Peringatan Keamanan

There is limited information regarding the acute toxicity (LD₅₀) and overdose of denileukin diftitox.

Denileukin diftitox

DB00004

biotech approved investigational

Deskripsi

Denileukin diftitox is an IL2-receptor-directed cytotoxin, is a recombinant DNA-derived fusion protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met₁-Thr₃₈₇)-His and the sequence for human interleukin-2 (IL-2; Ala₁-Thr₁₃₃).^L51254 It is designed to deliver diphtheria toxin into IL-2 receptor-expressing cancer cells to cause cell death.A264349, L51254

Denileukin diftitox was originally approved by the FDA in 1999 for the treatment of cutaneous T-cell lymphoma (CTCL),A264339, L51264 making it the first fusion protein cytotoxin approved to treat a human disease in the US.^A264344 In 2014, it was withdrawn voluntarily from the market due to manufacturing issues; however, the biologics license application (BLA) for denileukin diftitox was resubmitted, and it was approved on August 8, 2024.^L51264

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 arithmetic mean (CV%) denileukin diftitox terminal half-life is 112 minutes (31%) on the first day of the first cycle.[L51254]

Volume Distribusi The geometric mean (CV%) volume of distribution of denileukin diftitox is 5.0 L (43%) on the first day of the first administration cycle.[L51254]

Klirens (Clearance) The geometric mean (CV%) clearance is 36.5 mL/min (73%) after the first dose of denileukin diftitox at the recommended dose level.[L51254]

Absorpsi

Following a single dose of denileukin diftitox 9 mcg/kg via one-hour infusion in patients with CTCL, the geometric mean (coefficient of variation CV%) maximum serum concentration (C_max) was 94.4 ng/mL (77%) and area under the concentration over time curve (AUC_0-inf) was 20700 ng x min/L (60%) on the first day of the first administration cycle. There is no accumulation after repeated daily dosing.^L51254

Metabolisme

Denileukin diftitox is expected to be metabolized into small peptides by catabolic pathways.^L51254

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

38 Data

Darbepoetin alfa	The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Denileukin diftitox.
Erythropoietin	The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Denileukin diftitox.
Peginesatide	The risk or severity of Thrombosis can be increased when Peginesatide is combined with Denileukin diftitox.
Methoxy polyethylene glycol-epoetin beta	The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Denileukin diftitox.
Lidocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Lidocaine.
Ropivacaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Ropivacaine.
Bupivacaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Bupivacaine.
Cinchocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Cinchocaine.
Dyclonine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Dyclonine.
Procaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Procaine.
Prilocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Prilocaine.
Proparacaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Proparacaine.
Meloxicam	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Meloxicam.
Oxybuprocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Oxybuprocaine.
Cocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Cocaine.
Mepivacaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Mepivacaine.
Levobupivacaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Levobupivacaine.
Diphenhydramine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Diphenhydramine.
Benzocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Benzocaine.
Chloroprocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Chloroprocaine.
Phenol	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Phenol.
Tetrodotoxin	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Tetrodotoxin.
Benzyl alcohol	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Benzyl alcohol.
Capsaicin	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Capsaicin.
Etidocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Etidocaine.
Articaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Articaine.
Tetracaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Tetracaine.
Propoxycaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Propoxycaine.
Pramocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Pramocaine.
Butamben	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Butamben.
Butacaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Butacaine.
Oxetacaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Oxetacaine.
Ethyl chloride	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Ethyl chloride.
Butanilicaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Butanilicaine.
Metabutethamine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Metabutethamine.
Quinisocaine	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Quinisocaine.
Ambroxol	The risk or severity of methemoglobinemia can be increased when Denileukin diftitox is combined with Ambroxol.
Etrasimod	The risk or severity of immunosuppression can be increased when Denileukin diftitox is combined with Etrasimod.

Target Protein

Interleukin-2 receptor subunit alpha IL2RA

Interleukin-2 receptor subunit beta IL2RB

Referensi & Sumber

Artikel (PubMed)

PMID: 17187516
Turturro F: Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid-derived disorders. Expert Rev Anticancer Ther. 2007 Jan;7(1):11-7.
PMID: 19817678
Manoukian G, Hagemeister F: Denileukin diftitox: a novel immunotoxin. Expert Opin Biol Ther. 2009 Nov;9(11):1445-51. doi: 10.1517/14712590903348135.
PMID: 21188096
Lansigan F, Stearns DM, Foss F: Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma. Cancer Manag Res. 2010 Feb 5;2:53-9. doi: 10.2147/cmar.s5009.
PMID: 22738414
Prince HM, Martin AG, Olsen EA, Fivenson DP, Duvic M: Denileukin diftitox for the treatment of CD25 low-expression mycosis fungoides and Sezary syndrome. Leuk Lymphoma. 2013 Jan;54(1):69-75. doi: 10.3109/10428194.2012.706286. Epub 2012 Sep 14.

Link

Contoh Produk & Brand

Produk: 1 • International brands: 0

Produk

Ontak

Injection, solution • 150 ug/1mL • Intravenous • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.