Peringatan Keamanan

Trifarotene does not appear to carry any risk of carcinogenesis when used at standard doses.^L9013 Systemic exposures in mice following both topical and oral administration were up to 1642 times higher than those seen in humans at the maximal recommended human dose, and these systemic concentrations did not result in observed carcinogenicity. Data regarding overdosage of trifarotene is unavailable.

Trifarotene

DB12808

small molecule approved investigational

Deskripsi

Trifarotene is a topical retinoid cream used in the treatment of acne vulgaris that was first approved for use in the United States in October 2019.^L9013 Retinoids are a class of medications structurally and functionally analogous to vitamin A, though later generation retinoids such as trifarotene and adapalene bear little structural resemblance to vitamin A and are analogous only in function.^A187081 Trifarotene is considered the first of the "fourth-generation" retinoids due to its uniquely selective activity - this selectivity appears to confer improved efficacy and reduced side effects as compared to older, less selective retinoids.^A187054

Struktur Molekul 2D

Berat 459.586

Wujud solid

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 terminal half-life of trifarotene is typically between 2 to 9 hours.[L9013]

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

Systemic absorption of trifarotene is minimal. In a pharmacokinetic study involving 19 subjects, systemic concentrations were only quantifiable in 7 - steady state C_max values ranged from undetectable (<5 pg/mL) to 10 pg/mL and AUC_0-24h ranged from 75 to 104 pg.h/mL.^L9013

Metabolisme

Trifarotene is rapidly metabolized in human hepatocytes - its observed half-life in human keratinocytes is >24 hours, whereas half-life in human liver microsomes is approximately 5 minutes.^A187054 Metabolism of trifarotene is catalyzed primarily by CYP2C9, CYP3A4, CYP2C8, and, to a lesser extent, CYP2B6.^L9013

Rute Eliminasi

Trifarotene is eliminated primarily in the feces.^L9013

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Retinoic acid receptor gamma RARG

Retinoic acid receptor beta RARB

Retinoic acid receptor alpha RARA

Referensi & Sumber

Synthesis reference: Thoreau, E. et. al. Structure-based design of Trifarotene (CD5789), a potent and selective RAR? agonist for the treatment of acne. Bioorganic & Medicinal Chemistry Letters, Volume 28, Issue 10. 2018.

Artikel (PubMed)

PMID: 29974453
Aubert J, Piwnica D, Bertino B, Blanchet-Rethore S, Carlavan I, Deret S, Dreno B, Gamboa B, Jomard A, Luzy AP, Mauvais P, Mounier C, Pascau J, Pelisson I, Portal T, Rivier M, Rossio P, Thoreau E, Vial E, Voegel JJ: Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-gamma agonist trifarotene. Br J Dermatol. 2018 Aug;179(2):442-456. doi: 10.1111/bjd.16719. Epub 2018 Jul 4.
PMID: 30141539
Balak DMW: Topical trifarotene: a new retinoid. Br J Dermatol. 2018 Aug;179(2):231-232. doi: 10.1111/bjd.16733.
PMID: 31306527
Blume-Peytavi U, Fowler J, Kemeny L, Draelos Z, Cook-Bolden F, Dirschka T, Eichenfield L, Graeber M, Ahmad F, Alio Saenz A, Rich P, Tanghetti E: Long-term safety and efficacy of trifarotene 50 mug/g cream, a first-in-class RAR-gamma selective topical retinoid, in patients with moderate facial and truncal acne. J Eur Acad Dermatol Venereol. 2019 Jul 15. doi: 10.1111/jdv.15794.
PMID: 30802558
Tan J, Thiboutot D, Popp G, Gooderham M, Lynde C, Del Rosso J, Weiss J, Blume-Peytavi U, Weglovska J, Johnson S, Parish L, Witkowska D, Sanchez Colon N, Alio Saenz A, Ahmad F, Graeber M, Stein Gold L: Randomized phase 3 evaluation of trifarotene 50 mug/g cream treatment of moderate facial and truncal acne. J Am Acad Dermatol. 2019 Jun;80(6):1691-1699. doi: 10.1016/j.jaad.2019.02.044. Epub 2019 Feb 22.
PMID: 30586483
Chien A: Retinoids in Acne Management: Review of Current Understanding, Future Considerations, and Focus on Topical Treatments J Drugs Dermatol. 2018 Dec 1;17(12):s51-55.

Link

FDA Approved Drugs: Aklief®

Contoh Produk & Brand

Produk: 2 • International brands: 0

Produk

Aklief

Cream • 50 mcg / g • Topical • Canada • Approved
Aklief

Cream • 50 ug/1g • Topical • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.