Peringatan Keamanan

There is no experience regarding human overdose with deuruxolitinib. There is no specific antidote for overdose with deuruxolitinib. Treatment should be symptomatic and supportive and monitor patients for signs and symptoms of adverse reactions.^L51068 There is no information regarding the acute toxicity (LD₅₀) of deuruxolitinib.

Deuruxolitinib

DB18847

small molecule investigational

Deskripsi

Deuruxolitinib is a deuterated form of ruxolitinib that selectively inhibits Janus kinases (JAK) JAK1 and JAK2. Deuteration allows the drug to circumvent extensive oxidative metabolism around the cyclopentyl ring, which increases the duration of the pharmacological activity of deuruxolitinib.^A264113

On July 26, 2024, deuruxolitinib was approved by the FDA for the treatment of severe alopecia areata.^L51083 Alopecia areata is an autoimmune condition that attacks the hair follicles and leads to unpredictable hair loss in the scalp and other areas of the body.^A264108 The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway has been implicated in the pathophysiology of alopecia areata, as it regulates the expression of inflammatory mediators.A264108, A264113, A264123 Deuruxolitinib works to block the inflammatory responses caused by JAKs.^L51068

Struktur Molekul 2D

Berat 314.422

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 mean elimination half-life is approximately four hours.[L51068]

Volume Distribusi The steady-state volume of distribution is approximately 50 L.[L51068]

Klirens (Clearance) -

Absorpsi

Following oral administration of deuruxolitinib, Cmax and AUCs increased dose-proportionally over a dose range from 8 mg to 48 mg (6 times the approved recommended dosage) in healthy subjects. Steady-state plasma concentrations were achieved within one to two days, with minimal accumulation, after twice daily administration.^L51068 Deuruxolitinib bioavailability is 90%, with peak plasma concentrations reached within 1.5 hours.^L51068 No clinically significant differences in the pharmacokinetics of deuruxolitinib were observed following the administration of a high-fat, high-calorie meal (approximately 50% fat and 800-1000 calories).^L51068

Metabolisme

Deuruxolitinib is primarily metabolized by CYP2C9 (76%) and CYP3A4 (21%) and to a lesser extent by CYP1A2 (3%). The two most abundant human metabolites C-21714 and C-21717, each of which accounted for approximately 5% of total drug-related AUC and both are approximately 10-fold less pharmacologically active than deuruxolitinib.^L51068 The exact metabolic pathways of deuruxolitinib and the structures of its metabolites have not been fully characterized.

Rute Eliminasi

After a single dose of radiolabeled deuruxolitinib, there was no unchanged dose recovered in either urine or feces.^L51068

Interaksi Makanan

1 Data

1. Take with or without food. Food had negligible effects on deuruxolitinib phramacokinetics.

Interaksi Obat

393 Data

Phenytoin	The metabolism of Deuruxolitinib can be increased when combined with Phenytoin.
Pentobarbital	The metabolism of Deuruxolitinib can be increased when combined with Pentobarbital.
Carbamazepine	The metabolism of Deuruxolitinib can be increased when combined with Carbamazepine.
Mitotane	The metabolism of Deuruxolitinib can be increased when combined with Mitotane.
Primidone	The metabolism of Deuruxolitinib can be increased when combined with Primidone.
Rifampin	The metabolism of Deuruxolitinib can be increased when combined with Rifampin.
Phenobarbital	The metabolism of Deuruxolitinib can be increased when combined with Phenobarbital.
Rifapentine	The metabolism of Deuruxolitinib can be increased when combined with Rifapentine.
Dexamethasone	The metabolism of Deuruxolitinib can be increased when combined with Dexamethasone.
Fosphenytoin	The metabolism of Deuruxolitinib can be increased when combined with Fosphenytoin.
St. John's Wort	The metabolism of Deuruxolitinib can be increased when combined with St. John's Wort.
Midostaurin	The metabolism of Deuruxolitinib can be increased when combined with Midostaurin.
Enzalutamide	The metabolism of Deuruxolitinib can be increased when combined with Enzalutamide.
Lumacaftor	The metabolism of Deuruxolitinib can be increased when combined with Lumacaftor.
Apalutamide	The metabolism of Deuruxolitinib can be increased when combined with Apalutamide.
Cyclosporine	The metabolism of Deuruxolitinib can be decreased when combined with Cyclosporine.
Fluvoxamine	The metabolism of Deuruxolitinib can be decreased when combined with Fluvoxamine.
Fluconazole	The metabolism of Deuruxolitinib can be decreased when combined with Fluconazole.
Erythromycin	The serum concentration of Deuruxolitinib can be increased when it is combined with Erythromycin.
Ziprasidone	The metabolism of Deuruxolitinib can be decreased when combined with Ziprasidone.
Isradipine	The metabolism of Deuruxolitinib can be decreased when combined with Isradipine.
Diltiazem	The metabolism of Deuruxolitinib can be decreased when combined with Diltiazem.
Clozapine	The metabolism of Deuruxolitinib can be decreased when combined with Clozapine.
Haloperidol	The serum concentration of Haloperidol can be increased when it is combined with Deuruxolitinib.
Ciprofloxacin	The metabolism of Deuruxolitinib can be decreased when combined with Ciprofloxacin.
Voriconazole	The metabolism of Deuruxolitinib can be decreased when combined with Voriconazole.
Nicardipine	The metabolism of Deuruxolitinib can be decreased when combined with Nicardipine.
Verapamil	The metabolism of Deuruxolitinib can be decreased when combined with Verapamil.
Aprepitant	The metabolism of Deuruxolitinib can be decreased when combined with Aprepitant.
Isoniazid	The metabolism of Deuruxolitinib can be decreased when combined with Isoniazid.
Primaquine	The metabolism of Deuruxolitinib can be decreased when combined with Primaquine.
Miconazole	The metabolism of Deuruxolitinib can be decreased when combined with Miconazole.
Danazol	The metabolism of Deuruxolitinib can be decreased when combined with Danazol.
Fusidic acid	The metabolism of Deuruxolitinib can be decreased when combined with Fusidic acid.
Zimelidine	The metabolism of Deuruxolitinib can be decreased when combined with Zimelidine.
Dronedarone	The metabolism of Deuruxolitinib can be decreased when combined with Dronedarone.
Milnacipran	The metabolism of Deuruxolitinib can be decreased when combined with Milnacipran.
Simeprevir	The metabolism of Deuruxolitinib can be decreased when combined with Simeprevir.
Isavuconazonium	The metabolism of Deuruxolitinib can be decreased when combined with Isavuconazonium.
Desvenlafaxine	The metabolism of Deuruxolitinib can be decreased when combined with Desvenlafaxine.
Nilvadipine	The metabolism of Deuruxolitinib can be decreased when combined with Nilvadipine.
Seproxetine	The metabolism of Deuruxolitinib can be decreased when combined with Seproxetine.
Linagliptin	The metabolism of Deuruxolitinib can be decreased when combined with Linagliptin.
Indalpine	The metabolism of Deuruxolitinib can be decreased when combined with Indalpine.
Netupitant	The metabolism of Deuruxolitinib can be decreased when combined with Netupitant.
Barnidipine	The metabolism of Deuruxolitinib can be decreased when combined with Barnidipine.
Benidipine	The metabolism of Deuruxolitinib can be decreased when combined with Benidipine.
Venetoclax	The metabolism of Deuruxolitinib can be decreased when combined with Venetoclax.
Isavuconazole	The metabolism of Deuruxolitinib can be decreased when combined with Isavuconazole.
Fosnetupitant	The metabolism of Deuruxolitinib can be decreased when combined with Fosnetupitant.
Berotralstat	The metabolism of Deuruxolitinib can be decreased when combined with Berotralstat.
Nelfinavir	The metabolism of Deuruxolitinib can be decreased when combined with Nelfinavir.
Indinavir	The metabolism of Deuruxolitinib can be decreased when combined with Indinavir.
Terfenadine	The metabolism of Deuruxolitinib can be decreased when combined with Terfenadine.
Ritonavir	The serum concentration of Deuruxolitinib can be increased when it is combined with Ritonavir.
Efavirenz	The metabolism of Deuruxolitinib can be decreased when combined with Efavirenz.
Ergotamine	The metabolism of Deuruxolitinib can be decreased when combined with Ergotamine.
Amprenavir	The metabolism of Deuruxolitinib can be decreased when combined with Amprenavir.
Delavirdine	The metabolism of Deuruxolitinib can be decreased when combined with Delavirdine.
Methimazole	The metabolism of Deuruxolitinib can be decreased when combined with Methimazole.
Conivaptan	The metabolism of Deuruxolitinib can be decreased when combined with Conivaptan.
Tipranavir	The metabolism of Deuruxolitinib can be decreased when combined with Tipranavir.
Telithromycin	The metabolism of Deuruxolitinib can be decreased when combined with Telithromycin.
Ketoconazole	The metabolism of Deuruxolitinib can be decreased when combined with Ketoconazole.
Atazanavir	The metabolism of Deuruxolitinib can be decreased when combined with Atazanavir.
Amiodarone	The metabolism of Deuruxolitinib can be decreased when combined with Amiodarone.
Nefazodone	The metabolism of Deuruxolitinib can be decreased when combined with Nefazodone.
Itraconazole	The metabolism of Deuruxolitinib can be decreased when combined with Itraconazole.
Clarithromycin	The metabolism of Deuruxolitinib can be decreased when combined with Clarithromycin.
Saquinavir	The metabolism of Deuruxolitinib can be decreased when combined with Saquinavir.
Posaconazole	The metabolism of Deuruxolitinib can be decreased when combined with Posaconazole.
Darunavir	The metabolism of Deuruxolitinib can be decreased when combined with Darunavir.
Lopinavir	The metabolism of Deuruxolitinib can be decreased when combined with Lopinavir.
Ditiocarb	The metabolism of Deuruxolitinib can be decreased when combined with Ditiocarb.
Nilotinib	The metabolism of Deuruxolitinib can be decreased when combined with Nilotinib.
Telaprevir	The metabolism of Deuruxolitinib can be decreased when combined with Telaprevir.
Levoketoconazole	The metabolism of Deuruxolitinib can be decreased when combined with Levoketoconazole.
Lonafarnib	The metabolism of Deuruxolitinib can be decreased when combined with Lonafarnib.
Boceprevir	The metabolism of Deuruxolitinib can be decreased when combined with Boceprevir.
Elvitegravir	The metabolism of Deuruxolitinib can be decreased when combined with Elvitegravir.
Stiripentol	The metabolism of Deuruxolitinib can be decreased when combined with Stiripentol.
Curcumin	The metabolism of Deuruxolitinib can be decreased when combined with Curcumin.
Ribociclib	The metabolism of Deuruxolitinib can be decreased when combined with Ribociclib.
Danoprevir	The metabolism of Deuruxolitinib can be decreased when combined with Danoprevir.
Troleandomycin	The metabolism of Deuruxolitinib can be decreased when combined with Troleandomycin.
Troglitazone	The metabolism of Deuruxolitinib can be decreased when combined with Troglitazone.
Valproic acid	The metabolism of Deuruxolitinib can be decreased when combined with Valproic acid.
Imatinib	The metabolism of Deuruxolitinib can be decreased when combined with Imatinib.
Mifepristone	The metabolism of Deuruxolitinib can be decreased when combined with Mifepristone.
Quinidine	The metabolism of Deuruxolitinib can be decreased when combined with Quinidine.
Felbamate	The metabolism of Deuruxolitinib can be decreased when combined with Felbamate.
Sulfinpyrazone	The metabolism of Deuruxolitinib can be decreased when combined with Sulfinpyrazone.
Iproniazid	The metabolism of Deuruxolitinib can be decreased when combined with Iproniazid.
Medical Cannabis	The metabolism of Deuruxolitinib can be decreased when combined with Medical Cannabis.
Dabrafenib	The metabolism of Deuruxolitinib can be increased when combined with Dabrafenib.
Floxuridine	The metabolism of Deuruxolitinib can be decreased when combined with Floxuridine.
Capecitabine	The metabolism of Deuruxolitinib can be decreased when combined with Capecitabine.
Gemfibrozil	The metabolism of Deuruxolitinib can be decreased when combined with Gemfibrozil.
Sulfaphenazole	The metabolism of Deuruxolitinib can be decreased when combined with Sulfaphenazole.
Tepotinib	The metabolism of Deuruxolitinib can be decreased when combined with Tepotinib.

Target Protein

Tyrosine-protein kinase JAK2 JAK2

Tyrosine-protein kinase JAK1 JAK1

Non-receptor tyrosine-protein kinase TYK2 TYK2

Referensi & Sumber

Artikel (PubMed)

PMID: 35364216
King B, Mesinkovska N, Mirmirani P, Bruce S, Kempers S, Guttman-Yassky E, Roberts JL, McMichael A, Colavincenzo M, Hamilton C, Braman V, Cassella JV: Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata. J Am Acad Dermatol. 2022 Aug;87(2):306-313. doi: 10.1016/j.jaad.2022.03.045. Epub 2022 Mar 29.
PMID: 38659584
Yan T, Wang T, Tang M, Liu N: Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis. Front Pharmacol. 2024 Apr 10;15:1372810. doi: 10.3389/fphar.2024.1372810. eCollection 2024.
PMID: 36695751
Barati Sedeh F, Michaelsdottir TE, Henning MAS, Jemec GBE, Ibler KS: Comparative Efficacy and Safety of Janus Kinase Inhibitors Used in Alopecia Areata: A Systematic Review and Meta-analysis. Acta Derm Venereol. 2023 Jan 25;103:adv00855. doi: 10.2340/actadv.v103.4536.
PMID: 37521227
Sardana K, Bathula S, Khurana A: Which is the Ideal JAK Inhibitor for Alopecia Areata - Baricitinib, Tofacitinib, Ritlecitinib or Ifidancitinib - Revisiting the Immunomechanisms of the JAK Pathway. Indian Dermatol Online J. 2023 Jun 28;14(4):465-474. doi: 10.4103/idoj.idoj45222. eCollection 2023 Jul-Aug.

Link

Contoh Produk & Brand

Produk: 0 • International brands: 0

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.