Home Microbiology Reverse Transcriptase Hämmare Zidovudine

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Zidovudine Reverse Transcriptase Hämmare

Kat.nr.: S2579

Zidovudine (ZDV, Azidothymidine, NSC 602670) är en nukleosidanalog reverse transcriptase-hämmare som används för att behandla HIV. Denna förening kan minska HDR-effektiviteten och minska CRISPR-medierade sekvensspecifika genom-knockin-händelser samtidigt som knockouteffektiviteten ökar.
Zidovudine Reverse Transcriptase Hämmare Chemical Structure

Kemisk struktur

Molekylvikt: 267.24

Hoppa till

Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.90%
99.90

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer Analystyp Koncentration Inkubationstid Formulering Aktivitetsbeskrivning PMID
human C8166 cells Function assay Antiviral activity against Human immunodeficiency virus 1 infected in human C8166 cells assessed as inhibition of virus-induced cytopathic effect, EC50=4e-06 μM
PBMC Function assay 1 μM Antiviral activity against HIV1 TEKI replication in PBMC at 1 uM, IC50=0.00014 μM
human H9 cells Function assay 6 days Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 6.25 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.3 nM
AA5 cells Function assay Antiviral activity against of Human immunodeficiency virus 1 3B infected in AA5 cells infected with 1.56 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.3 nM
CEM cells Function assay Concentration of the drug resulting in 50% reduction of the viral cytopathic effect against HIV-1 replication in CEM cells, EC50=0.32 nM
MT4 cells Function assay 4 days Antiviral activity against HIV1 3B assessed as inhibition of virus-induced cytopathogenicity in MT4 cells after 4 days by MTT assay, EC50=0.7 nM
human MT2 cells Function assay 1 h Antiviral activity against HIV1 subtype B-3B infected in 1 hr-pretreated human MT2 cells assessed as inhibition of multicycle replication measured on day 5 postinfection by RT SPA, EC50=1.2 nM
C8166 cells Function assay Inhibition of HIV1-3B replication in C8166 cells, EC50=1.9 nM
CEM-SS cell Function assay Inhibitory activity against the HIV-1-induced cytopathic effect in CEM-SS cell line, IC50=0.002 μM
PBLs Function assay Antiviral activity against subtype isolate G strain in PBLs (peripheral blood lymphocytes), IC50=0.002 μM
human lymphocyte CEM/0 cell line Function assay Anti HIV-1 activity in human lymphocyte CEM/0 cell line, EC50=0.003 μM
Jurkat cell Function assay Inhibitory concentration against HIV-1 infected Jurkat cell lines, IC50=0.01 μM
human H9 cells Cytotoxicity assay 6 days Cytotoxicity against human H9 cells after 6 days by MTT assay, EC50=0.01 μM
C3H/3T3 cells Function assay Concentration of compound required to inhibit HIV-1 induced cytopathogenicity of MSV-induced transformation of C3H/3T3 cells by 50%, EC50=0.02 μM
U937 cells Function assay Effective concentration required for antiviral activity against Macrophage cell line of U937 cells of Human by XTT assay, EC50=0.03 μM
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt 267.24 Formel

C10H13N5O4

 Lagring (från mottagningsdatumet)
CAS-nr 30516-87-1 Ladda ner SDF Lagring av stamlösningar

Synonymer Azidothymidine, NSC 602670 Smiles CC1=CN(C(=O)NC1=O)C2CC(C(O2)CO)N=[N+]=[N-]

Löslighet (Solubility)

In vitro
Batch:

DMSO : 53 mg/mL (198.32 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Ethanol : 53 mg/mL

Water : 26 mg/mL

Molaritetsräknare

Massa Koncentration Volym Molekylvikt
Utspädningsräknare Molekylviktsräknare

In vivo
Batch:

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

mg/kg g μL

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH2O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC50/Ki
Reverse transcriptase
In vitro

Zidovudine pretreatment has potent anti-HIV-1 activity in the newly infected T and monocytic cells but not in chronically infected cells. Inhibition of reverse transcription by this compound decreases p24 antigen levels modestly, decreased HIV-1 gag by 19-fold, and inhibits detection of 2-LTR HIV-1 DNA. This compound and dideoxynucleosides deplete wild-type mitochondrial DNA levels and increase deletedmitochondrial DNA levels in cultured Kearns-Sayre syndrome fibroblasts. This chemical (AZT, 0.1-50 mM) has a concentration dependent suppressive effect on the growth of granulocyte-monocyte colony forming unit (CFU-GM) derived colonies. This compound exposure also induces a concentration dependent suppressive effect (35-90%) on GM-CSF receptor type alpha (GM-CSFR alpha) gene expression. It causes a much lower decrease (15-22%) on the IL-3 receptor type alpha (IL-3R alpha) message level, and has an insignificant effect on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and c-myc message levels. This chemical causes a concentration-dependent inhibition in the levels of the mRNA of Epo receptors and c-fos, whereas the level of c-myc mRNA is unaffected. It also inhibits protein kinase C (PKC) activity in a concentration- and time-dependent manner, causing 50% inhibition at 10 mM within 3 hours. This compound-induced down-regulation of Epo receptors and c-fos expression coupled with inhibition of Epo receptor-mediated signal transduction through PKC are significant contributory factors to AZT-induced erythroid toxicity. This compound could decrease the HDR efficiency. It decrease CRISPR-mediated sequence-specific genome knockin events while increases knockout efficiency .
Referenser
  • [4] https://pubmed.ncbi.nlm.nih.gov/12084393/
  • [5] https://pubmed.ncbi.nlm.nih.gov/7646543/
  • [6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461869/

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer Rekrytering Tillstånd Sponsor/Samarbetspartners Startdatum Faser
NCT03991013 Completed
HIV Infections
University of Cape Town|Wellcome Trust|Médecins Sans Frontières Belgium
 August 8 2019 Phase 2
NCT03642704 Completed
Mother to Child HIV Transmission
ANRS Emerging Infectious Diseases
 February 22 2017 Phase 4

Vanliga frågor (Frequently Asked Questions)

Fråga 1:
Do you happen to have any information regarding its half-life?

Svar:
Its half-life in human is available (http://www.rxlist.com/retrovir-drug/clinical-pharmacology.htm), about 0.5-3 hours in adult subjects.