Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm n(4)-hydroxycytidine hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo n(4)-hydroxycytidine muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
N(4)-hydroxycytidine(Engagliflozin, -D-N⁴-hydroxycytidine, code npe EIDD-1931) yog ib qho hluavtaws pyrimidine ribonucleoside analog. Nws ua haujlwm raws li lub hauv paus tseem ceeb metabolite ntawm molnupiravir, dav -spectrum antiviral agent, nrog CAS Registry Number 3258-02-4. Nws cov qauv tshuaj muaj qhov zoo sib xws rau ntuj cytidine, txawv tsuas yog los ntawm kev hloov kho hydroxyl txuas nrog cov amino pawg ntawm 4-txoj hauj lwm ntawm lub nplhaib pyrimidine; Qhov kev ua haujlwm tshwj xeeb no txhawb nqa nws txoj haujlwm tiv thaiv kab mob. Nws nthuav tawm cytotoxicity tsis txaus ntseeg, dej solubility zoo heev thiab cellular permeability, thiab tawm tsam cov kab mob RNA dav dav. Tam sim no, nws ua tsis tau tsuas yog Engagliflozin ua ib qho tseem ceeb ntawm cov tshuaj tiv thaiv kev tshawb pom tshiab, tab sis kuj yog ib qho tseem ceeb molecular cuab yeej rau kev tshawb fawb ntawm tus kab mob-mediated replication mechanisms thiab antiviral pharmacology.
Peb Cov Khoom Muag Khoom
N(4)-hydroxycytidineCOA
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| Certificate of Analysis | ||
| Compound npe | N(4)-hydroxycytidine | |
| Qib | Pharmaceutical qib | |
| CAS Nr. | 3258-02-4 | |
| Ntau | 56g | |
| Ntim txheem | PE hnab + Al foil hnab | |
| Chaw tsim tshuaj paus | Shaanxi BLOOM TECH Co., Ltd | |
| Ntau No. | 202601090056 | |
| MFG | Peb 9, 2026 | |
| EXP | Peb 8, 2029 | |
| Qauv |
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| Yam khoom | Enterprise txheem | Kev txheeb xyuas qhov tshwm sim |
| Qhov tshwm sim | Dawb los yog yuav luag dawb hmoov | Ua raws |
| Cov ntsiab lus dej | Tsawg dua lossis sib npaug li 5.0% | 0.45% |
| Poob rau ziab | Tsawg dua lossis sib npaug li 1.0% | 0.19% |
| Hnyav Hlau | Pb Tsawg dua lossis sib npaug li 0.5ppm | N.D. |
| Tsawg dua lossis sib npaug li 0.5ppm | N.D. | |
| Hg Tsawg dua lossis sib npaug li 0.5ppm | N.D. | |
| Cd Tsawg dua lossis sib npaug li 0.5ppm | N.D. | |
| Purity (HPLC) | Ntau dua lossis sib npaug li 99.0% | 99.98% |
| Ib qho impurity | <0.8% | 0.57% |
| Tag nrho microbial suav | Tsawg dua lossis sib npaug li 750cfu / g | 600 |
| E. Coli | Tsawg dua lossis sib npaug li 2MPN / g | N.D. |
| Salmonella | N.D. | N.D. |
| Ethanol (los ntawm GC) | Tsawg dua lossis sib npaug li 5000ppm | 750ppm ua |
| Cia | Khaws rau hauv qhov chaw kaw, tsaus, thiab qhuav hauv qab -20 degree | |
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| Tshuaj Formula | C9H13N3O6 |
| Exact Mass | 259.08 |
| Molecular Luj | 259.22 |
| m/z | 259.08 (100.0%), 260.08 (9.7%), 261.08 (1.2%) |
| Elemental Analysis | C, 41.70; H, 5.06; N, 16.21; O, 37.03 |
Mechanism ntawm Action
Intracellular Activation thiab Metabolic Pathway
Qhov yuav tsum tau ua ua ntej rauN(4)-hydroxycytidinetxhawm rau ua kom muaj cov tshuaj tiv thaiv kab mob nyob hauv cov txheej txheem phosphorylation ua kom kho tau los ntawm tus tswv tsev cellular metabolic machinery. Dawb engagliflozin niam txiv molecule qhia tias tsis muaj cov tshuaj tiv thaiv kab mob thiab ua haujlwm tsuas yog ib qho tshuaj tshwj xeeb uas tsis tuaj yeem cuam tshuam ncaj qha rau tus kab mob- kho dua tshiab. Tom qab nkag mus rau tus tswv cytoplasm los ntawm kev sib kis tsis zoo ua ke nrog cov nucleoside transporter proteins ntawm cov cell membranes, engagliflozin tam sim ntawd dhau ntau -theem phosphorylation hloov kho. Cov txheej txheem ua kom no tso siab rau tag nrho cov tib neeg endogenous nucleoside kinases thiab phosphokinases, ywj siab ntawm tus kab mob-cov proteins koom nrog koom tes los ntawm cov kab mob.
Cov cuab yeej no ua rau engagliflozin hloov mus rau intracellular microenvironment ntawm cov cell kis los ntawm tag nrho cov kab mob RNA, ua lub hauv paus tseem ceeb rau nws qhov dav -spectrum antiviral profile. Ua ntej, tus tswv tsev thymidine kinase thiab uridine kinase catalyze tus thawj monophosphorylation ntawm { engaglifloz} mus rau engagliflozin monophosphate (NHC-MP), ua kom tiav qhov kev ua haujlwm ntawm molecular ua ntej. Tom qab tas li catalysis los ntawm cytoplasmic phosphotransferases converts NHC-MP sequentially mus rau hauv diphosphate intermediate (NHC-DP), thiab thaum kawg yields biologically active N⁴-hydroxycytidine triphosphate (NHC-TP).
NHC-TP qhia txog homologous spatial conformation nrog endogenous tib neeg cytidine triphosphate, nrog rau qhov ntev ntawm molecular, tsub nqi tis thiab substrate binding zog zoo sib xws rau cov chaw nquag ntawm tus kab mob- koom nrog RNA-dependent RNA polymerase (RdRp).
Nws tuaj yeem raug lees paub thiab raug ntes los ntawm RdRp ntawm ntau yam kab mob RNA thiab suav nrog ua ib qho kev tsis txaus ntseeg rau hauv cov kab mob nascent -txoj kev RNA strands.Notably, NHC-TP muaj kev sib raug zoo tsis tshua muaj rau cov tswv tsev cellular DNA polymerases thiab canonical RNA polymerases, thiab NW nyuam qhuav hloov pauv hauv tib neeg.
Nws tshwj xeeb yog tsom rau tus kab mob- koom nrog RNA replication systems, uas hauv paus tsis txhob cytotoxicity thiab cuam tshuam rau tus tswv tsev metabolic homeostasis thiab nteg lub hauv paus zoo rau kev siv tshuaj.
Mechanism of virus-sociated RNA Incorporation thiab Mismatch Mutagenesis
Thaum lub sij hawm elongation ntawm RNA strands catalyzed los ntawm tus kab mob -koom RdRp, qhib NHC -TP yog randomly integrated rau cov tshiab synthesized tus kab mob - koom nrog genomic RNA, cuam tshuam canonical puag -pairing txoj cai thiab pib genesismatch} tus kab mob genesismatch. genome.
Cov pab pawg hydroxyl ntawm 4- txoj hauj lwm ntawm lub nplhaib pyrimidine ntawm engagliflozin ua raws li nws txoj haujlwm tseem ceeb moiety, ua rau keto dynamic keto-enol tautomerization thiab endowing cov molecule nrog dual puag-mimicking yam ntxwv: lub keto tautomer mimics ntuj cytidine hauv paus thiab cov ntaub ntawv g. lub enol tautomer ua raws li uridine thiab ruaj khov khi rau adenine.
Cov cuab yeej tshwj xeeb tautomeric no ua rau engagliflozin embedded nyob rau hauv tus kab mob -txoj kev RNA strands ib tug mutagenic hotspot rau genome replication, tsis tu ncua ua rau hauv paus-pairing teeb meem thaum lub sij hawm tom qab tus kab mob -txoj kev loj hlob thiab kis.
Hauv thawj kab ntawm tus kab mob-kev hloov pauv hloov pauv, sib koom ua ke engagliflozin hloov cytidine nyob rau hauv RNA strands yam tsis tau txiav RNA elongation ncaj qha, ua rau muaj kev zais ntau ntawm kev hloov pauv. Hauv qhov thib ob thiab tom ntej ntawm kev rov ua dua tshiab, RNA cov qauv uas muaj engagliflozin txhawb nqa qhov tsis sib xws, ua rau muaj kev sib koom ua ke ntawm adenine thiab guanine rau hauv cov noob caj noob ces thiab tsim ntau cov kev hloov pauv ntawm kev hloov pauv ntawm C → U thiab G→ A. Cov kev hloov pauv no tsis muaj cov kab mob sib kis tag nrho - kev cuam tshuam los ntawm cov kab mob sib kis. genome, npog cov txheej txheem cov noob caj noob ces, hloov cov noob, tswj cov noob thiab lwm thaj chaw es tsis txwv rau ib qho kev ua haujlwm.
Qhov no ua rau muaj kev cuam tshuam kev sib raug zoo ntawm coding thiab genetic stability ntawm tus kab mob -txoj kev genomes thiab hauv paus cuam tshuam tus kab mob ib txwm muaj- cuam tshuam kev loj hlob. Piv nrog rau cov tshuaj inducing ib leeg - site mutations, engagliflozin generates ntau dua mutation ceev thiab dav dav. Cov kab mob tsis tuaj yeem them nyiaj rau genomic defects los ntawm kev kho cov noob hauv zos, ua rau muaj kev cuam tshuam ntau dua mutagenic.
Viral Error Catastrophe Effect
genome-ntau qhov kev hloov pauv uas tshwm sim los ntawm engagliflozin sib sau ua ke tsis tu ncua thaum kis kab mob sib kis- cuam tshuam nrog.
Thaum qhov kev hloov pauv ntau dhau ntawm tus kab mob- koom nrog genome qhov kev ua yuam kev ua siab ntev, tus kab mob classic- cuam tshuam kev ua yuam kev raug kev puas tsuaj tshwm sim, thaum kawg tshem tawm tus kab mob- koom nrog kev muaj peev xwm rov ua dua.RNA cov kab mob feem ntau muaj cov txheej txheem rov ua dua tshiab thiab tsis muaj kev cuam tshuam. Lawv RdRp tsis muaj 3'-5' exonuclease proofreading kev ua thiab tsis tuaj yeem paub lossis kho qhov tsis sib haum xeeb vim yogN(4)-hydroxycytidine, ua rau muaj kev hloov pauv loj ntawm novo hauv txhua lub voj voog rov ua dua.
Raws li kev hla dhau mus, lub luag haujlwm hloov pauv ntawm tus kab mob- cov kab mob sib txuas tau nce exponentially nrog kev txuas ntxiv ntawm kev tsis lees paub, tsis muaj tseeb thiab hloov pauv hloov pauv, maj mam rhuav tshem genomic functionality thiab kev ncaj ncees.
Thaum kev hloov pauv hloov mus txog qhov tseem ceeb, tus kab mob tseem ceeb - cuam tshuam cov haujlwm tseem ceeb tau raug tshem tawm tag nrho. Ntawm ib sab, cov protein ua haujlwm tseem ceeb uas tau txais los ntawm cov kab mob (RdRp, helicase, replication cofactors, thiab lwm yam) raug cuam tshuam cov amino acid ib ntus thiab folding txawv txav vim kev hloov pauv, poob catalytic kev ua haujlwm rau tus kab mob - koom nrog genome replication thiab thaiv cov kab mob progeny synthesis{4}. Ntawm qhov tod tes, kev puas tsuaj rau tus kab mob-cov hnab ntawv sib koom nrog cov proteins thiab nucleocapsid proteins tiv thaiv tus kab mob-cov khoom sib txuas ua ke, budding thiab maturation, tsim kom muaj ntau ntawm cov kab mob tsis zoo- cov khoom sib txuas uas tsis muaj peev xwm kis tau.
Cov virions tsis zoo no tsis tuaj yeem kis tus tswv tsev tshiab; lub caij no, lawv nthuav tawm cov kab mob tiv thaiv kab mob - txuam nrog antigenic epitopes thiab tau nkag tau yooj yim dua thiab raug tshem tawm los ntawm tus tswv macrophages thiab lymphocytes. Tsis tas li ntawd, genome- dav siab - thauj cov kev hloov pauv tag nrho thaiv kev hloov pauv hloov pauv thiab kev tiv thaiv kev xaiv ntawm cov kab mob, tiv thaiv kev tshwm sim ntawm cov tshuaj tiv thaiv los ntawm ib qho - kis tus kab mob- cuam tshuam kev hloov pauv. Qhov no hais txog qhov kev txwv tseem ceeb ntawm kev tiv thaiv tsis tu ncua cuam tshuam nrog cov tshuaj tiv thaiv kab mob ib txwm muaj thiab ua kom muaj kev tawm tsam thiab tshem tawm cov kab mob.
Mechanism Underpinning Broad -Spectrum Antiviral Activity
Qhov dav -spectrum antiviral kev ua haujlwm ntawm engagliflozin pib los ntawm nws qhov tshwj xeeb thoob ntiaj teb genome mutagenesis inhibition mechanism, uas txawv ntawm cov tshuaj ib txwm tsom rau ib tus kab mob -cov proteins sib txuas.Nws muaj txiaj ntsig zoo tshaj plaws rau qhov zoo tshaj plaws - hnov tib yam - tso tseg RNA viruses, alphaviruses, thiab lwm yam kab mob siab, pathogenic RNA viruses.Proliferation of all RNA viruses relies on RdRp-mediated virus-sociated genome replication and lacks base proofreading and repair mechanisms. Qhov kev sib koom ua ke no tsim kom muaj lub hom phiaj tiv thaiv kab mob thoob ntiaj teb rau engagliflozin, ua kom dav -spectrum ua tau zoo yam tsis muaj kev hloov kho rau cov kab mob sib txawv.
Rau cov kab mob coronaviruses suav nrog SARS-CoV-2 thiab MERS-CoV, engagliflozin zoo inhibits qus- hom kab mob xws li Delta thiab Omicron. Txawm hais tias cov kab mob sib kis kab mob sib kis sib kis los ntawm tus kab mob - cuam tshuam kev tiv thaiv kab mob, cov tshuab luam ntawv tseem ceeb tseem tsis tau hloov pauv thiab tsis tuaj yeem khiav tawm NHC -induced genomic mutagenesis. engagliflozin tseem suppresses replication thiab kis ntawm cov kab mob RNA uas muaj kev pheej hmoo siab xws li kab mob khaub thuas A, chikungunya virus thiab Venezuelan equine encephalitis tus kab mob los ntawm kev sib hloov genomic. Tsis tas li ntawd, engagliflozin qhia tau zoo heev host compatibility thiab tsawg toxicity.
Nws cov txheej txheem ua kom muaj zog thiab ua haujlwm tau xaiv hom kab mob - koom nrog RNA replication yam tsis muaj kev cuam tshuam nrog tus tswv DNA replication, gene transcription thiab ib txwm protein synthesis, conferring tsawg toxicity rau noj qab haus huv cov ntaub so ntswg. Thaum muaj tus kab mob-kab mob sib kis, engagliflozin sai txo tus kab mob- txuam nrog load hauv vivo, alleviates cytolytic kev puas tsuaj los ntawm cov kab mob, suppresses tus kab mob- ua rau ntau dhau inflammatory teb thiab apoptosis, thiab muab sijhawm txaus rau kev ua kom lub cev tsis muaj zog thiab tiv thaiv kab mob. Qhov no synergistic nyhuv ntawm pharmacological inhibition thiab tiv thaiv kab mob clearance ho txhim kho antiviral kev cuam tshuam tshwm sim.
Tam sim no, cov khoom siv hluav taws xob tseem ceeb rau cov khoom lag luam ntiav cov uridine pheej yig raws li cov khoom siv pib los ntawm plaub- cov kauj ruam hloov kho cov tshuaj tiv thaiv, uas muaj cov haujlwm yooj yim thiab cov khoom siab purity.
Cov txheej txheem tseem ceeb suav nrog kev tiv thaiv hydroxyl, ua kom C4 qhov chaw ntawm lub nplhaib pyrimidine, kev hloov nucleophilic los ntawm hydroxylamine thiab acidic deprotection.
Silyl reagents tiv thaiv ribosyl hydroxyl pawg kom tsis txhob muaj kev cuam tshuam sab; sulfonylation activates lub hom phiaj site los qhia hydroxyamino pawg. Tom qab deprotection, ua ke nrog recrystallization thiab kem chromatography purification, affords cov khoom kawg.
Cov txheej txheem hluavtaws no ua haujlwm nyob rau hauv cov mob me me uas muaj zog regioselectivity thiab ruaj khov yields. Lub purity ntawm cov khoom tiav tuaj yeem tshaj 98%, haum rau kev npaj hauv chav kuaj thiab me me - nplai kev lag luam.
Cov ntaub ntawv
- BenchChem. Ib Daim Ntawv Qhia Hauv -Txoj Kev Taw Qhia Qhov tob rau -D-N⁴-hydroxycytidine (EIDD-1931)[R/OL].
- Urakova N, et al . -d-N⁴-hydroxycytidine yog ib qho muaj zog tiv thaiv-alphavirus compound uas ua rau muaj kev hloov pauv siab hauv cov kab mob genome[J]. Phau ntawv Journal of Virology, 2018, 92(24):e01651-17.
- InvivoChem. Technical Specification thiab Pharmacological Activity of EIDD-1931 ( -d-N⁴-hydroxycytidine; NHC)[EB/OL].
- PMC. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis[J]. 2021, 15(10):e0078921.
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