Peringatan Keamanan

Repeat-dose toxicity studies in juvenile rats showed an increase in the development of hematologic malignancies at doses of 10 mg/kg, a dose approximately 8-fold higher than the maximum recommended human dose (MRHD).^L42455 Fertility studies in rats observed effects on female (but not male) fertility at doses approximately 7-fold higher than the MRHD.^L42455

Luspatercept

DB12281

biotech approved investigational

Deskripsi

Luspatercept is a recombinant fusion protein comprised of a modified extracellular domain of activin receptor type IIB fused to the FC domain of human IgG1.A187829,L42455 It was first approved for use in the United States in November 2019 under the brand name Reblozyl® for the treatment of anemia in patients with beta thalassemia who require regular blood transfusions.^L42455 Luspatercept is novel in that it ameliorates anemia via action on late-stage erythropoiesis, in contrast to typical erythropoiesis-stimulating agents (ESAs), such as darbepoetin alfa and epoetin alfa, which act only on early-stage erythropoiesis.^A187835 Luspatercept's novel mechanism of action, then, is uniquely suited for the treatment of conditions in which late-stage erythropoiesis is defective, such as beta thalassemia and other myelodysplastic diseases.A187835,A187838

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 average half-life of luspatercept is approximately 11 days.[L42455]

Volume Distribusi The average apparent volume of distribution is 7.1 L.[L42455]

Klirens (Clearance) The total apparent clearance of luspatercept is 0.44 L/day.[L42455]

Absorpsi

At doses of 1 mg/kg and 1.25 mg/kg, the average steady-state AUC was 126 day•?g/mL and 157 day•?g/mL and the average C_max was 8.17 ?g/mL and 10.2 ?g/mL, respectively.^L42455 Steady-state was reached after 3 doses given every 3 weeks. T_max is reached approximately 7 days after administration.^L42455 Absorption pharmacokinetics do not appear to be affected by the site of subcutaneous injection.

Metabolisme

As luspatercept is a fusion protein, it is expected to undergo catabolism into amino acids by general protein degradation processes.^L42455

Rute Eliminasi

Data eliminasi belum tersedia.

Interaksi Obat

0 Data

Tidak ada data.

Referensi & Sumber

Artikel (PubMed)

PMID: 28958287
Mies A, Platzbecker U: Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-beta superfamily inhibitors. Semin Hematol. 2017 Jul;54(3):141-146. doi: 10.1053/j.seminhematol.2017.06.004. Epub 2017 Jul 4.
PMID: 30617198
Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM: Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.
PMID: 31395583
Camaschella C: GDF11 is not the target of luspatercept. Blood. 2019 Aug 8;134(6):500-501. doi: 10.1182/blood.2019001983.
PMID: 24658078
Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, Davies MV, Alexander MJ, Devine M, Loveday KS, Underwood KW, Grinberg AV, Quisel JD, Chopra R, Pearsall RS, Seehra J, Kumar R: Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014 Apr;20(4):408-14. doi: 10.1038/nm.3512. Epub 2014 Mar 23.
PMID: 31394818
Kubasch AS, Platzbecker U: Setting Fire to ESA and EMA Resistance: New Targeted Treatment Options in Lower Risk Myelodysplastic Syndromes. Int J Mol Sci. 2019 Aug 7;20(16). pii: ijms20163853. doi: 10.3390/ijms20163853.

Link

Contoh Produk & Brand

Produk: 6 • International brands: 0

Produk

Reblozyl

Injection, powder, lyophilized, for solution • 25 mg/1 • Subcutaneous • US • Approved
Reblozyl

Injection, powder, lyophilized, for solution • 75 mg/1 • Subcutaneous • US • Approved
Reblozyl

Injection, powder, for solution • 25 mg • Subcutaneous • EU • Approved
Reblozyl

Injection, powder, for solution • 75 mg • Subcutaneous • EU • Approved
Reblozyl

Powder, for solution • 25 mg / vial • Subcutaneous • Canada • Approved
Reblozyl

Powder, for solution • 75 mg / vial • Subcutaneous • Canada • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.