Peringatan Keamanan

Toxicity information regarding enfortumab vedotin is not readily available. Patients experiencing an overdose are likely at an increased risk of severe adverse effects such as significant nausea, vomiting, neuropathy, or rash.^L10836 Symptomatic and supportive measures are recommended.

Enfortumab vedotin

DB13007

biotech approved investigational

Deskripsi

Enfortumab vedotin is an antibody-drug conjugate used in the treatment of patients with advanced, treatment-resistant urothelial cancers.^L10836 It is comprised of a fully human monoclonal antibody targeted against Nectin-4 and a microtubule-disrupting chemotherapeutic agent, monomethyl auristatin E (MMAE), joined by a protease-cleavable link.^L10836 It is similar to brentuximab vedotin, another antibody conjugated with MMAE that targets CD-30 instead of Nectin-4.

The clinical development of enfortumab vedotin was the result of a collaboration between Astellas Pharma and Seattle Genetics ^A188868 and it was first approved for use in the United States in December 2019 under the brand name Padcev^TM.^L10836 Enfortumab vedotin was later approved by the European Commission on April 13, 2022.^L42000

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 elimination half-lives of enfortumab vedotin and MMAE are 3.4 days and 2.4 days, respectively.[L10836]

Volume Distribusi The estimated steady-state volume of distribution is 11 L.[L10836]

Klirens (Clearance) The mean clearance of enfortumab vedotin and free MMAE was 0.10 L/h and 2.7 L/h, respectively.[L10836] The clearance of MMAE appears to be limited by its rate of release from enfortumab vedotin.

Absorpsi

Following the first treatment cycle, C_max and AUC_0-28d for enfortumab vedotin were 28 µg/mL and 111 µg.d/mL, respectively. The C_max and AUC_0-28d of unconjugated MMAE following the same cycle were 4.8 ng/mL and 69 ng.d/mL, respectively.^L10836 The T_max of MMAE is 1-3 days following the end of the infusion.^A188865

Metabolisme

The catabolism of enfortumab vedotin has not been studied in humans.^L10836 Given its structure, it is expected to be catabolized to smaller peptides, amino acids, unconjugated MMAE, and MMAE metabolites. MMAE is released from enfortumab vedotin via proteolytic cleavage by intracellular proteases and is metabolized primarily by CYP3A4 in vitro.^L10836

Rute Eliminasi

Excretion kinetics have not been fully characterized, but may be extrapolated from data available from another MMAE-containing antibody-drug conjugate - kinetic studies of this drug demonstrated that 17% of the total MMAE administered was recovered in feces, and 6% was recovered in urine, primarily as unchanged drug, over a 1-week period.^L10836

Interaksi Obat

342 Data

Ranolazine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Ranolazine.
Lumacaftor	The serum concentration of Enfortumab vedotin can be decreased when it is combined with Lumacaftor.
Vemurafenib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Vemurafenib.
Apalutamide	The serum concentration of Enfortumab vedotin can be decreased when it is combined with Apalutamide.
Pitolisant	The serum concentration of Enfortumab vedotin can be decreased when it is combined with Pitolisant.
Isavuconazole	The serum concentration of Enfortumab vedotin can be increased when it is combined with Isavuconazole.
Isavuconazonium	The serum concentration of Enfortumab vedotin can be increased when it is combined with Isavuconazonium.
Fluconazole	The metabolism of Enfortumab vedotin can be decreased when combined with Fluconazole.
Erythromycin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Erythromycin.
Sildenafil	The serum concentration of Enfortumab vedotin can be increased when it is combined with Sildenafil.
Reserpine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Reserpine.
Sorafenib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Sorafenib.
Loxapine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Loxapine.
Quinine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Quinine.
Toremifene	The serum concentration of Enfortumab vedotin can be increased when it is combined with Toremifene.
Simvastatin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Simvastatin.
Verapamil	The metabolism of Enfortumab vedotin can be decreased when combined with Verapamil.
Tamoxifen	The serum concentration of Enfortumab vedotin can be increased when it is combined with Tamoxifen.
Mifepristone	The serum concentration of Enfortumab vedotin can be increased when it is combined with Mifepristone.
Vardenafil	The serum concentration of Enfortumab vedotin can be increased when it is combined with Vardenafil.
Tacrolimus	The serum concentration of Enfortumab vedotin can be increased when it is combined with Tacrolimus.
Quinidine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Quinidine.
Zonisamide	The serum concentration of Enfortumab vedotin can be increased when it is combined with Zonisamide.
Carvedilol	The serum concentration of Enfortumab vedotin can be increased when it is combined with Carvedilol.
Propafenone	The serum concentration of Enfortumab vedotin can be increased when it is combined with Propafenone.
Lapatinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Lapatinib.
Paliperidone	The serum concentration of Enfortumab vedotin can be increased when it is combined with Paliperidone.
Mibefradil	The serum concentration of Enfortumab vedotin can be increased when it is combined with Mibefradil.
Biricodar	The serum concentration of Enfortumab vedotin can be increased when it is combined with Biricodar.
Dronedarone	The metabolism of Enfortumab vedotin can be decreased when combined with Dronedarone.
Elacridar	The serum concentration of Enfortumab vedotin can be increased when it is combined with Elacridar.
Flibanserin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Flibanserin.
Vandetanib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Vandetanib.
Zosuquidar	The serum concentration of Enfortumab vedotin can be increased when it is combined with Zosuquidar.
Tariquidar	The serum concentration of Enfortumab vedotin can be increased when it is combined with Tariquidar.
Temsirolimus	The serum concentration of Enfortumab vedotin can be increased when it is combined with Temsirolimus.
Simeprevir	The metabolism of Enfortumab vedotin can be decreased when combined with Simeprevir.
Brefeldin A	The serum concentration of Enfortumab vedotin can be increased when it is combined with Brefeldin A.
Ticagrelor	The serum concentration of Enfortumab vedotin can be increased when it is combined with Ticagrelor.
Ivacaftor	The serum concentration of Enfortumab vedotin can be increased when it is combined with Ivacaftor.
Lomitapide	The serum concentration of Enfortumab vedotin can be increased when it is combined with Lomitapide.
Crizotinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Crizotinib.
Linagliptin	The metabolism of Enfortumab vedotin can be decreased when combined with Linagliptin.
Mirabegron	The serum concentration of Enfortumab vedotin can be increased when it is combined with Mirabegron.
Regorafenib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Regorafenib.
Ponatinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Ponatinib.
Canagliflozin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Canagliflozin.
Afatinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Afatinib.
Ledipasvir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Ledipasvir.
Vorapaxar	The serum concentration of Enfortumab vedotin can be increased when it is combined with Vorapaxar.
Suvorexant	The serum concentration of Enfortumab vedotin can be increased when it is combined with Suvorexant.
Netupitant	The metabolism of Enfortumab vedotin can be decreased when combined with Netupitant.
Palbociclib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Palbociclib.
Daclatasvir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Daclatasvir.
Niguldipine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Niguldipine.
Rolapitant	The serum concentration of Enfortumab vedotin can be increased when it is combined with Rolapitant.
Venetoclax	The metabolism of Enfortumab vedotin can be decreased when combined with Venetoclax.
Asunaprevir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Asunaprevir.
Velpatasvir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Velpatasvir.
Istradefylline	The serum concentration of Enfortumab vedotin can be increased when it is combined with Istradefylline.
Neratinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Neratinib.
Valspodar	The serum concentration of Enfortumab vedotin can be increased when it is combined with Valspodar.
Dacomitinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Dacomitinib.
Glasdegib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Glasdegib.
Entrectinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Entrectinib.
Voxilaprevir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Voxilaprevir.
Sarecycline	The serum concentration of Enfortumab vedotin can be increased when it is combined with Sarecycline.
Fedratinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Fedratinib.
Laniquidar	The serum concentration of Enfortumab vedotin can be increased when it is combined with Laniquidar.
Enasidenib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Enasidenib.
Pibrentasvir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Pibrentasvir.
Glecaprevir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Glecaprevir.
Dexniguldipine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Dexniguldipine.
ONT-093	The serum concentration of Enfortumab vedotin can be increased when it is combined with ONT-093.
Ivosidenib	The metabolism of Enfortumab vedotin can be increased when combined with Ivosidenib.
Norgestimate	The serum concentration of Enfortumab vedotin can be increased when it is combined with Norgestimate.
Carfilzomib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Carfilzomib.
Favipiravir	The serum concentration of Enfortumab vedotin can be increased when it is combined with Favipiravir.
Methylene blue	The serum concentration of Enfortumab vedotin can be increased when it is combined with Methylene blue.
Ripretinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Ripretinib.
Pralsetinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Pralsetinib.
Clofazimine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Clofazimine.
Arsenic trioxide	The serum concentration of Enfortumab vedotin can be increased when it is combined with Arsenic trioxide.
Mefloquine	The serum concentration of Enfortumab vedotin can be increased when it is combined with Mefloquine.
Cethromycin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Cethromycin.
Ixabepilone	The serum concentration of Enfortumab vedotin can be increased when it is combined with Ixabepilone.
Voclosporin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Voclosporin.
Eliglustat	The serum concentration of Enfortumab vedotin can be increased when it is combined with Eliglustat.
Umbralisib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Umbralisib.
Diosmin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Diosmin.
Sapropterin	The serum concentration of Enfortumab vedotin can be increased when it is combined with Sapropterin.
Levoketoconazole	The serum concentration of Enfortumab vedotin can be increased when it is combined with Levoketoconazole.
Capmatinib	The serum concentration of Enfortumab vedotin can be increased when it is combined with Capmatinib.
Belumosudil	The serum concentration of Enfortumab vedotin can be increased when it is combined with Belumosudil.
Metreleptin	The metabolism of Enfortumab vedotin can be increased when combined with Metreleptin.
Digitoxin	The serum concentration of Digitoxin can be increased when it is combined with Enfortumab vedotin.
Cyclosporine	The metabolism of Enfortumab vedotin can be decreased when combined with Cyclosporine.
Digoxin	The serum concentration of Digoxin can be increased when it is combined with Enfortumab vedotin.
Vincristine	The serum concentration of Vincristine can be increased when it is combined with Enfortumab vedotin.
Sirolimus	The serum concentration of Sirolimus can be increased when it is combined with Enfortumab vedotin.

Target Protein

Nectin-4 NECTIN4

Referensi & Sumber

Artikel (PubMed)

PMID: 31823332
Hanna KS: Clinical Overview of Enfortumab Vedotin in the Management of Locally Advanced or Metastatic Urothelial Carcinoma. Drugs. 2019 Dec 10. pii: 10.1007/s40265-019-01241-7. doi: 10.1007/s40265-019-01241-7.
PMID: 31526130
McGregor BA, Sonpavde G: Enfortumab Vedotin, a fully human monoclonal antibody against Nectin 4 conjugated to monomethyl auristatin E for metastatic urothelial Carcinoma. Expert Opin Investig Drugs. 2019 Oct;28(10):821-826. doi: 10.1080/13543784.2019.1667332. Epub 2019 Sep 17.

Link

Contoh Produk & Brand

Produk: 6 • International brands: 0

Produk

Padcev

Injection, powder, for solution • 20 mg • Intravenous • EU • Approved
Padcev

Injection, powder, for solution • 30 mg • Intravenous • EU • Approved
Padcev

Powder, for solution • 20 mg / vial • Intravenous • Canada • Approved
Padcev

Powder, for solution • 30 mg / vial • Intravenous • Canada • Approved
Padcev Ejfv

Injection, powder, lyophilized, for solution • 20 mg/2mL • Intravenous • US • Approved
Padcev Ejfv

Injection, powder, lyophilized, for solution • 30 mg/3mL • Intravenous • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.