Garetosmab

DB16379

biotech investigational

Deskripsi

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of episodic, progressive heterotropic ossification. FOP is characterized by episodic inflammatory episodes, which may be precipitated by trauma, including immunizations and minor tissue damage, which usually result in ossification of the lesion.^A242297 Patients experience abnormal cartilage formation, growth plate dysplasia, and joint issues, resulting in progressive immobility and associated comorbidities.A242297, A242307 The discovery of an activating mutation in the ACVR1 receptor that renders it responsive to the (normally antagonistic) Activin A led to an interest in Activin A as a therapeutic target.A242302, A242307

Garetosmab is under investigation in clinical trial NCT04577820 (Study to Assess the Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva (FOP)).

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) -

Volume Distribusi Garetosmab had a steady-state volume of distribution between 41.4 ± 4.66 and 47.8 ± 4.70 ml/kg following a single IV dose of 0.3-10 mg/kg in healthy women.[A242317]

Klirens (Clearance) When administered as a single IV dose of 0.3-10 mg/kg in healthy women, Garetosmab clearance decreases with increasing dose from 4.35 ± 1.11 mL/day/kg at 0.3 mg/kg down to 1.34 ± 0.149 mL/day/kg at 10 mg/kg.[A242317]

Absorpsi

Garetosmab, administered as a single intravenous dose to healthy females had a mean C_max of between 8.10 ± 0.929 and 378 ± 39.7 mg/L for doses ranging between 0.3-10 mg/kg. The C_max was achieved in a median of 0.06-0.10 days, regardless of dose. Over the same dose range, the AUC_0-? ranged from 72.2 ± 15.4 to 7520 ± 809 mg\*day/L.^A242317 When administered as a single subcutaneous dose of 300 mg, garetosmab had a C_max of 31.6 ± 7.94 mg/L, a T_max of 20.9 (range 6.88-21.0) days, and an AUC_0-? of 1334 ± 376 mg\*day/L.^A242317

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Inhibin beta A chain INHBA

Referensi & Sumber

Artikel (PubMed)

PMID: 32730934
Kaplan FS, Al Mukaddam M, Stanley A, Towler OW, Shore EM: Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis. Bone. 2020 Nov;140:115539. doi: 10.1016/j.bone.2020.115539. Epub 2020 Jul 27.
PMID: 16642017
Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006 May;38(5):525-7. Epub 2006 Apr 23.
PMID: 32515349
Aykul S, Corpina RA, Goebel EJ, Cunanan CJ, Dimitriou A, Kim HJ, Zhang Q, Rafique A, Leidich R, Wang X, McClain J, Jimenez J, Nannuru KC, Rothman NJ, Lees-Shepard JB, Martinez-Hackert E, Murphy AJ, Thompson TB, Economides AN, Idone V: Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop. Elife. 2020 Jun 9;9. pii: 54582. doi: 10.7554/eLife.54582.
PMID: 26333933
Hatsell SJ, Idone V, Wolken DM, Huang L, Kim HJ, Wang L, Wen X, Nannuru KC, Jimenez J, Xie L, Das N, Makhoul G, Chernomorsky R, D'Ambrosio D, Corpina RA, Schoenherr CJ, Feeley K, Yu PB, Yancopoulos GD, Murphy AJ, Economides AN: ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci Transl Med. 2015 Sep 2;7(303):303ra137. doi: 10.1126/scitranslmed.aac4358.
PMID: 30501012
Wentworth KL, Masharani U, Hsiao EC: Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva. Br J Clin Pharmacol. 2019 Jun;85(6):1180-1187. doi: 10.1111/bcp.13823. Epub 2019 Jan 6.
PMID: 33459118
Kaplon H, Reichert JM: Antibodies to watch in 2021. MAbs. 2021 Jan-Dec;13(1):1860476. doi: 10.1080/19420862.2020.1860476.
PMID: 32557665
Vanhoutte F, Liang S, Ruddy M, Zhao A, Drewery T, Wang Y, DelGizzi R, Forleo-Neto E, Rajadhyaksha M, Herman G, Davis JD: Pharmacokinetics and Pharmacodynamics of Garetosmab (Anti-Activin A): Results From a First-in-Human Phase 1 Study. J Clin Pharmacol. 2020 Nov;60(11):1424-1431. doi: 10.1002/jcph.1638. Epub 2020 Jun 18.

Contoh Produk & Brand

Produk: 0 • International brands: 0

Belum ada data produk/brand untuk obat ini pada database. Jalankan import DrugBank untuk mengisi field produk/brand.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.