SML2448

PK4C9

≥98% (HPLC)

• Synonym(s): Homocarbonyltopsentin, [2-[(6-Hydroxy-1H-indol-3-yl)carbonyl]-1H-imidazol-4-yl]-1H-indol-3-yl--methanone
• Empirical Formula (Hill Notation): C₂₁H₁₄N₄O₃
• CAS Number: 172286-77-0
• Molecular Weight: 370.36
• UNSPSC Code: 12352200
• NACRES: NA.77
• Assay: ≥98% (HPLC)
• Form: powder

Properties

• assay: ≥98% (HPLC)
• form: powder
• color: white to very dark brown
• solubility: DMSO: 2 mg/mL, clear
• 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

Description

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.

Safety Information

• Storage Class: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable