas nrog ntau cov proteins hauv txoj hauv kev nyuaj. Los ntawm kev saib mus rau hauv cov txheej txheem biochemical no, peb tuaj yeem pom yog vim li cas qhov sib xyaw no zoo heev ntawm kev tua kab mob. RNA-dependent RNA polymerase (RdRp) yog cov tshuaj tseem ceeb uas tus mob coronaviruses siv los ua lawv tus kheej. Cov kab mob kis no tsis muaj qhov hloov pauv hloov pauv uas muaj ntau ntawm cov cell polymerases ua, uas txhais tau hais tias nucleoside analogs tuaj yeem koom nrog nws. Qhov tsis txaus ntawm cov tshuaj no yog nyob hauv plawv ntawm GS-441524 lub peev xwm los tua cov kab mob.

Hauv kev tshawb nrhiav tshuaj tiv thaiv kab mob, cov tshuaj siv tshuaj yuav tsum ua raws li cov qauv nruj kom ua kom huv, ruaj khov, thiab ua kom muaj roj ntsha. Vim nws ua tau raws li cov kev xav tau no,GS-441524 hmoovyog ib qho yuav tsum tau-muaj rau cov chaw sim ua kev tshawb fawb txog tus kabmob coronavirus. Nws txoj hauj lwm mus dhau tsuas yog kuaj xyuas cov tshuaj tiv thaiv kab mob; nws kuj suav nrog kev kawm txog yam khoom ua haujlwm li cas thiab xyuas kom meej tias cov kev xeem raug raug.

Validated Purity Standards for Experimental Consistency

 

Research-grade GS-441524 is typically confirmed at >98% purity siv HPLC tsom xam. Qhov no minimizes variability nyob rau hauv cov kev sim tau tshwm sim. Txhawb nqa cov ntaub ntawv txheeb xyuas xws li NMR thiab huab hwm coj spectrometry kom paub meej cov qauv thiab kev ntsuas kev ruaj ntseg. Kev cia kom zoo ntawm qhov kub thiab txias ua kom muaj kev ncaj ncees. High purity yog qhov tseem ceeb rau kev rov tsim dua tshiab thoob plaws cov kev tshawb fawb, tso cai rau cov txiaj ntsig zoo sib xws ntawm cov chaw sim. Cov kev tswj hwm zoo tshaj plaws no ua rau GS-441524 yog ib qho kev siv tau rau kev soj ntsuam cov tshuaj tiv thaiv kab mob hauv cov qauv kev tshawb fawb txog FIP.

Reproducible Activity hla ntau kab ntawm tes

 

GS-441524 qhia tau hais tias muaj kev tiv thaiv kab mob sib kis thoob plaws ntau lub xov tooj ntawm tes, suav nrog CRFK thiab Fcwf-4 systems. Cov qauv no txhawb nqa tus kab mob rov ua dua tshiab thiab txoj hauv kev ua haujlwm nucleoside, ua kom muaj kev ntsuam xyuas txhim khu kev qha ntawm kev ua tau zoo. Txawm hais tias metabolic sib txawv ntawm cov hom cell, cov txiaj ntsig ntawm cov tshuaj tua kab mob tseem zoo ib yam, txhawb kev rov tsim dua tshiab. Qhov kev cia siab ntawm cross-platform no ntxiv dag zog rau nws lub luag haujlwm raws li cov ntaub ntawv siv. Cov txiaj ntsig tau zoo thoob plaws cov qauv tso cai rau cov kws tshawb fawb los sib piv cov tshuaj tiv thaiv kab mob tshiab nyob rau hauv kev tswj hwm thiab rov tsim dua tshiab hauv kev tshawb fawb FIP.

Tshaj tawm Cov Ntawv Qhia Txhawb Kev Nkag Siab Mechanistic

 

Ntau tus phooj ywg- tau tshuaj xyuas cov ntaub ntawv GS-441524 cov tshuaj tiv thaiv kab mob, cov txheej txheem sim, thiab cov txheej txheem ntawm tes. Cov kev tshawb fawb thoob plaws virology, veterinary Medicine, thiab pharmacology muab cov txheej txheem txheej txheem rau cov qauv kab mob thiab kev ntsuas sib xyaw. Lub hauv paus kev paub no txhawb kev tsim cov kev tshawb fawb rov ua dua tshiab thiab pab txhawb kev tshawb nrhiav tshiab. Los ntawm kev tsim cov qauv kev sim uas tau raug lees paub, kev tshawb fawb luam tawm ua rau muaj kev sib raug zoo ntawm GS-441524 hauv kev tshawb fawb hauv chav kuaj thiab ntxiv dag zog rau nws lub luag haujlwm ua tus qauv ntsuas hauv tus kabmob coronavirus thiab FIP tshuaj tiv thaiv kev tshawb fawb.

Kab mob ntawm tes kab lis kev cai siv nyob rau hauv cov qauv kuaj tsim kev tswj ib puag ncig rau kev sim tshuaj tiv thaiv kab mob. Cov tshuab no tso cai rau koj hloov pauv yam xws li hom kab mob, tus naj npawb ntawm cov kab mob, lub sijhawm kho, thiab qhov concentration ntawm cov tshuaj. Cov ntaub ntawv sib sau ua ke pab peb nkag siab tias cov tshuaj tiv thaiv kab mob ua haujlwm li cas thiab pab peb txhim kho txoj kev peb ua cov kev sim.

Cov qauv tshuaj ntawm cov tshuaj sib txuas muaj qhov cuam tshuam loj rau lawv cov haujlwm lom neeg, tshuaj pharmacokinetics, thiab kev nyab xeeb profiles. Kev nkag siab txog kev sib txuas ntawm cov qauv thiab kev ua ub no qhia cov tshuaj chemistry kom pom cov kev kho mob zoo tshaj plaws. Cov yam ntxwv tshwj xeeb ntawm GS-441524's molecular architecture qhia tias lawv pab li cas rau nws cov khoom tiv thaiv kab mob.

Nucleobase Hloov Kho thiab RdRp Kev Paub

GS-441524 muaj cov kev hloov pauv nucleobase uas cuam tshuam kev lees paub los ntawm tus kab mob RNA-dependent RNA polymerase (RdRp). Cov qauv kev hloov pauv no sib npaug ntawm cov substrate mimicry nrog cov txiaj ntsig kev txiav tawm, cuam tshuam RNA synthesis thaum rov ua dua. Cov kws tshuaj kho mob kawm txog qhov kev hloov kho li cas cuam tshuam rau cov tshuaj tiv thaiv kab mob thiab kev xaiv. Kev ua piv txwv yog siv los kwv yees li cas cov analogs cuam tshuam nrog RdRp qhov chaw nquag, coj kev tsim cov tsev qiv ntawv sib xyaw. Cov txheej txheem no pab txhim kho cov khoom tiv thaiv kab mob kom zoo thaum txo qis - cov txiaj ntsig ntawm lub hom phiaj, txhim kho kev ua tau zoo hauv kev tsim cov tshuaj raws li cov qauv.

Qab Zib Moiety Kev Pabcuam rau Cellular Uptake

Cov qauv qab zib ribose plays lub luag haujlwm tseem ceeb hauv cellular uptake thiab phosphorylation efficiency. Kev hloov kho rau cov pab pawg hydroxyl lossis ntxiv cov lipophilic hloov pauv tuaj yeem hloov pauv cov tshuaj pharmacokinetics thiab intracellular tsub zuj zuj. GS-441524 khaws cov pawg hydroxyl uas tsis hloov pauv, ua rau nws cov hydrophilic, uas cuam tshuam rau solubility thiab membrane permeability. Cov tswv yim Prodrug ib ntus hloov kho cov pab pawg no txhawm rau txhim kho cellular nkag, nrog rau cov esterases intracellular tom qab rov ua kom cov active compound. Cov kev xav txog cov qauv no yog qhov tseem ceeb rau kev nkag siab txog kev nqus, kev ua kom muaj zog, thiab kev ua haujlwm ntawm cov tshuaj tiv thaiv tag nrho.

Phosphorylation Susceptibility thiab Metabolic Activation

GS-441524 yuav tsum tau ua ntu zus phosphorylation los ntawm cellular kinases los ua nws daim ntawv active triphosphate. Cov kauj ruam metabolic no txawv ntawm cov cell hom thiab nucleoside analog qauv. Intracellular triphosphate ntsuas pab txiav txim siab npaum li cas cov tebchaw ua haujlwm tau zoo. Kinase tshwj xeeb yog qhov tseem ceeb, vim qee cov analogs sib sau ua ke ntawm theem nrab phosphorylation, txo cov txiaj ntsig. Kev nkag siab txog cov txheej txheem metabolic no pab txheeb xyuas cov yam ntxwv uas txhim kho kev ua kom muaj zog thiab muaj zog tiv thaiv kab mob, ua kom muaj kev tsim tawm txaus ntawm cov khoom sib xyaw ua ke kom muaj txiaj ntsig zoo inhibition ntawm tus kab mob replication.

GS-441524 hmoovtxuas ntxiv ua haujlwm tseem ceeb hauv kev tshawb fawb txog tus kabmob coronavirus, txhawb nqa kev sim ua qauv, kev siv tshuaj tiv thaiv kabmob, thiab kev tsim qauv qauv. Nws zoo -cov yam ntxwv tshwj xeeb ua rau muaj kev tshawb fawb rov ua dua thoob plaws lub chaw soj nstuam thiab pab txhawb kev tsim cov tshuaj tiv thaiv kab mob tshiab. Kev tshawb fawb siv cov nucleoside analog no txhim kho kev nkag siab ntawm tus kab mob replication mechanisms thiab qhia dav dav cov tswv yim tsim tshuaj tiv thaiv. Cov qauv tsis tu ncua- kev tshawb fawb txog kev ua haujlwm thiab kev tshawb fawb siv tshuab ua rau muaj kev txhim kho tshuaj txhim kho cov txheej txheem, txhawb nqa qhov tseem ceeb ntawm cov ntaub ntawv pov thawj kev ntseeg siab hauv kev tshawb fawb txog tshuaj tiv thaiv kab mob.

1. Dab tsi yog qhov concentration ntau ntawm GS-441524 feem ntau yog siv hauv cov tshuaj tiv thaiv kab mob ntawm tes?

Thaum kuaj cov tshuaj tiv thaiv kab mob hauv cov qauv kab lis kev cai ntawm tes, cov txheej txheem tshawb fawb feem ntau siv cov concentration ntawm 0.1 txog 10 micromolar. Cov concentrations xaiv nyob ntawm seb hom cell, hom kab mob, thiab cov hom phiaj ntawm qhov kev sim. Dose-cov lus teb nkhaus ua nyob thoob plaws qhov no qhia tau hais tias kev sib xyaw ua ke cuam tshuam li cas rau kev muaj peev xwm tiv thaiv kab mob. Cov kws tshawb fawb feem ntau siv ntau dua ib qho kev xav paub txog tej yam xws li EC50 qhov tseem ceeb, uas ntsuas qhov muaj zog tiv thaiv kab mob.

2. Yuav ua li cas ruaj khov GS-441524 hmoov thaum lub sij hawm cia ntev?

High-purity GS-441524 hmoov nyob ruaj khov rau ntev tshaj li ob xyoos yog tias nws khaws cia kom zoo ntawm -20℃lossis qis dua hauv cov ntim ntim uas khaws cia kom tsis txhob ya raws. Kev tshuaj ntsuam xyuas ntawm cov khoom khaws cia tau lees paub tias tseem tsis muaj ntau qhov degradation nyob rau hauv cov xwm txheej no. Txhawm rau ua kom cov kev daws teeb meem los ntawm kev tawg tom qab ntau lub voj voog khov-thaw, cov kws tshawb fawb yuav tsum ua kom lawv tshiab lossis khaws cia lawv khov rau hauv ib qho kev siv aliquots. Kev tuav thiab khaws cov khoom sib txuas kom raug yog qhov tseem ceeb rau kev ua kom lawv nyob ruaj khov thaum sim.

3. GS-441524 puas tuaj yeem siv ua ke nrog lwm cov tshuaj tiv thaiv kab mob rau kev tshawb fawb?

Kev tshawb fawb sib xyaw ua ke yog ib qho tseem ceeb ntawm kev tshawb fawb los tsim cov kab mob tshiab. Cov kws tshawb fawb tab tom saib seb puas yog nucleoside analogs ua haujlwm zoo dua thaum ua ke nrog cov tshuaj sib xyaw ua haujlwm sib txawv, lossis yog tias lawv ua haujlwm tsis zoo. Txhawm rau txhais cov qauv kev sib raug zoo hauv kev tshawb fawb ua ke, kev sim tsim qauv yuav tsum muaj kev tswj hwm nruj thiab ua qauv lej. Cov kev tshawb fawb no pab nrhiav kev sib xyaw ua ke zoo ntawm cov tebchaw uas tuaj yeem saib hauv cov qauv kev tshawb fawb ntau dua.

BLOOM TECH muab GMP- ntawv pov thawjGS-441524 hmoov with >98% purity rau kev tshawb fawb tshuaj tua kab mob, txhawb los ntawm FDA, EU, thiab CFDA ua raws. Txhua batch suav nrog tag nrho cov ntaub ntawv txheeb xyuas (HPLC, NMR, MS) kom ntseeg tau tias muaj kev sib raug zoo rau cov koom tes thoob ntiaj teb biotech. Lub tuam txhab muab kev ruaj ntseg thiab tuav cov ntaub ntawv, cov khoom lag luam txhim khu kev qha, pob tshab tus nqi, thiab cov kev pabcuam sib xyaw ua ke, txhawb nqa ob qho kev tshawb fawb me me thiab kev tsim kho tshuaj loj. Hu rau BLOOM TECH tam sim ntawd los tham txog koj cov kev xav tau kev tshawb fawb tshwj xeeb. Peb tus qauv - nres kev pabcuam ua rau kev yuav khoom yooj yim dua thiab ua kom koj tau txais - cov ntaub ntawv zoo hauv koj thaj av - rhuav tshem cov kev xav tau ntawm kev tshawb fawb. Koj tuaj yeem thov daim ntawv pov thawj ntawm kev tsom xam, tham txog cov ntsiab lus kev, lossis muab kev txiav txim los ntawm emailSales@bloomtechz.comrau peb pab neeg tshaj lij. Cia peb pab koj nrog koj cov kev tshawb fawb antiviral. Peb qhov kev cia siab thiab kev paub tau ua rau peb GS-441524 hmoov cov neeg muag khoom xaiv rau cov tsev kawm tshawb fawb saum toj kawg nkaus thoob ntiaj teb.

1. Murphy BG, Perron M, Murakami E, Bauer K, Park Y, Eckstrand C, Liepnieks M, Pedersen NC. Cov nucleoside analog GS-441524 muaj zog tiv thaiv kab mob feline infectious peritonitis (FIP) hauv cov ntaub so ntswg kab lis kev cai thiab kev tshawb nrhiav kab mob miv. Veterinary Microbiology. 2018; 219:226-233.

2. Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, Liu H. Kev ua tau zoo thiab kev nyab xeeb ntawm nucleoside analog GS-441524 rau kev kho cov miv nrog ib txwm tshwm sim feline infectious peritonitis. Phau ntawv Journal of Feline Medicine and Surgery. 2019;21(4):271-281.

3. Yan VC, Muller FL. Qhov zoo ntawm niam txiv nucleoside GS-441524 tshaj remdesivir rau kev kho mob COVID-19. ACS Medicinal Chemistry Letters. 2020;11(7):1361-1366.

4. Dickinson PJ, Bannasch M, Thomasy SM, Murthy VD, Vernau KM, Liepnieks M, Montgomery E, Knickelbein KE, Murphy B, Pedersen NC. Kev kho tshuaj tua kab mob siv cov adenosine nucleoside analogue GS-441524 hauv cov miv uas tau kuaj pom tus kab mob neurological feline kis kab mob peritonitis. Phau ntawv Journal of Veterinary Internal Medicine. 2020;34(4):1587-1593.

5. Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R, Hui HC, Larson N. Kev kho mob ntawm me me molecule GS-5734 tiv thaiv kab mob Ebola hauv rhesus liab. Xwm . 2016;531(7594):381-385.

6. Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] asideine of3GS Ebola thiab cov kab mob tshwm sim. Phau ntawv Journal of Medicinal Chemistry. 2017;60(5):1648-1661.