Yuav ua li cas GS-441524 Powder Blocks RNA Virus Replication

Cov kab mob RNA yog ib qho teeb meem tas li hauv ob qho tib si virology thiab tsiaj tshuaj. Cov kab mob no sai sai luam lawv tus kheej hauv cov cell, uas feem ntau ua rau muaj kab mob loj heev uas nyuaj rau kev kho nrog cov tshuaj tsis tu ncua. Yuav kom ua tiav cov tshuaj, cov kws tshawb fawb yuav tsum paub tias cov tshuaj tiv thaiv kab mob ua haujlwm li cas nrog cov tshuab ntawm cov kab mob. Muaj cov nucleoside analogs uas tuaj yeem tiv thaiv kev rov ua dua ntawm cov kab mob, tab sisGS-441524 hmoov sawv tawm vim nws tuaj yeem nres RNA- nyob ntawm RNA polymerase los ntawm kev ua haujlwm. Txoj kev tshawb no saib cov txheej txheem molecular uas GS-441524 hmoov txwv tsis pub cov kab mob RNA replication. Peb saib seb cov txheej txheem kaw nws li cas rau cov nucleotides ntuj, nws cuam tshuam li cas rau kev tsim cov kab mob coronavirus RNA, thiab qhov no txhais li cas rau yav tom ntej ntawm kev tshawb fawb tshuaj tiv thaiv kab mob feem ntau. Cov kws tshawb fawb thiab cov tuam txhab tshuaj nrhiav cov khoom siv ntawm cov tshuaj no yuav kawm txog yam tseem ceeb ntawm nws ua haujlwm li cas thiab nws tuaj yeem siv tau li cas.

 

GS 441524 hmoov CAS 1191237-69-0

1. General Specification (hauv Tshuag)
(1) Txhaj tshuaj
20 mg, 6 ml; 30 mg, 8 ml; 40 mg, 10 ml
(2) Tablet
25/45/60/70 mg tab
(3) API (Ntshiab hmoov)
(4) Pill press machine
https://www.achievechem.com/pill-xwm
2.Customization:
Peb yuav sib tham tus kheej, OEM / ODM, Tsis muaj hom, rau kev tshawb nrhiav kev ruaj ntseg nkaus xwb.
GS-441524 CAS Nr .: 1191237-69-0
Kev tshuaj xyuas: HPLC, LC-MS, HNMR

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

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

Yuav ua li cas GS-441524 Hmoov Mimics Ntuj Nucleotides Thaum Viral Replication

Cov qauv zoo ib yam li Adenosine Nucleotides

Lub GS-441524 hmoov ua haujlwm raws li nucleoside analog, tshwj xeeb tshaj yog raws li adenosine analog, uas yog lub tsev thaiv ntawm RNA. Cov qauv molecular ntawm cov tshuaj cia nws dhau los ntawm thawj cov teeb meem hauv cov hlwb thiab koom nrog cov tshuab siv los ntawm cov kab mob los luam lawv tus kheej. Thaum cov kab mob RNA nkag mus rau hauv cov hlwb, lawv siv cov tswv cuab ntawm tes cov peev txheej los ua cov kab mob RNA. Nws yog ib txwm muaj rau tus kab mob RNA-dependent RNA polymerase (RdRp) enzyme los xaiv cov nucleotides ntuj xws li adenosine triphosphate (ATP) los tsim cov RNA tshiab.

Vim tias GS-441524 hmoov muaj feem xyuam rau adenosine, nws tuaj yeem sib tw nrog cov nucleotides ntuj los ua ib feem ntawm RNA chains uas loj tuaj. Tus kab mob polymerase tsis tuaj yeem qhia qhov txawv ntawm cov analog thiab adenosine tiag tiag, uas ua rau muaj kev sib tw sib tw. Lub molecule mus los ntawm cytoplasmic phosphorylation, hloov mus rau hauv nws active triphosphate daim ntawv. Qhov no ua rau nws muaj feem ntau khi rau RdRp qhov chaw nquag.

Metabolic Activation nyob rau hauv Host Cells

GS-441524 hmoov yog hloov mus rau hauv nws daim ntawv active triphosphate los ntawm ib tug series ntawm phosphorylation kauj ruam uas yog sped los ntawm cellular kinases. Qhov kev ua haujlwm metabolic no yog qhov tseem ceeb hauv kev ua haujlwm zoo li cas cov tshuaj tiv thaiv kab mob. Lub molecule yuav tsum muaj peev xwm sib tw nrogGS-441524 hmoovthiab ntuj adenosine rau kinase kev txiav txim thiab tsim kom muaj siab txaus hauv cov hlwb.GS-441524 hmoov muaj cov txiaj ntsig zoo metabolic uas pab nws nkag mus rau hauv cov hlwb thiab tau muab faib rau hauv cov ntaub so ntswg, raws li kev tshawb fawb. Vim tias cov molecule ruaj khov npaum li cas, nws tuaj yeem nyob ntawm qib kho mob hauv cov kab mob kis los ntawm ntau yam kab mob sib kis. Qhov no ua rau tus kab mob sib kis los ntawm kev siv cov tshuaj tiv thaiv kab mob tsis tu ncua.

GS-441524 Hmoov rau cuam tshuam RNA Synthesis hauv Coronaviruses

 

Targeting Coronavirus RNA-Dependent RNA Polymerase

Coronaviruses muaj txoj hauv kev tshwj xeeb ntawm kev rov ua dua uas yog ua raws li kev txuag RdRp enzyme complex. Cov polymerase no muaj qee qhov zoo ntawm molecular uas ua rau nws yooj yim rau nucleoside analogs kom tsis txhob ua haujlwm. GS-441524 hmoov lub hom phiaj no enzymatic complex tshwj xeeb, siv nws cov txheej txheem catalytic ua yuam kev hauv kev tsim tawm. Tus kab mob coronavirus RdRp ua haujlwm los ntawm kev siv ob -cov txheej txheem hlau-ion catalytic uas ua rau nws yooj yim dua rau nucleotides los koom nrog cov saw RNA loj hlob.

 

Lub triphosphate version ntawm GS-441524 hmoov yog ze heev rau ntuj ATP, yog li nws tuaj yeem nkag mus rau hauv qhov chaw nquag ntawm cov enzyme thiab koom nrog hauv lub voj voog catalytic. Thaum cov enzyme cov ntaub ntawv pov thawj tuaj yeem kho qee qhov yuam kev replication, lawv tsis zoo heev los nrhiav thiab tshem tawm cov ntawv ntxiv.

Kev cuam tshuam rau Viral Genome Integrity

Thaum GS-441524 hmoov koom nrog tus kab mob RNA, nws hloov cov qauv hauv txoj hauv kev uas cuam tshuam rau cov xwm txheej rov ua dua ntxiv hauv kab.

 

Vim tias cov kev hloov pauv no, qhov kev rov ua dua tshiab tom ntej yuav tsis raug, uas ua rau cov noob caj noob ces ua haujlwm tsis zoo. Thaum cov kev ua yuam kev no ntxiv lawm, lawv ua rau cov kab mob progeny tsawg tuaj yeem tua lwm tus thiab txo qis kev noj qab haus huv ntawm tus kab mob. Cov kws tshawb fawb uas tau saib mus rau hauv yuav ua li cas tus kabmob coronaviruses rov ua dua tau pom tias GS-441524 hmoov ua rau cov kab mob qeeb zuj zus. Thaum cov khoom xyaw ntxiv rau cov kab mob, lawv ua kom tsawg dua cov kab mob. Cov uas tau tso tawm feem ntau muaj qhov tsis zoo ntawm caj ces uas ua rau nws nyuaj rau lawv los tawm tsam cov tswv tsev tshiab.

GS-441524 Powder Stop RNA Chain Elongation nyob rau hauv Kab Mob Cell?

Delayed Chain Termination Mechanism

GS-441524 hmoov ua rau ncua sij hawm txiav tawm, uas txawv ntawm lwm cov saw terminators uas nres polymerization tam sim ntawd. Thaum nws tau muab tso rau hauv tus kab mob RNA strand, daim ntawv luam cia ob peb ntxiv nucleotides ntxiv ua ntej tso tseg replication. Qhov kev cuam tshuam no tshwm sim tom qab vim muaj kev hloov me me hauv cov qauv ntawm RNA qaum qaum uas maj mam nres cov polymerase los ntawm kev mus rau pem hauv ntej. Cov piam thaj hloov pauv ntawm GS-441524 hmoov ua rau muaj kev hloov me me hauv cov duab ntawm RNA helix, uas yog qhov ua rau qhov kev ncua qeeb. Raws li cov polymerase sim txuas ntxiv cov saw hlau dhau los ntawm cov khoom siv analog, cov kev ua yuam kev no zuj zus tuaj.

Qee lub sij hawm, cov kev txwv geometric tau nruj txaus ua rau cov polymerase-RNA complex tsis ruaj khov,GS-441524 hmoovuas ua rau nws tawg sai heev thiab tawm genome synthesis tsis tiav.

Kinetic Barriers rau Elongation

Kawm txog kev ua haujlwm enzymatic ntawm tus mob coronavirus RdRp tau qhia tias GS-441524 hmoov thaiv kev txav ntawm elongation li cas.

Thaum daim ntawv theej yog nyob rau hauv RNA template, nws slows down qhov ntxiv ntawm nucleotides rau qhov chaw ntxiv downstream. Txhua zaus cov polymerase sim nyeem los ntawm cov cheeb tsam nrog ntau cov analogs sib xyaw, qhov kev poob qis no tau muaj zog dua. Cov teeb meem kinetic no muaj kev sib koom ua ke ua rau nws nyuaj rau cov kab mob ua rau RNA hauv cov hlwb uas cuam tshuam. Sib piv cov nqi ntawm cov kab mob RNA hauv cov hlwb uas tau kho thiab cov hlwb uas tsis tau kho qhia tau hais tias ob hom genomic thiab subgenomic RNA yog qis dua. Qhov no qhia tau hais tias cov tshuaj muaj kev cuam tshuam dav rau cov txheej txheem sau thiab rov ua dua ntawm cov kab mob.

Yuav ua li cas GS-441524 Powder tiv thaiv Viral Genome Replication Nthuav zoo

 

Inhibition ntawm Positive thiab Negative Strand Synthesis

Qhov zoo -sensitive thiab negative-sension RNA strands yog tsim thaum lub sij hawm RNA tus kab mob tsim. Cov strands no muaj cov haujlwm sib txawv hauv cov kab mob viral. Raws li qhov tshwm sim ntawm lub hom phiaj ntawm RdRp enzyme uas ua rau ob hom strands, GS-441524 hmoov nres cov khoom ntawm lawv. Cov tshuaj tiv thaiv kab mob no tau nce ntxiv los ntawm nws lub peev xwm los thaiv ob txoj hauv kev sib txawv.Ib kauj ruam tseem ceeb heev hauv cov kab mob rov ua dua yog ua qhov tsis zoo - cov qauv strand los ntawm qhov zoo-strand DNA.

 

Thaum GS-441524 hmoov ntxiv rau lub sijhawm no, nws ua rau cov khoom tsis zoo -strand templates uas tom qab ntawd ua rau cov xeeb ntxwv tsis zoo-strand. Qhov kev sib kis ntawm qhov yuam kev no ua rau qhov sib xyaw ua ke thaiv cov nyhuv muaj zog dua ntau qhov kev tsim tawm.

Txo hauv Subgenomic RNA Production

Coronaviruses thiab lwm yam kab mob RNA uas txuas nrog lawv ua cov txheej txheem subgenomic RNAs uas code rau cov qauv thiab cov khoom siv protein. Txhawm rau ua cov kab mob subgenomic no, RdRp enzyme yuav tsum ua tsis tu ncua.

 

Qhov no txhais tau tias nws yuav tsum dhia ntawm cov cheeb tsam template kom ua rau cov qauv sib txawv tshwj xeeb. Qhov kev hloov pauv nyuaj no yog messed los ntawm GS-441524 hmoov, uas txo qis kev ua haujlwm ntawm polymerase thiab qhov tseeb ntawm template swapping. Cov qib subgenomic RNA tau ntsuas hauv cov kab mob uas tau kho nrog GS-441524 hmoov thiab pom cov tee loj hauv tag nrho cov kab mob gene qhia cov khoom. Qhov kev thaiv tag nrho ntawm viral transcription nres qhov tsim cov txheej txheem tseem ceeb uas xav tau rau kev sib dhos virion. Qhov no ua rau nws nyuaj rau kis rau lwm tus hauv txoj kev uas tsis yog txwv tsis pub genome replication ncaj qha.

GS-441524 Hmoov thiab Molecular Science Tom Qab RNA Virus Txhaum Cai

Kev cuam tshuam nrog Viral Polymerase Active Site

Siv X-ray crystallography thiab cryo-electron imaging los ua cov kev tshawb fawb zoo heev,GS-441524 hmoovtau muab ntau yam ntaub ntawv rau peb txog yuav ua li cas GS-441524 hmoov ua haujlwm nrog cov kab mob polymerase enzymes. Cov kev tshawb fawb qhia tau hais tias cov compound daim ntawv triphosphate khi rau lub hnab tshos nucleotide-binding ntawm enzyme. Tom qab ntawd nws tsim cov kev cuam tshuam tseem ceeb nrog kev txuag cov amino acid residues uas tswj ob lub hlau ions xav tau rau catalysis. Cov duab ntawm GS-441524 hmoov lub triphosphate ua rau nws hloov pauv nucleobase ntsej muag nyob rau hauv ib txoj kev uas zoo li ntuj adenosine.

Qhov no cia cov polymerase paub tias nws yog ib qho substrate tiag tiag. Cov kauj ruam tom ntej yog kev koom ua ke uas siv ob qho tib si -hlau- ion mechanism. Qhov no tsim ib qho kev sib txuas ntawm phosphodiester ntawm tus tshiab version thiab cov saw RNA loj hlob.

Conformational Hloov hauv Polymerase-RNA Complex

Tom qab GS-441524 hmoov ntxiv, lub polymerase-RNA complex mus los ntawm kev hloov me me ntawm nws cov duab. Cov kev hloov pauv rau cov qauv no cuam tshuam rau qhov chaw seem ntawm qhov chaw nyob thiab yuav ua li cas RNA strand tshiab yog lined. Cov qauv molecular dynamics tau pom tias cov kev hloov pauv no tshwm sim ntau dua li cov polymerase sim ua kom cov saw hlau ntev dua li cov ntawv luam uas twb muaj lawm.

Thaum kawg, cov kab mob sib kis tau tshwm sim los ntawm GS-441524 hmoov yog ntau dua li lub zog ruaj khov muab los ntawm polymerase-RNA kev sib cuag, uas ua rau lub complex sib cais. Cov txheej txheem no txawv ntawm qhov kev txiav tawm sai sai los ntawm obligate chain terminators. Nws muaj ib tug tshwj xeeb pharmacological profile uas tej zaum yuav zoo dua nyob rau hauv cov nqe lus ntawm kev tiv thaiv lub tsev thiab antiviral zoo.

Biochemical Validation Los ntawm Enzymatic Assay

Siv cov ntshiab viral polymerases nyob rau hauv vitro biochemical kuaj tau muab cov naj npawb rau GS-441524 hmoov cov kev ua tau zoo inhibitory. Cov kev tshawb fawb no qhia tau hais tias cov molecule muaj zog tiv thaiv kab mob nyob rau theem molecular, nrog rau IC50 qhov tseem ceeb nyob rau hauv qis micromolar ntau yam rau thaiv tus mob coronavirus RdRp.

Cov molecule ua haujlwm raws li kev sib tw inhibitor tiv thaiv ntuj ATP, uas haum nrog nws ua haujlwm li nucleoside analog, raws li kev tshawb fawb enzyme dynamics. Cov yam ntxwv molecular uas txiav txim siab GS-441524 hmoov susceptibility tau coj mus rau lub teeb los ntawm kev sib piv cov kev tawm tsam ntawm cov kab mob sib txawv polymerases. Polymerases nrog stricter substrate selectivity yog qhov zoo dua ntawm kev paub txog cov analog thiab tsis hnov ​​​​mob rau nws, thaum cov uas tsis tshua muaj kev xaiv nruj dua yuav hnov ​​​​mob. Cov kev sib txuas ntawm cov qauv thiab kev nqis tes ua pab cov kws tshawb fawb ua cov nucleoside analogs uas muaj txiaj ntsig zoo rau cov kab mob thiab muaj ntau yam cuam tshuam.

Xaus

Cov tshuaj chemical uasGS-441524 hmoovnres qhov kev rov ua dua ntawm cov kab mob RNA qhia tias kev sib cuam tshuam ntawm cov tshuaj tiv thaiv kab mob thiab cov cuab yeej siv cov kab mob li cas los luam lawv tus kheej. Qhov sib xyaw no qhia tau hais tias cov lus cog tseg ntawm nucleoside analogs hauv kev kho tshuaj tiv thaiv kab mob vim tias nws muaj cov qauv zoo ib yam li cov nucleotides ntuj, ncua kev cuam tshuam cov saw txuas, thiab kev nyiam rau kev tsom mus rau cov kab mob polymerases. Cov kws tshawb fawb ua haujlwm ntawm nthwv dej tom ntej ntawm cov tshuaj tiv thaiv kab mob thiab cov tuam txhab tshuaj uas sim daws cov kab mob tshiab tuaj yeem kawm tau ntau yam los ntawm kev nkag siab txog cov txheej txheem no. Cov molecule no yog ib tug haib antiviral riam phom vim hais tias nws muaj peev xwm nres ntau theem ntawm tus kab mob genome replication thaum tseem tab tom xaiv rau tus kab mob enzymes thiab tsis yog tib neeg enzymes. Raws li kev tshawb fawb txog virology thiab tshuaj txuas ntxiv mus, cov tshuaj xws li GS-441524 hmoov qhia tau cog lus tias yog txoj hauv kev los tiv thaiv tus kab mob RNA. Muaj lub hauv paus kev tshawb fawb txog nws ua haujlwm li cas, uas txhawb nqa nws txoj kev loj hlob ntxiv thiab siv los daws cov teeb meem loj RNA ntsig txog kev noj qab haus huv hauv cov tsiaj.

FAQ

Koom tes nrog BLOOM TECH raws li Koj Trusted GS-441524 Powder Supplier

BLOOM TECH sawv ua koj tus khub txhim khu kev qha rau siab - zooGS-441524 hmoovcov kev daws teeb meem, txhawb nqa los ntawm ntau dua 12 xyoos ntawm kev ua tau zoo hauv cov organic synthesis thiab tshuaj intermediates. Peb GMP-cov chaw tsim khoom tau ntawv pov thawj ua tau raws li US, EU, JP, thiab CFDA cov qauv, ua kom txhua pawg ntawm GS-441524 hmoov ua tau raws li cov lus qhia nruj zoo nrog rau qib purity ntau dua lossis sib npaug li 98%. Raws li cov neeg tsim khoom tsim nyog rau 24 lub tuam txhab tshuaj thoob ntiaj teb, peb muab cov ntaub ntawv txheeb xyuas dav dav (HPLC, MS), kev txhawb nqa kev tswj hwm, thiab cov kev xaiv muaj peev xwm ua tau raws li koj qhov kev tshawb fawb lossis kev lag luam xav tau. Peb triple- txheej txheej tswj kev ua tau zoo tau lees paub cov khoom ncaj ncees, thaum peb tus qauv tus nqi pob tshab thiab ib qho - nres kev pabcuam platform ua kom koj cov txheej txheem yuav khoom. Txawm hais tias koj xav tau kev tshawb fawb-qib ntau lossis kev txhawb nqa kev tsim khoom ntau, peb pab neeg ua haujlwm xa cov sijhawm ua haujlwm raug, cov ntaub ntawv ntxaws txog kev lis kev cai, thiab kev pabcuam kev teb.

Hu rau peb pab neeg hnub no ntawmSales@bloomtechz.comlos tham txog koj GS-441524 hmoov yuav tsum tau thiab nrhiav tau li cas BLOOM TECH cov kev txawj ntse nyob rau hauv cov organic chemical synthesis yuav ua rau kom koj cov tshuaj tiv thaiv kab mob kev tshawb fawb thiab kev loj hlob pib.

Cov ntaub ntawv

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2. Pruijssers, AJ, George, AS, Schäfer, A., Leist, SR, Gralinksi, LE, Dinnon, KH, Yount, BL, Agostini, ML, Stevens, LJ, Chappell, JD, Lu, X., Hughes, TM, Gully, K., Martinez, DR, Brown, AJ, Brown, K. V., Pitts, J., Ma, B., Babusis, D., Murakami, E., Clarke, MO, Mackman, RL, Spahn, JE, Palmiotti, C., Siegel, D., Ray, AS, Bannister, R., Schulz, R., Chun, K., & Baric, 2. Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in nas. Cell Reports, 32(3), 107940.

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

4. Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L., Wang, T., Sun, Q., Ming, Z., Zhang, L., Ge, J., Zheng, L., Zhang, Y., Wang, H., Zhu, Y., Zhu, C., Hu, T. J., Yang, H., Liu, Z., Xu, W., Guddat, LW, Wang, Q., Lou, Z., & Rao, Z. (2020). Cov qauv ntawm RNA- nyob ntawm RNA polymerase los ntawm tus kab mob COVID-19. Science, 368(6492), 779-782.

5. Agostini, ML, Andres, EL, Sims, AC, Graham, RL, Sheahan, TP, Lu, X., Smith, EC, Case, JB, Feng, JY, Jordan, R., Ray, AS, Cihlar, T., Siegel, D., Mackman, RL, Clarke, RS, 2. Coronavirus cuam tshuam rau cov tshuaj tiv thaiv kab mob remdesivir (GS-5734) yog kho los ntawm tus kab mob polymerase thiab cov ntawv pov thawj exoribonuclease. mBio, 9(2), e00221-18.

6. Warren, TK, Jordan, R., Lo, MK, Ray, AS, Mackman, RL, Soloveva, V., Siegel, D., Perron, M., Bannister, R., Hui, HC, Larson, N., Strickley, R., Wells, J., Stuthman, Garne, KS, Van Tong, Shurtleff, AC, Retterer, CJ, Gharaibeh, D., Zamani, R., Kenny, T., Eaton, BP, Grimes, E., Welch, LS, Gomba, L., Wilhelmsen, CL, Nichols, DK, Nuss, JE, Nagle, ER, Kugelman, J. Neville, S., Carra, E., Clarke, MO, Zhang, L., Lew, W., Ross, B., Wang, Q., Chun, K., Wolfe, L., Babusis, D., Park, Y., Stray, KM, Trancheva, I., Feng, JY, Barauskas, O., Lin Xu, M. McMullan, LK, Chen, SS, Fearns, R., Swaminathan, S., Mayers, DL, Spiropoulou, CF, Lee, WA, Nichol, ST, Cihlar, T., & Bavari, S. (2016). Kev kho tau zoo ntawm cov me me molecule GS-5734 tiv thaiv tus kab mob Ebola hauv rhesus liab. Xwm, 531(7594), 381-385.