(S)-(-)-5-Fluorowillardiine - CAS 140187-23-1
Catalog number: 140187-23-1
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
Molecular Weight:
A more potent and selective AMPA receptor agonist (at hGluR1 and hGluR2) than AMPA itself (Ki = 14.7, 25.1, and 1820 nM for hGluR1, hGluR2 and hGluR5 respectively).
(5S)-Fluorowillardiine; (S)-5-Fluorowillardiine
Canonical SMILES:
1.(S)-5-fluorowillardiine-mediated neurotoxicity in cultured murine cortical neurones occurs via AMPA and kainate receptors.
Larm JA;Cheung NS;Beart PM Eur J Pharmacol. 1996 Oct 24;314(1-2):249-54.
We have examined the neurotoxic effects of kainate, (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and the novel AMPA-receptor preferring agonist (S)-5-fluorowillardiine in murine cultured cortical neurones. Kainate induced > 90% cell death (EC50 65 microM) and (S)-AMPA only about 50% cell death (EC50 3.1 microM), both in a monophasic dose-dependent manner. (S)-5-Fluorowillardiine also killed > 90% of neurones, however, in a biphasic dose-dependent manner (EC50 0.70 and 170 microM). Additionally, the neurotoxic effects of (S)-AMPA and (S)-5-fluorowillardiine (high-affinity component) were attenuated by the AMPA receptor antagonists LY293558 ((3,S,4aR, 6R,8aR)-6[2h91 H-tetrazol-5-yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinol ine- 3-carboxylic acid). A component of kainate and (S)-5-fluorowillardiine (low-affinity component) neurotoxicity was blocked by the low-affinity kainate receptor antagonist NS-102 (5-nitro-6,7,8,9-tetrahydrobenzo[g]indole-2,3-dione-3-oxime). We have shown that both kainate and (S)-AMPA can effect substantial cell death in cortical neurones and that the novel agonist (S)-5-fluorowillardiine exerts its excitotoxicity through both AMPA- and kainate-preferring receptors.
2.Mutant cycle analysis of the active and desensitized states of an AMPA receptor induced by willardiines.
Kizelsztein P;Eisenstein M;Strutz N;Hollmann M;Teichberg VI Biochemistry. 2000 Oct 24;39(42):12819-27.
The halogenated willardiines are agonists at the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of glutamate receptors. Although they differ only by the nature of the halogen substituent, they display marked differences in their efficacy to activate the receptor channel opening and in causing desensitization. We have studied the origin of the different agonist properties of the willardiines and in particular the nature of the structural element within the receptor binding domain that is able to distinguish between willardiines at a subatomic resolution of 0.6 A (the difference in radius between F and Br) and allow (S)-5-fluorowillardiine to cause receptor desensitization much more than (S)-5-bromowillardiine. For this purpose, we analyzed, with the thermodynamic mutant cycle method, the active and desensitized states induced by the willardiines in the GluR1 subtype of AMPA receptors and GluR1 mutants in which residues E398, Y446, L646, and S650, within the agonist binding domain, were mutated. The results were used to generate a 3D model of the willardiine docking mode. We suggest that the active and desensitized states of the AMPA-R correspond, respectively, to the open-lobe and closed-lobe conformations of the agonist binding domain.
3.Activation and desensitization of AMPA/kainate receptors by novel derivatives of willardiine.
Patneau DK;Mayer ML;Jane DE;Watkins JC J Neurosci. 1992 Feb;12(2):595-606.
Willardiine [(S)-1-(2-amino-2-carboxyethyl)pyrimidine-2,4-dione] is a naturally occurring heterocyclic excitatory amino acid present in the seeds of Acacia and Mimosa. A series of 5-substituted willardiines were synthesized in single enantiomeric forms and tested for activity at AMPA/kainate receptors, using whole-cell recording from mouse embryonic hippocampal neurons. The (S)- but not (R)-isomers of willardiine and 5-bromowillardiine were potent agonists, producing rapidly but incompletely desensitizing responses. At equilibrium, (S)-5-fluorowillardiine (EC50, 1.5 microM) was seven times more potent than (R,S)-AMPA (EC50, 11 microM) and 30 times more potent than willardiine (EC50, 45 microM); the potency sequence was fluoro greater than nitro greater than chloro approximately bromo greater than iodo greater than willardiine. Willardiines produce strikingly different degrees of desensitization: at saturating doses the equilibrium response to the weakly desensitizing agonist (S)-5-iodowillardiine was similar in amplitude to the response to kainate and 10 times larger than the response to the strongly desensitizing agonist (S)-willardiine. The desensitization sequence was fluoro greater than willardiine greater than nitro approximately chloro greater than bromo greater than iodo greater than kainate.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related AMPAR Products

CAS 154652-83-2 Tezampanel

(CAS: 154652-83-2)

Tezampanel, a decahydroisoquinoline derivative, has been found to be AMPA receptor as well as Kainic acid receptor antagonist that could probably be useful in s...

CAS 77472-70-9 4-Phenyl-2-pyrrolidone-1-acetamide

(CAS: 77472-70-9)

4-Phenyl-2-pyrrolidone-1-acetamide is a GABA derivative that exhibited apparent immunocorrection properties during immunosuppression induced by cyclophosphamide...

CAS 122306-11-0 Naspm

(CAS: 122306-11-0)

A poliamine amide as potent Spermidine uptake inhibitor.

CAS 161605-73-8 ZK200775

(CAS: 161605-73-8)

Competitive AMPA/kainate antagonist. In rat cortical membranes, displays high affinity for [3H]-AMPA (Ki = 120 nM) and [3H]-CNQX (Ki = 32 nM) binding sites and ...

CAS 83643-88-3 (S)-AMPA

(CAS: 83643-88-3)

(S)-AMPA is an active enantiomer of AMPA, which has been found to be a definitive agonist of the AMPA glutamatergic ionotropic receptor.

CAS 154164-30-4 YM 90K hydrochloride

YM 90K hydrochloride
(CAS: 154164-30-4)

YM 90K hydrochloride is a selective AMPA receptor antagonist (Ki = 84, 2200 and > 37000 nM for AMPA, kainate and NMDA receptors, respectively). YM 90K hydrochlo...

CAS 118876-58-7 NBQX

(CAS: 118876-58-7)

This active molecular is an AMPA receptor antagonist which blocks AMPA receptors in 10-20µM concentrations. It is also a Glutamate receptor antagonist. NBQX was...

CAS 141286-78-4 PEPA

(CAS: 141286-78-4)

2,6-Difluoro-4-[2-(phenylsul­fonyl­amino)­ethyl­thio]­phenoxy­acet­amide is a structurally novel, selective, high affinity AMPA ionotropic glutamate receptor ag...

Chemical Structure

CAS 140187-23-1 (S)-(-)-5-Fluorowillardiine

Quick Inquiry

Verification code

Featured Items