In mice, subcutaneous administration of nedosiran at doses up to 2000 mg/kg/dose (approximately 58 times the maximum recommended human dose (MRHD) based on body surface area (BSA)) or a mouse-specific (pharmacologically active) analog (10 mg/kg/dose) during organogenesis (dosing on gestation days 6, 8, 10, 12, and 14 for nedosiran; gestation days 3 and 10 for the analog) did not have adverse effects on embryofetal development.L48320
Subcutaneous administration of nedosiran (0, 2, 6, or 20 mg/kg/dose) to pregnant rabbits during organogenesis (dosing on gestation days 7, 9, 11, 13, 15, 17, and 19) resulted in maternal toxicity on the basis of body weight loss of up to 6.5% following the first dose in the 6 and 20 mg/kg/dose groups. Higher post-implantation loss and lower numbers of live fetuses occurred at ? 6 mg/kg/dose (exposures equivalent to the MRHD based on BSA), and fetal cardiovascular and skeletal malformations occurred at the 20 mg/kg/dose (2 times the MRHD based on BSA). No adverse findings were seen at the 2 mg/kg/dose, which is below the MRHD.L48320
In a pre-and postnatal study in mice, subcutaneous administration of nedosiran (0, 250, 500, or 1000 mg/kg/dose) or a mouse-specific (pharmacologically active) analog (10 mg/kg/dose) from implantation (dosing on gestational days 6, 8, 10, 12, 14, 16) to weaning (dosing on lactation days 1, 8 15, 20) did not have adverse effects on the growth, viability, development and reproductive performance of the offspring.L48320
Long-term studies to assess the carcinogenic risk of nedosiran have not been conducted.L48320
Nedosiran was not genotoxic in the in vitro bacterial mutagenicity, in vitro micronucleus assays (human peripheral blood lymphocytes), and in vivo bone marrow micronucleus assay in mice.L48320
Weekly subcutaneous administration of nedosiran at doses of 500, 1000, or 2000 mg/kg or of a mouse-specific (pharmacologically active) analog at a dose of 10 mg/kg to male mice for 4 weeks prior to and throughout mating, and to female mice for 2 weeks prior to and throughout mating and to gestation day 7 did not affect male or female fertility or early embryonic development.L48320
Nedosiran is an RNA interference targeting hepatic lactate dehydrogenase, the enzyme responsible for the conversion of glyoxylate to oxalate.A261690 Oxalate, particularly calcium oxalate, precipitation is the main cause of kidney stones formation; therefore, blocking the production of oxalate can help alleviate renal symptoms.A261685
Nedosiran was approved by the FDA on October 2nd, 2023, under the brand name RIVFLOZA to lower urinary oxalate levels in children 9 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. This approval is based on the favorable results from the pivotal phase 2 PHYOXTM2 and interim data from the ongoing phase 3 PHYOXTM3 clinical trials.L48325
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).
drugbank-id dan name pada skema XML DrugBank.targets/target yang memuat polipeptida sasaran.gene-name dan varian snp-effects.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.