Eteplirsen

Eteplirsen (AVI 4658) is a phosphorylated diamine morpholino oligonucleotide that targets exon 51 of the human Duchenne muscular dystrophy (DMD) gene. Eteplirsen induces exon 51 skipping, causing it to be skipped during splicing, thereby restoring the translation reading frame and producing a shortened functional dystrophin. Eteplirsen can be used in research on Duchenne muscular dystrophy^[1][2][3][4]. In Vitro:Eteplirsen (AVI 4658) (100 nM; 24 h) induces exon 51 skipping in the tri-chromatic reporter cell line (Flp-In CHO cells harboring the DMD exon 51 minigene)^[4].
Eteplirsen (10 µM; 24 h) induces exon 51 skipping in differentiated human rhabdomyosarcoma (RD) cells^[4].
Eteplirsen (100 nM; 24 h) promotes exon 51 skipping in the tri-chromatic reporter cell line, leads to the expression of TagRFP-conjugated proteins as a readout of successful splicing modulation^[4]. In Vivo:Eteplirsen (AVI 4658) (up to 320 mg/kg; i.v. or s.c.; once weekly for 12 weeks) is well tolerated in cynomolgus monkeys. No drug related adverse impacts are observed^[2].
Eteplirsen (up to 320 mg/kg; i.v. or s.c.; once weekly for 12 weeks) induces dose-dependent microscopic renal effects in cynomolgus monkeys, including basophilic granules (minimal), basophilic tubules (minimal to moderate), and tubular vacuolation (minimal to mild), Eteplirsen (AVI 4658) sodium-induced renal effects are reversible after a 28-day recovery period ^[2].
Eteplirsen (up to 320 mg/kg; i.v.; single dose or up to 320 mg/kg; s.c.; once weekly for 4 weeks) exhibits no test article-related effects on cardiovascular, respiratory, global neurological, renal, or liver parameters in cynomolgus monkeys at the maximum feasible dose^[3].
Eteplirsen (up to 2000 mg/kg; i.v.; single dose) shows no mutagenic potential in the mouse bone marrow erythrocyte micronucleus test^[3].