RG7800 | RG-7800 | RO6885247 | CAS#1449598-06-4 | SMN2 splicing modifier

MedKoo Cat#: 526734 | Name: RG7800

Description:

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

RG7800, also known as RO6885247 is a potent and selective SMN2 splicing modifier, which is currently under human clinical trials for the treatment of Spinal Muscular Atrophy (SMA). SMA is a genetic disorder caused by the mutation or deletion of the survival of motor neuron (SMN1) gene. It affects one in approximately 10,000 live births and in the most severe forms is assocaited with a high rate of childhood mortality. RG7800 exhibits excellent pharmacokinetic and in vivo efficacy and had a favorable safety profile. RG7800 corrects alternative splicing of the human SMN2 gene in the brain of transgenic SMA model mice, leading to an increase of the SMN protein in the brain.

Chemical Structure

RG7800

CAS#1449598-06-4

Theoretical Analysis

MedKoo Cat#: 526734

Name: RG7800

CAS#: 1449598-06-4

Chemical Formula: C24H28N6O

Exact Mass: 416.2325

Molecular Weight: 416.53

Elemental Analysis: C, 69.21; H, 6.78; N, 20.18; O, 3.84

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,750.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 4,950.00	Ready to ship
5g	USD 8,450.00	Ready to ship

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Related CAS #

No Data

Synonym

RG7800; RG-7800; RG 7800; RO6885247; RO-6885247; RO 6885247.

IUPAC/Chemical Name

2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-(1-methylpiperidin-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one

InChi Key

GYFRQCMDLBNZSF-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H28N6O/c1-5-19-22-11-21(27-30(22)13-16(3)25-19)20-12-23(31)29-14-18(10-15(2)24(29)26-20)17-6-8-28(4)9-7-17/h10-14,17H,5-9H2,1-4H3

SMILES Code

O=C1C=C(C2=NN3C(C(CC)=NC(C)=C3)=C2)N=C4N1C=C(C5CCN(C)CC5)C=C4C

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, not in water

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

Spinal muscular atrophy (SMA) is the leading genetic cause of infant and toddler mortality, and there is currently no approved therapy available. SMA is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. These mutations or deletions result in low levels of functional SMN protein. SMN2, a paralogous gene to SMN1, undergoes alternative splicing and exclusion of exon 7, producing an unstable, truncated SMN∆7 protein.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S07S05C09

QC Data

View QC data: current batch, Lot#S07S05C09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

RG7800 is a SMN2 splicing modifier.

In vitro activity:

RG7800 was shown to promote the inclusion of exon 7 in SMN2 mRNA, generating full-length (FL) mRNA in an in vitro assay that assessed the levels of SMN protein in fibroblasts and in spinal motor neurons derived from SMA type I and II patient induced pluripotent stem cells (iPSCs). The maximal increase in SMN protein produced was similar in both cell types, suggesting that RG7800 increases the SMN protein level as a result of correcting the dysfunctional SMN2 splicing. Reference: J Med Chem. 2016 Jul 14;59(13):6086-100. https://pubmed.ncbi.nlm.nih.gov/27299419/

In vivo activity:

Exposure to RG7800 induced changes within the germ cells in the testes of male cynomolgus monkeys and rats. In RG7800-treated monkeys, there was no evidence of damage to spermatogonia. In rats, full reversibility of germ-cell degeneration in the testes was observed among half of the rats following RG7800 cessation. The effects on the male reproductive system are expected to be reversible in humans for these types of SMN2 mRNA-splicing modifiers. Reference: Reprod Toxicol. 2023 Jun;118:108360. https://pubmed.ncbi.nlm.nih.gov/36894038/

	Solvent	mg/mL	mM
Solubility
	DMSO	1.4	3.40
	Ethanol	2.5	6.00
	Water	1.3	3.00

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 416.53 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. Ratni H, Karp GM, Weetall M, Naryshkin NA, Paushkin SV, Chen KS, McCarthy KD, Qi H, Turpoff A, Woll MG, Zhang X, Zhang N, Yang T, Dakka A, Vazirani P, Zhao X, Pinard E, Green L, David-Pierson P, Tuerck D, Poirier A, Muster W, Kirchner S, Mueller L, Gerlach I, Metzger F. Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy. J Med Chem. 2016 Jul 14;59(13):6086-100. doi: 10.1021/acs.jmedchem.6b00459. Epub 2016 Jul 6. PMID: 27299419. 1. Mueller L, Barrow P, Jacobsen B, Ebeling M, Weinbauer G. Reproductive findings in male animals exposed to selective survival of motor neuron 2 (SMN2) gene splicing-modifying agents. Reprod Toxicol. 2023 Jun;118:108360. doi: 10.1016/j.reprotox.2023.108360. Epub 2023 Mar 8. PMID: 36894038. 2. Kletzl H, Marquet A, Günther A, Tang W, Heuberger J, Groeneveld GJ, Birkhoff W, Mercuri E, Lochmüller H, Wood C, Fischer D, Gerlach I, Heinig K, Bugawan T, Dziadek S, Kinch R, Czech C, Khwaja O. The oral splicing modifier RG7800 increases full length survival of motor neuron 2 mRNA and survival of motor neuron protein: Results from trials in healthy adults and patients with spinal muscular atrophy. Neuromuscul Disord. 2019 Jan;29(1):21-29. doi: 10.1016/j.nmd.2018.10.001. Epub 2018 Oct 30. PMID: 30553700.

In vitro protocol:

In vivo protocol:

1. Mueller L, Barrow P, Jacobsen B, Ebeling M, Weinbauer G. Reproductive findings in male animals exposed to selective survival of motor neuron 2 (SMN2) gene splicing-modifying agents. Reprod Toxicol. 2023 Jun;118:108360. doi: 10.1016/j.reprotox.2023.108360. Epub 2023 Mar 8. PMID: 36894038. 2. Kletzl H, Marquet A, Günther A, Tang W, Heuberger J, Groeneveld GJ, Birkhoff W, Mercuri E, Lochmüller H, Wood C, Fischer D, Gerlach I, Heinig K, Bugawan T, Dziadek S, Kinch R, Czech C, Khwaja O. The oral splicing modifier RG7800 increases full length survival of motor neuron 2 mRNA and survival of motor neuron protein: Results from trials in healthy adults and patients with spinal muscular atrophy. Neuromuscul Disord. 2019 Jan;29(1):21-29. doi: 10.1016/j.nmd.2018.10.001. Epub 2018 Oct 30. PMID: 30553700.

1: Chiriboga CA, Bruno C, Duong T, Fischer D, Mercuri E, Kirschner J, Kostera- Pruszczyk A, Jaber B, Gorni K, Kletzl H, Carruthers I, Martin C, Scalco RS, Fontoura P, Muntoni F; JEWELFISH Study Group. JEWELFISH: 24-month results from an open-label study in non-treatment-naïve patients with SMA receiving treatment with risdiplam. J Neurol. 2024 Aug;271(8):4871-4884. doi: 10.1007/s00415-024-12318-z. Epub 2024 May 11. PMID: 38733387; PMCID: PMC11319388. 2: Mueller L, Barrow P, Jacobsen B, Ebeling M, Weinbauer G. Reproductive findings in male animals exposed to selective survival of motor neuron 2 (SMN2) gene splicing-modifying agents. Reprod Toxicol. 2023 Jun;118:108360. doi: 10.1016/j.reprotox.2023.108360. Epub 2023 Mar 8. PMID: 36894038. 3: Chiriboga CA, Bruno C, Duong T, Fischer D, Mercuri E, Kirschner J, Kostera- Pruszczyk A, Jaber B, Gorni K, Kletzl H, Carruthers I, Martin C, Warren F, Scalco RS, Wagner KR, Muntoni F; JEWELFISH Study Group. Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study. Neurol Ther. 2023 Apr;12(2):543-557. doi: 10.1007/s40120-023-00444-1. Epub 2023 Feb 13. Erratum in: Neurol Ther. 2023 Oct;12(5):1799-1801. doi: 10.1007/s40120-023-00503-7. PMID: 36780114; PMCID: PMC9924181. 4: Kray KM, McGovern VL, Chugh D, Arnold WD, Burghes AHM. Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice. Neurobiol Dis. 2021 Nov;159:105488. doi: 10.1016/j.nbd.2021.105488. Epub 2021 Aug 20. PMID: 34425216; PMCID: PMC8502210. 5: Wadman RI, van der Pol WL, Bosboom WM, Asselman FL, van den Berg LH, Iannaccone ST, Vrancken AF. Drug treatment for spinal muscular atrophy types II and III. Cochrane Database Syst Rev. 2020 Jan 6;1(1):CD006282. doi: 10.1002/14651858.CD006282.pub5. PMID: 32006461; PMCID: PMC6995983. 6: Kletzl H, Marquet A, Günther A, Tang W, Heuberger J, Groeneveld GJ, Birkhoff W, Mercuri E, Lochmüller H, Wood C, Fischer D, Gerlach I, Heinig K, Bugawan T, Dziadek S, Kinch R, Czech C, Khwaja O. The oral splicing modifier RG7800 increases full length survival of motor neuron 2 mRNA and survival of motor neuron protein: Results from trials in healthy adults and patients with spinal muscular atrophy. Neuromuscul Disord. 2019 Jan;29(1):21-29. doi: 10.1016/j.nmd.2018.10.001. Epub 2018 Oct 30. PMID: 30553700. 7: Calder AN, Androphy EJ, Hodgetts KJ. Small Molecules in Development for the Treatment of Spinal Muscular Atrophy. J Med Chem. 2016 Nov 23;59(22):10067-10083. doi: 10.1021/acs.jmedchem.6b00670. Epub 2016 Aug 16. PMID: 27490705; PMCID: PMC5744254. 8: Ratni H, Karp GM, Weetall M, Naryshkin NA, Paushkin SV, Chen KS, McCarthy KD, Qi H, Turpoff A, Woll MG, Zhang X, Zhang N, Yang T, Dakka A, Vazirani P, Zhao X, Pinard E, Green L, David-Pierson P, Tuerck D, Poirier A, Muster W, Kirchner S, Mueller L, Gerlach I, Metzger F. Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy. J Med Chem. 2016 Jul 14;59(13):6086-100. doi: 10.1021/acs.jmedchem.6b00459. Epub 2016 Jul 6. PMID: 27299419.