2. Membrane Transporter/Ion Channel Neuronal Signaling GPCR/G Protein MAPK/ERK Pathway Stem Cell/Wnt Epigenetics
  3. nAChR 5-HT Receptor ERK Epigenetic Reader Domain
  4. A-582941

A-582941 is a selective, orally active, blood-brain barrier-permeable α7 nAChR agonist, with Ki values of 10.8 nM and 17 nM in rat brain and human frontal cortex, respectively. A-582941 exhibits agonistic activity at 5-HT3 receptors, with a Ki of 150 nM. A-582941 triggers phosphorylation of ERK1/2 and CREB, inhibits GSK-3β via Ser-9 phosphorylation, increases acetylcholine release, induces the expression of Arc and c-Fos, activates brain regions associated with working memory and attention, and reduces cell death caused by nerve growth factor (NGF) deprivation. A-582941 is applicable for the research of Alzheimer's disease and schizophrenia.

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A-582941

A-582941 Chemical Structure

CAS No. : 848591-89-9

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Description

A-582941 is a selective, orally active, blood-brain barrier-permeable α7 nAChR agonist, with Ki values of 10.8 nM and 17 nM in rat brain and human frontal cortex, respectively. A-582941 exhibits agonistic activity at 5-HT3 receptors, with a Ki of 150 nM. A-582941 triggers phosphorylation of ERK1/2 and CREB, inhibits GSK-3β via Ser-9 phosphorylation, increases acetylcholine release, induces the expression of Arc and c-Fos, activates brain regions associated with working memory and attention, and reduces cell death caused by nerve growth factor (NGF) deprivation. A-582941 is applicable for the research of Alzheimer's disease and schizophrenia[1][2][3].

IC50 & Target[1]

5-HT3 Receptor

150 nM (Ki)

In Vitro

A-582941 binds with high affinity to α7 nAChRs in rat brain (Ki = 10.8 nM) and human frontal cortex (Ki = 17 nM) membranes, with slightly lower affinity for antagonist-labeled α7 nAChRs (Ki = 88 nM) in rat brain[1].
A-582941 acts as a partial agonist at recombinant human α7 nAChRs in Xenopus oocytes, with an EC50 of 4260 nM and 52% efficacy relative to acetylcholine[1].
A-582941 acts as a partial agonist at recombinant rat α7 nAChRs in Xenopus oocytes, with an EC50 of 2450 nM and 60% efficacy relative to acetylcholine[1].
A-582941 (3 μM PNU-120596 pre-incubated prior to treatment) exhibits increased potency (EC50 = 580 nM) and efficacy (207% relative to acetylcholine) at recombinant human α7 nAChRs in Xenopus oocytes[1].
A-582941 increases ERK1/2 phosphorylation in α7 nAChR-expressing PC12 cells with an EC50 of 95 nM, an effect mediated by α7 nAChRs[1].
A-582941 (0.1-100 μM) protects PC12 cells from NGF withdrawal-induced cell death[1].
A-582941 (100 nM-10,000 nM; 9 days) does not induce proliferation in cultured human keratinocytes[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

A-582941 Related Antibodies

Cell Proliferation Assay[1]

Cell Line: Cultured human keratinocytes
Concentration: 100 nM, 10,000 nM
Incubation Time: 9 days, with medium refreshed every 3-4 days
Result: Produced no detectable proliferation under conditions where serum/growth factor supplements evoked significant proliferative events.
Parmacokinetics
Species Dose Route T1/2 Vss CLplasma Cmax Bioavailability
Mice[1] 1.0 μmol/Kg i.v. 1.4 h 11.4 L/kg 7.9 L/h/kg / /
Mice[1] 1.0 μmol/Kg p.o. / / / 18 ng/mL ~100 %
Rat[1] 6.2 μmol/Kg i.v. 1.5 h 9.2 L/kg 4.7 L/h/kg / /
Rat[1] 6.2 μmol/Kg p.o. / / / 114 ng/mL 90 %
Dog[1] 0.5 μmol/Kg i.v. 1.4 h 7.9 L/kg 5.3 L/h/kg / /
Dog[1] 3.0 μmol/Kg p.o. / / / 79 ng/mL 22 %
Monkey[1] 0.5 μmol/Kg i.v. 2.0 h 3.9 L/kg 1.6 L/h/kg / /
Monkey[1] 3.0 μmol/Kg p.o. / / / 39 ng/mL 50 %
In Vivo

A-582941 (0.01-1.00 μmol/kg; i.p.) dose-dependently increases ERK1/2 and CREB phosphorylation in mouse brain regions involved in cognition[1].
A-582941 (0.01-1.00 μmol/kg; i.p.) improves memory consolidation in mice, with full efficacy achieved at 0.1 μmol/kg (i.p.)[1].
A-582941 (0.1-1.0 μmol/kg; i.p.) dose-dependently increases Ser-9 GSK-3β phosphorylation in the mouse cingulate cortex[1].
A-582941 (0.1-1.0 μmol/kg; i.p.) improves short-term recognition memory in rats, with full efficacy achieved at 0.1 μmol/kg (i.p.)[1].
A-582941 (3 μmol/kg; i.p.; once daily; 3 consecutive days) moderately increases medial prefrontal cortex acetylcholine release in freely moving rats[1].
A-582941 (1.8 μmol/kg/day; s.c.; continuous infusion; 7 days) maintains efficacy in improving rat short-term recognition memory[1].
A-582941 (0.003-0.100 μmol/kg; i.m.) improves working memory in young Rhesus monkeys, with full efficacy achieved at 0.01 μmol/kg (i.m.)[1].
A-582941 (10 μmol/kg; i.p.) reverses MLA (HY-N2332)-induced sensory gating deficit in rats[1].
A-582941 (3-10 μmol/kg; i.p.) improves genetic sensory gating deficit in DBA/2J mice, with efficacy retained after 5 consecutive days of 3 μmol/kg (i.p.) dosing[1].
A-582941 (0.1-1.0 μmol/kg; s.c.) modestly improves response inhibition/impulsivity in spontaneously hypertensive rat pups[1].
A-582941 (0.1-10 mg/kg; s.c.; single dose) induces dose-dependent increases in Arc and c-Fos mRNA and protein expression in limbic forebrain regions of juvenile male Wistar rats, with maximal effects at 10 mg/kg and greater responsiveness observed in juvenile compared to adult rats[2].
A-582941 (0.1-10 mg/kg; s.c.; single dose) increases Arc and c-Fos immunoreactive cell counts in limbic forebrain regions of adult male Wistar rats at 10 mg/kg, but does not induce measurable increases in Arc or c-Fos mRNA expression in any examined region[2].
A-582941 (1.14-38 μg/kg; i.m.; single dose) significantly improves delayed matching-to-sample task accuracy in young adult Rhesus monkeys, with a 22.2% increase in long delay trial accuracy (twice the magnitude of improvement in short delay trials) that is not sustained 24 hours after dosing[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: unspecified strain[1]
Dosage: 1.8 μmol/kg/day
Administration: s.c.; continuous infusion; 7 days
Result: Maintained efficacy in the social recognition test, as reflected by a reduced ratio of investigative behavior during the second session (T2) compared to the first session (T1).
Reached a mean steady-state plasma concentration of 3.1 ± 0.3 ng/mL (11 nM).
Animal Model: DBA/2J[1]
Dosage: 3 μmol/kg (acute; 5-day repeated dosing); 10 μmol/kg (acute)
Administration: i.p.; acute; once daily; 5 consecutive days
Result: Significantly improved sensory gating in acutely treated mice.
Retained efficacy after 5 consecutive days of dosing with 3 μmol/kg (i.p.).
Reached an average plasma concentration of 44 ng/mL (157 nM) after 5 days of repeated dosing.
Animal Model: Wistar rats (adult, male, approximately 55 days, 210-230 g)[2]
Dosage: 0.1, 0.3, 1, 3 and 10 mg/kg
Administration: s.c.; single dose
Result: Did not induce significant increases in Arc or c-Fos mRNA expression in any brain region examined (mPFC, VO/LO cortex, hippocampus).
Increased Arc immunoreactive cell counts at 10 mg/kg in the mPFC (262% increase vs controls), VO/LO cortex (233% increase vs controls), ACCshell (851% increase vs controls), and dmSTR (419% increase vs controls); no significant effect was seen in the ACCcore or dlSTR.
Increased c-Fos immunoreactive cell counts at 10 mg/kg in the mPFC (97% increase vs controls), VO/LO cortex (115% increase vs controls), and ACCshell (169% increase vs controls); no significant effect was seen in the ACCcore, dmSTR, or dlSTR.
Animal Model: Macaca mulatta (male, 9-18 years old, 7.2-11.8 kg)[3]
Dosage: 1.14 μg/kg; 3.8 μg/kg; 11.4 μg/kg; 38 μg/kg
Administration: i.m.; single dose
Result: Significantly improved delayed matching-to-sample (DMTS) task accuracies relative to vehicle controls.
Produced a significant increase in short delay trial accuracy at 11.4 μg/kg dose.
Produced significant increases in long delay trial accuracy at 1.14 μg/kg, 3.8 μg/kg, and 11.4 μg/kg doses.
Increased long delay trial accuracy by 22.2% above control, approximately twice the 11.3% increase observed in short delay trials.
Showed a non-significant trend toward improved accuracy at 38 μg/kg dose.
Produced no statistically significant improvement in task accuracies during sessions initiated 24 hours after dosing, despite mean long delay accuracies remaining above vehicle levels.
Produced no significant effect on sample or choice task latencies.
Molecular Weight

280.38

Formula

C17H20N4
CAS No.
SMILES

N=1N=C(C=CC1C=2C=CC=CC2)N3CC4CN(C)CC4C3
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

A-582941848591-89-9A582941A 582941nAChR5-HT ReceptorERKEpigenetic Reader DomainNicotinic acetylcholine receptorsSerotonin Receptor5-hydroxytryptamine ReceptorExtracellular signal regulated kinasesacetylcholinehuman α7 nAChRalzheimer diseaseGSK-3βCREBERK1/2rat α7 nAChRschizophrenia5-HT3 receptorα7 neuronal nicotinic acetylcholine receptorInhibitorinhibitorinhibit

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