5.09267

Opn4 Antagonist

• Synonyme(s) : Opn4 Antagonist, Opn4 Antagonist, Opsinamide, Melanopsin-inhibiting Sulfonamide AA92593, 1-(4-Methoxy-3-methyl-benzenesulfonyl)piperidine, 1-(4-Methoxy-3-methylphenylsulfonyl)piperidine, Melanopsin Antagonist, Opsinamide AA92593
• Formule empirique (notation de Hill): C₁₃H₁₉NO₃S
• Numéro CAS: 457961-34-1
• Poids moléculaire : 269.36
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• Pureté: ≥98% (HPLC)
• Niveau de qualité: 100
• Forme: solid
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: white
• Solubilité: DMSO: 100 mg/mL
• Température de stockage: 2-8°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
• Clé InChI: HDTKLZINZGEPFG-UHFFFAOYSA-N

Description

Description générale

A sulfonamide compound that prevents melanopsin/Opn4 photoactivation in a reversible and cis-Retinal-competitive manner (K_b = 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.

A sulfonamide compound that prevents melanopsin/Opn4 photoactivation in a reversible and cis-Retinal-competitive manner 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 (IC₅₀ = 665 nM; using CHO transfectants), murine Opn4 (IC₅₀ = 190 nM; using transfected Xenopus oocytes), and rat Opn4 (10 µM; using primary rat ipRGCs). Shown to effectively suppress PLR (pupillary light reflex; pupil constriction) in a time- and Opn4-dependent manner in mice (30 mg/kg i.p.) in vivo. Likewise, blue light insensitivity is observed in Opn4^-/- and AA92593-treated wild-type, but not vehicle-treated wild-type, P14 neonatal mice.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
melanopsin (Opn4)

Reversible: yes

Target K_i: 110 and 160 nM for human and mouse melanopsin, respectively)

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Regulatory Review (Z)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 monthst at -20°C.

Autres remarques

Jones, K.A., et al. 2013. Nat. Chem. Biol.9, 630.

Informations légales

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informations sur la sécurité

• Code de la classe de stockage: 13 - Non Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable