Branaplam (hydrochloride)

Branaplam (LMI070; NVS-SM1) hydrochloride is a highly potent, selective and orally active survival motor neuron-2 (SMN2) splicing modulator with an EC₅₀ of 20 nM for SMN. Branaplam hydrochloride inhibits human-ether-a-go-go-related gene (hERG) with an IC₅₀ of 6.3 μM. Branaplam hydrochloride elevates full-length SMN protein and extends survival in a severe spinal muscular atrophy (SMA) mouse model^[1][2]. In Vitro: Branaplam (LMI070; NVS-SM1) hydrochloride treatment induces changes in the levels of 175 genes in human fibroblasts^[1].
In Vivo: Branaplam (LMI070; NVS-SM1; 3, 10, 30 mg/kg; oral) hydrochloride produces dose-dependent elevations of SMN2-FL transcript and SMN protein in brain and spinal cord^[1].
Branaplam (1 mg/kg of IV; 3 mg/kg of PO) hydrochloride has a CL of 25 mL/min/kg and an AUC of 3.03 μM?h^[2].
A single Branaplam (oral; 30 mg/kg) hydrochloride results in significant and durable SMN protein elevation in brain for up to 160 hours in C/+ mice^[1].
Branaplam (oral; 0.03, 0.1, 0.3, 1, 3 mg/kg) hydrochloride improves body weight and extendes lifespan in n SMNΔ7 mice^[1].