Risdiplam | CAS#1825352-65-5 | gene splicing modulator

MedKoo Cat#: 561863 | Name: Risdiplam

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Risdiplam, also known as RG7916 and RO7034067, is a gene splicing modulator (neuromuscular disease). Risdiplam has been seen to alleviate symptoms associated with spinal muscular atrophy.

Chemical Structure

Risdiplam

CAS#1825352-65-5

Theoretical Analysis

MedKoo Cat#: 561863

Name: Risdiplam

CAS#: 1825352-65-5

Chemical Formula: C22H23N7O

Exact Mass: 401.1964

Molecular Weight: 401.47

Elemental Analysis: C, 65.82; H, 5.77; N, 24.42; O, 3.99

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,350.00	Ready to ship
200mg	USD 2,150.00	Ready to ship
500mg	USD 3,850.00	Ready to ship

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Related CAS #

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Synonym

Risdiplam; RG7916; RG-7916; RG 7916; RO703406; RO-7034067; RO 7034067;

IUPAC/Chemical Name

7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one

InChi Key

ASKZRYGFUPSJPN-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H23N7O/c1-14-9-18(26-29-11-15(2)24-21(14)29)17-10-20(30)28-12-16(3-4-19(28)25-17)27-8-7-23-22(13-27)5-6-22/h3-4,9-12,23H,5-8,13H2,1-2H3

SMILES Code

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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

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

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# T9D06P24

QC Data

View QC data: current batch, Lot# T9D06P24

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Risdiplam (RG7916) is a SMN2 pre-mRNA splicing modifier that increases survival motor neuron (SMN) protein levels.

In vitro activity:

Risdiplam showed an average passive permeability in parental LLC‐PK1 cells of around 350 nm/s. Similar permeability was observed in L‐MDR1, L‐Mdra1, M‐BCRP, and M‐Bcrp cells in the presence of inhibitor. Risdiplam was found not to be a substrate of human MDR1 with an ER of 2.2, but a weak substrate of rodent Mdr1a (ER = 3.7). The predicted CSF‐to‐unbound plasma partition coefficient (pKp,uu) based on the rodent ER and model from is therefore 0.33. Risdiplam was a weak human BCRP substrate with an ER of 3.7 and a strong Bcrp substrate in rodents with an ER of 44. Reference: Pharmacol Res Perspect. 2018 Dec; 6(6): e00447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262736/

In vivo activity:

These findings were confirmed while dosing risdiplam: a similar dose‐dependent increase in SMN protein levels in brain and muscle (0.1 mg/kg/day: brain 28%, muscle 32%; 1 mg/kg/day, brain 206%, muscle 210%) was observed after 7 days of once daily dosing in SMNΔ7 mice (Study 4, n = 6 or 7 per dose) (Figure 7). Risdiplam also prolonged survival of SMNΔ7 mice (Study 5) when dosed once daily with risdiplam for 219 days. In Study 5, SMN protein level increases were measured relative to SMN levels in heterozygous control animals and a correlation was observed between increase in SMN protein in blood and in brain. In the same study, risdiplam was shown to improve phenotype and motor function, to prolong survival and to increase body weight gain in SMNΔ7 mice. Reference: Pharmacol Res Perspect. 2018 Dec; 6(6): e00447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262736/

	Solvent	mg/mL	mM
Solubility
	DMSO	2.0	4.98
	Ethanol	2.0	4.98
	Water	1.0	2.49

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 401.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Poirier A, Weetall M, Heinig K, Bucheli F, Schoenlein K, Alsenz J, Bassett S, Ullah M, Senn C, Ratni H, Naryshkin N, Paushkin S, Mueller L. Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs. Pharmacol Res Perspect. 2018 Nov 29;6(6):e00447. doi: 10.1002/prp2.447. PMID: 30519476; PMCID: PMC6262736.

In vitro protocol:

In vivo protocol:

1: Prior TW, Leach ME, Finanger EL. Spinal Muscular Atrophy. 2000 Feb 24 [updated 2024 Sep 19]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301526. 2: Grandi F, Astord S, Pezet S, Gidaja E, Mazzucchi S, Chapart M, Vasseur S, Mamchaoui K, Smeriglio P. Characterization of SMA Type II Skeletal Muscle from Treated Patients shows Mitochondrial Deficiency and Denervation. JCI Insight. 2024 Sep 12:e180992. doi: 10.1172/jci.insight.180992. Epub ahead of print. PMID: 39264856. 3: Waldrop MA. Clinical decision making around commercial use of gene and genetic therapies for spinal muscular atrophy. Neurotherapeutics. 2024 Sep 5;21(4):e00437. doi: 10.1016/j.neurot.2024.e00437. Epub ahead of print. PMID: 39241317. 4: Haque US, Yokota T. Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges. Genes (Basel). 2024 Jul 30;15(8):999. doi: 10.3390/genes15080999. PMID: 39202360; PMCID: PMC11353366. 5: Cavaloiu B, Simina IE, Vilciu C, Trăilă IA, Puiu M. Nusinersen Improves Motor Function in Type 2 and 3 Spinal Muscular Atrophy Patients across Time. Biomedicines. 2024 Aug 6;12(8):1782. doi: 10.3390/biomedicines12081782. PMID: 39200246; PMCID: PMC11351209. 6: Moon MH, Vock IW, Streit AD, Connor LJ, Senkina J, Ellman JA, Simon MD. Disulfide Tethering to Map Small Molecule Binding Sites Transcriptome-wide. ACS Chem Biol. 2024 Aug 28. doi: 10.1021/acschembio.4c00538. Epub ahead of print. PMID: 39192734. 7: Guo WH, Sun N, Cao L. [Effect of disease-modifying drugs for spinal muscular atrophy on the ventilation support of type 1 children]. Zhonghua Er Ke Za Zhi. 2024 Sep 2;62(9):867-871. Chinese. doi: 10.3760/cma.j.cn112140-20240321-00193. PMID: 39192445. 8: Cooper K, Nalbant G, Sutton A, Harnan S, Thokala P, Chilcott J, McNeill A, Bessey A. Systematic Review of Presymptomatic Treatment for Spinal Muscular Atrophy. Int J Neonatal Screen. 2024 Aug 14;10(3):56. doi: 10.3390/ijns10030056. PMID: 39189228; PMCID: PMC11348213. 9: Yan Y, Feng Y, Jiang L, Jin J, Mao S. Safety of risdiplam in spinal muscular atrophy patients after short-term treatment with nusinersen. Muscle Nerve. 2024 Aug 13. doi: 10.1002/mus.28228. Epub ahead of print. PMID: 39136364. 10: O'Brien K, Nguo K, Yiu EM, Woodcock IR, Billich N, Davidson ZE. Nutrition outcomes of disease modifying therapies in spinal muscular atrophy: A systematic review. Muscle Nerve. 2024 Aug 11. doi: 10.1002/mus.28224. Epub ahead of print. PMID: 39129236. 11: Chen B, Gong Y, Zhou T. The Impact of Nusinersen and Risdiplam on Motor Function for Spinal Muscular Atrophy Type 2 and 3: A Meta-Analysis. J Coll Physicians Surg Pak. 2024 Aug;34(8):948-955. doi: 10.29271/jcpsp.2024.08.948. PMID: 39113515. 12: Xiao L, Amin R. Impact of Disease-modifying Therapies on Respiratory Function in People with Neuromuscular Disorders. Sleep Med Clin. 2024 Sep;19(3):473-483. doi: 10.1016/j.jsmc.2024.04.004. Epub 2024 Jun 4. PMID: 39095144. 13: Ma K, Wang D, Hu W, Wang J, Yu C, Cui Z, Liu F. Emphasis on the importance of comprehensive clinical and genetic analysis - spinal muscular atrophy combined with phenylketonuria: A case report. Medicine (Baltimore). 2024 Aug 2;103(31):e39076. doi: 10.1097/MD.0000000000039076. PMID: 39093767; PMCID: PMC11296489. 14: Wu X, Lin Z, Liu Y, Liu X, Yi Z, Huang X, Zhang J. Analysis of blood concentrations and clinical application of risdiplam in patients with spinal muscular atrophy using ultra-high performance liquid chromatography-tandem mass spectrometry. Biomed Chromatogr. 2024 Jul 15:e5934. doi: 10.1002/bmc.5934. Epub ahead of print. PMID: 39010638. 15: Lim JYX, Wang FS, Ling SR, Tay SKH. A consensus survey of neurologists and clinical geneticists on spinal muscular atrophy treatment in Singapore. Ann Acad Med Singap. 2024 Jun 1;53(6):386-389. doi: 10.47102/annals-acadmedsg.202425. PMID: 38979994. 16: Ruythooren F, Moens P. Spinal Muscular Atrophy Scoliosis in the Era of Background Therapies-A Review of the Literature. J Clin Med. 2024 Jun 14;13(12):3467. doi: 10.3390/jcm13123467. PMID: 38929996; PMCID: PMC11205197. 17: Novikov A, Maldova M, Shamantseva N, Shalmiev I, Shoshina E, Epoyan N, Krutikova N, Moshonkina T. Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs. Biomedicines. 2024 May 24;12(6):1162. doi: 10.3390/biomedicines12061162. PMID: 38927369; PMCID: PMC11200420. 18: Giess D, Erdos J, Wild C. An updated systematic review on spinal muscular atrophy patients treated with nusinersen, onasemnogene abeparvovec (at least 24 months), risdiplam (at least 12 months) or combination therapies. Eur J Paediatr Neurol. 2024 Jul;51:84-92. doi: 10.1016/j.ejpn.2024.06.004. Epub 2024 Jun 17. PMID: 38905882. 19: McPheron MA, Felker MV. Clinical perspectives: Treating spinal muscular atrophy. Mol Ther. 2024 Aug 7;32(8):2489-2504. doi: 10.1016/j.ymthe.2024.06.020. Epub 2024 Jun 18. PMID: 38894541. 20: Novikova ES. Opyt primeneniya risdiplama pri semeinom sluchae spinal'noi myshechnoi atrofii 5q u patsientov s gomozigotnoi deletsiei gena SMN1 i odinakovym kolichestvom kopii gena SMN2 [Experience with the use of risdiplam in a familial case of spinal muscular atrophy 5q in patients with a homozygous deletion of the SMN1 gene and the same copy number of the SMN2 gene]. Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(5):138-141. Russian. doi: 10.17116/jnevro2024124051138. PMID: 38884441.