Peringatan Keamanan

Hypersensitivity reactions such as contact urticaria may occur and discontinuation of the treatment is advised. No evidence of mutagenic or clastrogenic potential as well as altered effects on fertility. Oral LD50 value for rats is >500mg/kg.

Crisaborole

DB05219

small molecule approved investigational

Deskripsi

Crisaborole is a novel oxaborole approved by FDA on December 14, 2016 as Eucrisa, a topical treatment of for mild to moderate atopic dermatitis.
This non-steroidal agent is efficacious in improving disease severity, reducing the risk of infection and reducing the signs and symptoms in patients 2 years old and older. It reduces the local inflammation in the skin and prevents further exacerbation of the disease with a good safety profile. Its structure contains a boron atom, which facilitates skin penetration and binding to the bimetal center of the phosphodiesterase 4 enzyme. It is currently under development as topical treatment of psoriasis.

Struktur Molekul 2D

Berat 251.05

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) -

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

Systemic concentrations of crisaborole were reached by 8 days of twice-daily topical administration. It has low systemic absorption thus poses less risk for developing systemic side effects.

Metabolisme

Crisaborole is substantially metabolized into inactive metabolites. The major metabolite 5-(4-cyanophenoxy)-2-hydroxyl benzylalcohol (metabolite 1), is formed via hydrolysis; this metabolite is further metabolized into downstream metabolites, among which 5-(4-cyanophenoxy)-2-hydroxyl benzoic acid (metabolite 2), formed via oxidation, is also a major metabolite.

Rute Eliminasi

Renal excretion of metabolites is the major route of elimination.

Interaksi Obat

6 Data

Daprodustat	The metabolism of Daprodustat can be decreased when combined with Crisaborole.
Erdafitinib	The serum concentration of Erdafitinib can be increased when it is combined with Crisaborole.
Etrasimod	The serum concentration of Etrasimod can be increased when it is combined with Crisaborole.
Resmetirom	The metabolism of Resmetirom can be decreased when combined with Crisaborole.
Tovorafenib	The metabolism of Tovorafenib can be decreased when combined with Crisaborole.
Deuruxolitinib	The metabolism of Deuruxolitinib can be decreased when combined with Crisaborole.

Target Protein

3',5'-cyclic-AMP phosphodiesterase 4A PDE4A

3',5'-cyclic-AMP phosphodiesterase 4B PDE4B

3',5'-cyclic-AMP phosphodiesterase 4C PDE4C

3',5'-cyclic-AMP phosphodiesterase 4D PDE4D

Referensi & Sumber

Artikel (PubMed)

PMID: 27417017
Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, Eichenfield LF, Forsha DW, Rees WC, Simpson EL, Spellman MC, Stein Gold LF, Zaenglein AL, Hughes MH, Zane LT, Hebert AA: Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016 Sep;75(3):494-503.e4. doi: 10.1016/j.jaad.2016.05.046. Epub 2016 Jul 11.
PMID: 28492291
Paton DM: Crisaborole: Phosphodiesterase inhibitor for treatment of atopic dermatitis. Drugs Today (Barc). 2017 Apr;53(4):239-245. doi: 10.1358/dot.2017.53.4.2604174.
PMID: 27335049
Zane LT, Hughes MH, Shakib S: Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers. Am J Clin Dermatol. 2016 Oct;17(5):519-526.
PMID: 24852768
Moustafa F, Feldman SR: A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology. Dermatol Online J. 2014 May 16;20(5):22608.

Contoh Produk & Brand

Produk: 7 • International brands: 0

Produk

Eucrisa

Ointment • 20 mg/1g • Topical • US • Approved
Eucrisa

Ointment • 2 % w/w • Topical • Canada • Approved
Staquis

Ointment • 20 mg/g • Cutaneous • EU
Staquis

Ointment • 20 mg/g • Cutaneous • EU
Staquis

Ointment • 20 mg/g • Cutaneous • EU
Staquis

Ointment • 20 mg/g • Cutaneous • EU
Staquis

Ointment • 20 mg/1g • Topical • US

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.