WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H526734
CAS#: 1449598-06-4
Description: 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.
Hodoodo Cat#: H526734
Name: RG7800
CAS#: 1449598-06-4
Chemical Formula: C24H28N6O
Exact Mass: 416.23
Molecular Weight: 416.530
Elemental Analysis: C, 69.21; H, 6.78; N, 20.18; O, 3.84
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.
| Biological target: | RG7800 is a SMN2 splicing modifier. |
| In vitro activity: | Compound 3 was shown to promote the inclusion of exon 7 in SMN2 mRNA, generating full-length (FL) mRNA in vitro using fibroblasts from an SMA type I patient (Figure 7A). To investigate SMN protein production as a consequence of splicing correction, an in vitro assay 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, compared to untreated controls, was similar in both cell types (60–80%; Figure 7B,C), suggesting that, in different cell types derived from SMA patients, compound 3 increases the SMN protein level as a result of correcting the dysfunctional SMN2 splicing in vitro. Reference: J Med Chem. 2016 Jul 14;59(13):6086-100. https://pubmed.ncbi.nlm.nih.gov/27299419/ |
| In vivo activity: | For assessment of the in vivo effects of compound 3 on SMN2 splicing, adult SMA model mice (C/C-allele) were treated for 10 days with vehicle or compound 3 (3 or 10 mg/kg po once daily). Compound 3 dose-dependently corrected SMN2 splicing by including exon 7 to create FL mRNA (Figure 8A), suggesting that compound 3 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 (Figure 8B). Reference: J Med Chem. 2016 Jul 14;59(13):6086-100. https://pubmed.ncbi.nlm.nih.gov/27299419/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 1.4 | 3.40 | |
| Ethanol | 2.5 | 6.00 |
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. |
| In vitro 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. |
| In vivo 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: Ratni H, Karp GM, Weetall M, Naryshkin NN, 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 (SMN2) splicing by small molecules: Discovery of a potential novel
medicine to treat spinal muscular atrophy. J Med Chem. 2016 Jun 14. [Epub ahead
of print] PubMed PMID: 27299419.
