General description
A sulfonamide compound that prevents melanopsin/Opn4 photoactivation in a reversible and cis-Retinal-competitive manner (Kb = 6 and 0.16 µM in competitive binding studies using Opn4 pre-bound with cis-Retinal or not) without apparent affinity toward bovine retina rhodopsin or a panel of 74 other receptors, ion channels, and enzymes. Effectively inhibits cellular phototransduction mediated by human Opn4 in CHO transfectants (IC50 = 665 nM; drug added 30 min before 10 µM 9-cis-Retinal & photoactivation), by murine Opn4 in transfected Xenopus oocytes (IC50 = 190 nM; drug added 3 min before 50 µM 11-cis-Retinal and photoactivation), as well as by endogenous Opn4 in primary rat ipRGCs (intrinsically photosensitive retinal ganglion cells; 10 µM). Shown to be bioavailable in mice via i.p. injection (retina [AA92593] ~7.5 µM 30 min post 30 mg/kg i.p. dosing; >95% clearance within 2 h) and effectively suppress PLR (pupillary light reflex; pupil constriction) in a time- and Opn4-dependent manner in mice in vivo. Likewise, blue light insensitivity is observed in Opn4-/- and AA92593-treated wild-type, but not vehicle-treated wild-type, P14 neonatal mice.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
melanopsin (Opn4)
Reversible: yes
Target Ki: 110 and 160 nM for human and mouse melanopsin, respectively)
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 monthst at -20°C.
Other Notes
Jones, K.A., et al. 2013. Nat. Chem. Biol.9, 630.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Regulatory Review (Z)
| assay | ≥98% (HPLC) |
| Quality Level | 100 |
| form | solid |
| manufacturer/tradename | Calbiochem® |
| storage condition | OK to freeze,protect from light |
| color | white |
| solubility | DMSO: 100 mg/mL |
| storage temp. | 2-8°C |
| SMILES string | [S](=O)(=O)(N2CCCCC2)c1cc(c(cc1)OC)C |
| InChI | 1S/C13H19NO3S/c1-11-10-12(6-7-13(11)17-2)18(15,16)14-8-4-3-5-9-14/h6-7,10H,3-5,8-9H2,1-2H3 |
| InChI key | HDTKLZINZGEPFG-UHFFFAOYSA-N |
