JF-NP-26

JF-NP-26, an inactive photocaged derivative of raseglurant, is the first caged mGlu5 receptor negative allosteric modulator. Uncaging of JF-NP-26 is elicited with light pulses in the visible spectrum (405 nm). JF-NP-26 induces light-dependent analgesia in models of inflammatory and neuropathic pain in freely behaving animals.

Product information

CAS Number: 2341841-03-8

Molecular Weight: 513.56

Formula: C30H28FN3O4

Chemical Name: [7-(diethylamino)-2-oxo-2H-chromen-4-yl]methyl N-{2-[2-(3-fluorophenyl)ethynyl]-4,6-dimethylpyridin-3-yl}carbamate

Smiles: CC1C=C(C)N=C(C#CC2C=C(F)C=CC=2)C=1NC(=O)OCC1=CC(=O)OC2=CC(=CC=C21)N(CC)CC

InChiKey: XBUISHYVUXKBCO-UHFFFAOYSA-N

InChi: InChI=1S/C30H28FN3O4/c1-5-34(6-2)24-11-12-25-22(16-28(35)38-27(25)17-24)18-37-30(36)33-29-19(3)14-20(4)32-26(29)13-10-21-8-7-9-23(31)15-21/h7-9,11-12,14-17H,5-6,18H2,1-4H3,(H,33,36)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

The authors assessed the JF-NP-26-mediated negative allosteric modulation of mGlu5 receptor-induced responses to the orthosteric agonist quisqualate, by using an inositol phosphate (IP) accumulation assay. while JF-NP-26 didn’t show activity in dark conditions, its negative allosteric modulator (NAM) activity is rescued upon 405 nm visible light illumination (pIC50=7.1). Agonist challenge induced a robust mGlu5 receptor-mediated intracellular calcium rise both in dark and under 405 nm illumination, which was blocked by raseglurant. JF-NP-26 is unable to restrain agonist-mediated signalling in dark conditions, it abolished mGlu5 receptor-mediated intracellular calcium accumulation upon 405 nm irradiation, thus demonstrating a light-dependent negative allosteric modulator activity.

In Vivo:

JF-NP-26 (10 mg/kg; i.p.; irradiated at 405 nm (or dark) for 5 min) significantly increased pain thresholds in CCI mice only after thalamic irradiation. JF-NP-26 (10 mg/kg; i.p.; at 405 nm light (or dark) for 5 min) shows light-dependent analgesic efficacy in neuropathic pain. Systemic administration and in vivo photoactivation of JF-NP-26 does not impair memory in mouse.

Products are for research use only. Not for human use.