Peringatan Keamanan

Data regarding overdose of N4-hydroxycytidine is not readily available. The therapeutic index of N4-hydroxycytidine against a clinical isolate of SARS-CoV-2 is expected to be >100, with an in vitro IC₅₀ of 0.3µM and a CC₅₀ of >10µM.^A193014

N4-Hydroxycytidine

DB15660

small molecule experimental

Deskripsi

N4-Hydroxyctidine, or EIDD-1931, is a ribonucleoside analog which induces mutations in RNA virions.A193008,A193011 N4-hydroxycytidine was first described in the literature in 1980 as a potent mutagen of bacteria and phage.^A193023 It has shown antiviral activity against Venezuelan equine encephalitis virus,^A193008 and the human coronavirus HCoV-NL63 in vitro.^A193017 N4-hydroxycytodine has been shown to inhibit SARS-CoV-2 as well as other human and bat coronaviruses in mice and human airway epithelial cells.^A193014 It is orally bioavailable in mice and distributes into tissue before becoming the active 5’-triphosphate form, which is incorporated into the genome of new virions, resulting in the accumulation of inactivating mutations.^A193011 In non-human primates, N4-hydroxycytidine was poorly orally bioavailable.^A193026 A remdesivir resistant mutant mouse hepatitis virus has also been shown to have increased sensitivity to N4-hydroxycytidine.^A193014 The prodrug of N4-hydroxycytidine, EIDD-2801, is also being investigated for its broad spectrum activity against the coronavirus family of viruses.^A193014

Struktur Molekul 2D

Berat 259.218

Wujud -

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) -

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

N4-hydroxycytidine is orally bioavailable in mice^A193011 but poorly bioavailable in non-human primates.^A193026

Metabolisme

N4-hydroxycytidine distributes into tissues where it is is phosphorylated to the 5'-triphosphate form.^A193026

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

0 Data

Tidak ada data.

Referensi & Sumber

Artikel (PubMed)

PMID: 29167335
Urakova N, Kuznetsova V, Crossman DK, Sokratian A, Guthrie DB, Kolykhalov AA, Lockwood MA, Natchus MG, Crowley MR, Painter GR, Frolova EI, Frolov I: beta-d-N (4)-Hydroxycytidine Is a Potent Anti-alphavirus Compound That Induces a High Level of Mutations in the Viral Genome. J Virol. 2018 Jan 17;92(3). pii: JVI.01965-17. doi: 10.1128/JVI.01965-17. Print 2018 Feb 1.
PMID: 31494195
Painter GR, Bowen RA, Bluemling GR, DeBergh J, Edpuganti V, Gruddanti PR, Guthrie DB, Hager M, Kuiper DL, Lockwood MA, Mitchell DG, Natchus MG, Sticher ZM, Kolykhalov AA: The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection. Antiviral Res. 2019 Nov;171:104597. doi: 10.1016/j.antiviral.2019.104597. Epub 2019 Sep 5.
PMID: -
T. P. Sheahan et al.: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci. Transl. Med..
PMID: 16723558
Pyrc K, Bosch BJ, Berkhout B, Jebbink MF, Dijkman R, Rottier P, van der Hoek L: Inhibition of human coronavirus NL63 infection at early stages of the replication cycle. Antimicrob Agents Chemother. 2006 Jun;50(6):2000-8. doi: 10.1128/AAC.01598-05.
PMID: 7366595
Sledziewska E, Janion C: Mutagenic specificity of N4-hydroxycytidine. Mutat Res. 1980 Mar;70(1):11-6. doi: 10.1016/0027-5107(80)90053-6.
PMID: 31645453
Toots M, Yoon JJ, Cox RM, Hart M, Sticher ZM, Makhsous N, Plesker R, Barrena AH, Reddy PG, Mitchell DG, Shean RC, Bluemling GR, Kolykhalov AA, Greninger AL, Natchus MG, Painter GR, Plemper RK: Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci Transl Med. 2019 Oct 23;11(515). pii: 11/515/eaax5866. doi: 10.1126/scitranslmed.aax5866.
PMID: 31910262
Hampton T: New Flu Antiviral Candidate May Thwart Drug Resistance. JAMA. 2020 Jan 7;323(1):17. doi: 10.1001/jama.2019.20225.

Contoh Produk & Brand

Produk: 0 • International brands: 0

Belum ada data produk/brand untuk obat ini pada database. Jalankan import DrugBank untuk mengisi field produk/brand.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.