Zidovudine-d₄  (Synonyms: Azidothymidine-d₄; AZT-d₄; ZDV-d₄)

Zidovudine-d₄ is deuterated labeled Zidovudine (HY-17413). Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI), widely used to treat HIV infection. Zidovudine increases CRISPR/Cas9-mediated editing frequency.

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Zidovudine inhibits SVG, Primary human fetal astrocytes (PFA), peripheral blood mononuclear cells (PBMC), and monocyte-derived macrophages (MDM) with EC₅₀ of 17, 1311, 8, and 5 nM, respectively. Zidovudine inhibits SVG, PFA, PBMC, and MDM with EC₉₀ of 0.205 μM, 44.157 μM, 0.481 μM, and 0.219 μM, respectively^[2]. Genome editing via CRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of living cells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has been considered as an important therapeutic target for AIDS. CXCR4 mediates viral entry into human CD4⁺ cells by binding to envelope protein, gp120. Human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to HIV-1 resistance of human primary CD4⁺ T cells. The Cas9-mediated ablation of CXCR4 demonstrated high specificity and negligible off-target effects without affecting cell division and propagation^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Intravitrous injection of the NRTIs Lamivudine (3TC), Zidovudine (AZT), or Abacavir (ABC) suppresses the laser-induced choroidal neovascularization (CNV) in wild-type mice compared to PBS vehicle. The mean level of VEGF-A in the RPE/choroid, which peaks on day 3 after laser injury, is significantly reduced in 3TC-, AZT- and ABC-treated eyes compared with control eyes in wild-type mice, but not inP2rx7^-/- mice^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

271.27

C₁₀H₉D₄N₅O₄

30516-87-1

OC[C@@H]1[C@@H](N=[N+]=[N-])C[C@H](N2C(NC(C(C([2H])([2H])[2H])=C2[2H])=O)=O)O1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Gray LR, et al. The NRTIs lamivudine, stavudine and zidovudine have reduced HIV-1 inhibitory activity in astrocytes. PLoS One. 2013 Apr 16;8(4):e62196.  [Content Brief]

  [3]. Mizutani T, et al. Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice. Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7122-9.  [Content Brief]

  [4]. Hou P, et al. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci Rep. 2015 Oct 20;5:15577.  [Content Brief]