DRUGphase2splice modifier

branaplam

Mechanism

Small-molecule SMN2 splice modulator. Stabilizes U1 snRNP binding at SMN2 exon 7 5'SS to promote inclusion.

Structure

CC1(CC(CC(N1)(C)C)OC2=NN=C(C=C2)C3=C(C=C(C=C3)C4=CNN=C4)O)C

Related claims (28)

Type	Predicate	Conf	Source
splicing event	Branaplam elevates levels of full-length SMN protein in vivo by modulating the splicing of the related gene SMN2 to enhance the exon-7 inclusion and increase levels of the SMN.	65%	33822618
splicing event	A low-dose treatment of Anti-N1 with either risdiplam or branaplam produces a synergistic effect on the inclusion of SMN2 exon 7 in SMA patient fibroblasts (demonstrated in vitro).	65%	38379891
gene expression	Branaplam treatment increased full-length SMN RNA and protein levels (observed in mouse model).	65%	30407821
gene expression	Combination treatment of Anti-N1 with risdiplam and branaplam results in minimal disruption of gene expression (demonstrated in vitro).	59%	38379891
drug target	Branaplam is a Phase 3 clinical drug targeting SMN1 for the treatment of spinal muscular atrophy.	59%	37594310
splicing event	Both Risdiplam and Branaplam triggered massive perturbations of splicing events, inducing off-target exon inclusion, exon skipping, intron retention, intron removal and alternative splice site usage (observed in SMA patient cells).	59%	37026480
gene expression	Aberrant expression of genes associated with DNA replication, cell cycle, RNA metabolism, cell signaling and metabolic pathways was observed in SMA patient cells treated with Risdiplam and Branaplam.	59%	37026480
splicing event	Branaplam stabilizes the interaction between the spliceosome and SMN2 pre-mRNA.	59%	30407821
splicing event	Risdiplam, branaplam, SMN-CX and SMN-CY switch the splicing of the SMN2 gene (demonstrated in vitro).	59%	38554107
biomarker	NfL may be useful as an exploratory biomarker to assist in detecting and monitoring treatment-related peripheral nerve injury, with or without clinical signs, associated with administration of branaplam and other compounds bearing a neuroto...	59%	37439009
splicing event	The 5'-splice site bulge repair mechanism can be generalised, based on the similar contact of risdiplam, SMN-CX, SMN-CY and branaplam to the RNA epitope (demonstrated in vitro).	59%	38554107
drug efficacy	Branaplam is currently in clinical trials for the treatment of spinal muscular atrophy.	53%	W4377102962
drug efficacy	Branaplam lowers mHTT protein levels in blood samples from Spinal Muscular Atrophy (SMA) Type I patients dosed orally for SMA (clinical trial result)	53%	35241644
gene expression	Branaplam increased the levels of survival motor neuron protein in preclinical studies.	53%	37439009
splicing event	Branaplam is a splicing modulator of survival motor neuron-2 pre-mRNAs.	53%	41579854
splicing event	The results quantitatively characterize the specificities of risdiplam and branaplam for 5' splice site sequences.	53%	38424098
drug efficacy	Branaplam has shown some improvement in treating SMA.	53%	39514016
protein interaction	Risdiplam, SMN-CX, SMN-CY and branaplam contact the RNA epitope similarly to SMN-C5 (demonstrated in vitro).	51%	38554107
drug target	The therapeutic merit of both Risdiplam and Branaplam is based on their ability to restore body-wide inclusion of Survival Motor Neuron 2 (SMN2) exon 7 upon oral administration.	51%	37026480
survival	Branaplam treatment extended survival (observed in mouse model).	47%	30407821
drug target	The effects of orally administered branaplam were evaluated in the SMA neonatal mouse model (SMNΔ7).	45%	34528068
neuroprotection	Orally administered branaplam has no impact on neurogenesis in juvenile animals (observed in mouse model).	45%	34528068
drug target	Branaplam was previously in development to treat spinal muscular atrophy.	45%	38954594
drug target	Risdiplam and branaplam were developed for treating spinal muscular atrophy.	45%	38424098
other	Branaplam was primarily eliminated through metabolism.	43%	41579854
safety	Branaplam was well tolerated in early clinical studies.	39%	37439009
drug efficacy	Branaplam is a splicing modulation therapy for SMA.	39%	EP4084796A1
drug efficacy	Branaplam is in clinical studies for SMA.	39%	30407821

Off-Target Findings (0)

No Boltz-2 / Chai-1 off-target panel claims recorded for this drug.