Peringatan Keamanan

Single injection to adult monkeys produced apparent acute neurological impairment.

Nusinersen

DB13161

small molecule approved investigational

Deskripsi

An antisense oligonucleotide that induces survival motor neuron (SMN) protein expression, it was approved by the U.S. FDA in December, 2016 as Spinraza for the treatment of children and adults with spinal muscular atrophy (SMA). It is adminstrated as direct intrathecal injection.

Struktur Molekul 2D

Struktur tidak tersedia

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) The mean terminal elimination half-life is estimated to be 135 to 177 days in CSF, and 63 to 87 days in plasma [FDA Label].

Volume Distribusi CSF: 0.4 L Plasma: 29 L

Klirens (Clearance) Slow clearance is observed

Absorpsi

Intrathecal injection of nusinersen into the cerebrospinal fluid (CSF) allows it to be distributed from the CSF to the target central nervous system (CNS) tissues. Following intrathecal administration, trough plasma concentrations of nusinersen were relatively low, compared to the trough CSF concentration. Median plasma Tmax values ranged from 1.7 to 6.0 hours. Mean plasma Cmax and AUC values increased approximately dose-proportionally up to a dose of 12 mg.

Metabolisme

Nusinersen is metabolized via exonuclease (3’- and 5’)-mediated hydrolysis primarily at the 3' end of the oligonucleotide. It is not a substrate for, or inhibitor or inducer of CYP450 enzymes. N-1 metabolites of the drug can be detected in the cerebrospinal fluid while N-1,2,3 metabolites can be predominantly detected in the plasma ^L322.

Rute Eliminasi

Excreted by the kidney as chain-shortened oligonucleotides, which are not considered pharmacologically active.

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Survival motor neuron protein SMN2

Referensi & Sumber

Artikel (PubMed)

PMID: 26823478
Hache M, Swoboda KJ, Sethna N, Farrow-Gillespie A, Khandji A, Xia S, Bishop KM: Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. J Child Neurol. 2016 Jun;31(7):899-906. doi: 10.1177/0883073815627882. Epub 2016 Jan 27.

Link

Contoh Produk & Brand

Produk: 3 • International brands: 0

Produk

Spinraza

Injection, solution • 2.4 mg/1mL • Intrathecal • US • Approved
Spinraza

Solution • 2.4 mg / mL • Intrathecal • Canada • Approved
Spinraza

Injection, solution • 12 mg • Intrathecal • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.