Risdiplam

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Cat Number

API1825352655

CAS Number

1825352-65-5

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Product Detail Description Scientific Support Customer Q&A

CAS Number

1825352-65-5

EINECS

841-610-4

Storage

Dry, dark and at 0 - 4℃ for short term (days to weeks) or -20℃ for long term (months to years).

Synonyms

RG-7916; RO7034067; 7-(4,7-diazaspiro[2.5]oct-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one

Molecular Formula

C22H23N7O

Molecular Weight

401.5

Smiles

O=C1C=C(C2=NN3C(C(C)=C2)=NC(C)=C3)N=C4N1C=C(N(C5)CCNC65CC6)C=C4

Appearance

Solid

General Description

Risdiplam is a small-molecule heterocyclic with a unique chemical structure that of an innovative, orally bioavailable, small-molecule, nitrogen-containing heterocyclic derivative. It has an optimal molecular lipophilicity and low molecular weight that allows it to cross the blood-brain barrier and provides widespread distribution systemically to the central nervous system and peripheral tissues.

Mechanism of Action

Risdiplam is an SMN2 pre-mRNA splicing modifier that is brain-penetrant, developed to treat SMA caused by SMN1 biallelic mutations resulting in a deficiency of SMN protein. Risdiplam corrected SMN2 splicing by promoting the inclusion of exon 7 into the mRNA transcript (achieved by binding to the 5' splice site of intron 7 and to exonic splicing enhancer 2 in exon 7 in SMN2 pre-mRNA), thereby increasing the production of full-length (and therefore functional) SMN protein in the brain. Risdiplam has been shown to increase SMN protein levels in SMA patient-derived fibroblasts as well as in motor neurons in vitro.

Application

Risdiplam's main use is for the treatment of spinal muscular atrophy (SMA). It is the first orally-administered approved therapy for SMA. Since the drug is able to cross the blood-brain barrier and distribute uniformly across the central nervous system and peripheral tissues, risdiplam can be used to systemically treat patients with all types of SMA (type 1, 2 and 3).

Risdiplam is an orally available small molecule splicing modifier, which systemically targets the underlying genetic defect in SMA. It acts through a dual mode of action to promote exon 7 inclusion of SMN2. Risdiplam functions by binding to and stabilizing the transient RNA duplex between the weak 5’ splice site in SMN2 exon 7 and U1 snRNP complex, thereby increasing the binding affinity of U1 snRNP to 5’ splice site in a sequence-selective manner. Risdiplam also directly binds to the ESE2 motif in SMN2 exon 7. These two mechanisms, which lead to a 'gain of function', rescue the SMN2 'incomplete' or 'inefficient' splicing to produce functional SMN protein, to overcome the absence of SMN1. The ability of risdiplam to both target the 5' splice site-U1 snRNP interaction, as well as ESE2, provides high specificity to SMN2 splicing correction, with preserved systemic bioavailability.

Fig. 1 Mode of action of risdiplam. (Ratni H, et al. 2021)

References

Ratni H, et al. Risdiplam, the first approved small molecule splicing modifier drug as a blueprint for future transformative medicines. ACS medicinal chemistry letters. 2021, 12(6): 874-877.

Does Risdiplam require light-protected storage conditions?

Yes, Risdiplam is photosensitive and must be kept in light-resistant containers to avoid chemical degradation.

Can I track my Risdiplam shipment in real-time?

We provide automated tracking updates via email as soon as your Risdiplam leaves our distribution center.

What documents are included in a standard Risdiplam shipment?

Each Risdiplam delivery includes a comprehensive COA, MSDS, and a detailed list.

Do you offer bulk discounts for long-term Risdiplam contracts?

We provide competitive pricing structures for customers looking for long-term, high-volume Risdiplam supply agreements.