smn protein

Risdiplam (RG7916) is a centrally and peripherally distributed and orally administrable small molecule SMN2 pre-mRNA splicing modifier that increases survival motor neuron (SMN) protein levels.

RG7800 hydrochloride is an orally active modulator of SMN2 splicing.

MF-DH-300 is a 15-PGDH inhibitor that prevents the binding of 15-PGDH and PGE2, thereby promoting stem cell proliferation, enhancing muscle strength, and improving mitochondrial function. MF-DH-300 increases the expression of survival motor neuron (SMN) protein and is suitable for research on muscle diseases such as spinal muscular atrophy (SMA).

D-156844 (Compound 11a) hydrochloride is an SMN2 promoter activator with an EC50 of 4 nM. It enhances mRNA expression of the mouse SMN in NSC-34 cells and the human SMN2 promoter in fibroblasts from patients with severe type I spinal muscular atrophy (SMA), along with increasing full-length human SMN protein expression. D-156844 hydrochloride can overcome DHFR inhibition and is used in SMA research.

Branaplam is a highly potent, selective and orally active SMN2 splicing modulator. Branaplam increases the amount of functional SMN protein produced by the SMN2 gene through modifying its splicing.

Rg3039 (PF-06687859) is a potent DcpS inhibitor. DcpS is a therapeutic target for spinal muscular atrophy. Spinal muscular atrophy (SMA) is caused by deletion or mutation of both copies of the SMN1 gene which produces an essential protein known as SMN. RG3039 improves motor function in SMA mice. RG3039 also showed activity to improve survival, function and motor unit pathologies in two SMA mouse models.

NVS-SM2 is an effective small molecule splicing enhancer of SMN2 with oral activity. NVS-SM2 showed increased exon 7 inclusion and upregulated SMN protein expression in SMA fibroblasts and SMN cells Δ7 5025 mouse myoblasts.

SMN2-Stablizer-27 is a stablizer of survival of motor neuron 2 (SMN2), and a post-translationally stablizing SMN protein for the treatment of spinal muscular atrophy (SMA).

The Survival of Motor Neurons (SMN) protein participates in RNA splicing. Decreases in SMN, typically a consequence of defects in the smn1 gene, result in the death of motor neurons and lead to the neurodegenerative disease, spinal muscular atrophy (SMA). Cuspin-1 is a small molecule upregulator of SMN that has been shown in vitro to increase levels of SMN in SMA patient fibroblasts by 50% at 18 μM. Its mechanism of action is thought to involve increased phosphorylation of ERK to initiate Ras-Raf-MEK signaling, which results in an increased rate of SMN translation.

Branaplam hydrochloride (LMI070; NVS-SM1) is a selective and orally active SMN2 splicing modulator that acts directly on SMN with an EC50 value of 20 nM. Branaplam hydrochloride also inhibits hERG channels, demonstrating an IC50 of 6.3 μM. In a mouse model of severe spinal muscular atrophy (SMA), Branaplam hydrochloride significantly increased full-length SMN protein levels and markedly improved survival.

RG7800 hydrochloride is an orally active SMN2 splicing modulator with EC50 values of 23 nM for splicing and 87 nM for SMN protein production, holding promise as a therapeutic agent for [spinal muscular atrophy].

Risdiplam-D4 is the deuterated form of Risdiplam. Risdiplam (T16757) (RG7916) is a splicing modifier of precursor mRNA for the survival motor neuron gene SMN2, which enhances the levels of SMN protein.