Biochem/physiol Actions
PK4C9 is a splice modulator of survival of motor neuron gene SMN2 that increases production of full-length SMN protein. Spinal muscular atrophy (SMA) is a motor neuron disease caused by deficiency in SMN protein resulting from loss of expression of the SMN1 gene. The related SMN2 gene can compensate, but polymorphism in SMN2 often results in altered splicing and exclusion of exon 7, which is required for a full-length SMN transcript. PK4C9 binds to pentaloop conformations of the stem-loop RNA structure TSL2, a cis-regulatory element for E7 inclusion, and promotes a shift to triloop conformations that display enhanced E7 splicing. In SMA cells, PK4C9 increased E7 inclusion by 40% accompanied by a 1.5-fold increase in SMN protein, a level shown to reverse SMA phenotypes in mice models.
Splice modulator of survival of motor neuron gene SMN2 that increases production of full-length SMN protein.
| assay | ≥98% (HPLC) |
| form | powder |
| color | white to very dark brown |
| solubility | DMSO: 2 mg/mL, clear |
| web metadata keyword.default | 172286-77-0 PK4C9,Homocarbonyltopsentin for spinal muscular atrophy,Homocarbonyltopsentin,PK4C9 chemical structure and applications,PK4C9 exon 7 inclusion agent,PK4C9 for laboratory use,PK4C9 for research,PK4C9 full-length SMN protein modulator,PK4C9 motor neuron disease treatment,PK4C9 splice modulation for SMA,PK4C9 splice modulator,Sigma-Aldrich PK4C9,[2-[(6-Hydroxy-1H-indol-3-yl)carbonyl]-1H-imidazol-4-yl]-1H-indol-3-yl--methanone,research-grade PK4C9 |
| storage temp. | 2-8°C |
| SMILES string | [nH]1c(nc(c1)C(=O)c4c5c([nH]c4)cccc5)C(=O)c2c3c([nH]c2)cc(cc3)O |
| InChI | 1S/C21H14N4O3/c26-11-5-6-13-15(9-23-17(13)7-11)20(28)21-24-10-18(25-21)19(27)14-8-22-16-4-2-1-3-12(14)16/h1-10,22-23,26H,(H,24,25) |
| InChI key | DRCVQVIMGSWRLN-UHFFFAOYSA-N |
