The primary targets are AMPA‑type glutamate receptors (AMPARs) and kainate‑type glutamate receptors (KARs). For AMPAR, the IC₅₀ is 190 nM, and the functional efficacy (IC₅₀) on native AMPA receptors in rat cortical wedges is 0.46 µM.
For KAR, the functional efficacy (IC₅₀) on native kainate receptors in rat cortical wedges is 0.42 µM.
For NMDA receptors, the functional efficacy is >30 µM, indicating little affinity. No Ki or EC₅₀ values were reported. [2]
Selurampanel targets the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, a subtype of ionotropic glutamate receptor. As a competitive antagonist, Selurampanel binds to the glutamate-binding site on the AMPA receptor, preventing glutamate from activating the receptor. This inhibition reduces excitatory neurotransmission and can prevent excessive neuronal firing associated with seizures and other neurological conditions. The compound's IC50 of 190 nM indicates potent antagonism. Its reasonable blood-brain barrier penetration enables central nervous system activity.

Selurampanel is a competitive AMPAR antagonist that binds within the glutamate cleft of the extracellular domain of the receptor, blocking the clamshell‑like closure necessary for pore opening, as demonstrated crystallographically for the GluA2 tetramer.
It has an IC₅₀ of 190 nM for the AMPAR and also shows antagonist activity at KAR sites.
The compound is quite selective for AMPARs and KARs, with little affinity for NMDA receptors (functional efficacy >30 µM for NMDA).
The IC₅₀ for 150 other molecular targets was >10 µM, suggesting a low likelihood of unwanted central nervous system effects.
It acts by directly competing with glutamate for the receptor binding site, unlike noncompetitive antagonists that bind to allosteric sites. [2]
In vitro, Selurampanel demonstrates potent and competitive antagonism of AMPA receptors with an IC50 of 190 nM. In electrophysiological assays using neurons or cells expressing recombinant AMPA receptors, the compound produces concentration-dependent inhibition of AMPA-evoked currents. Selurampanel shows selectivity for AMPA receptors over kainate and NMDA receptors, though the extent of selectivity has not been fully characterized. The compound's competitive mechanism is confirmed by the observation that its inhibition can be overcome by increasing glutamate concentrations.

Selurampanel (Compound 1S) efficiently and dose-dependently inhibits generalized tonic-clonic seizures caused by maximal electroshock seizure (MES) in mice, with an ED50 value of about 7 mg/kg after 1 hour of pretreatment [1]. The mouse plasma half-life was found to be 3.3 hours in a research involving an intravenous dosage of 3 mg/kg. It also had a low clearance of 5.4 mL/min▯kg and a medium volume of distribution (Vdss=1.3 L/kg).
In the mouse maximal electroshock seizure (MES) model, Selurampanel showed an oral ED₅₀ of 6 mg/kg.
It was also effective in the DBA/2 audiogenic seizure mouse model, the pentylenetetrazole‑induced seizure model, and the WAG/Rij rat model (which is predictive of anti‑absence activity).
Efficacy against kindling suggests potential action against human complex partial (dyscognitive) seizures.
In a photosensitive epilepsy trial (single doses of 15, 50, and 100 mg), 9 out of 13 subjects had complete suppression of the photoparoxysmal response (PPR) for 2 to 32 hours, with some reduction in all actively treated subjects.
In an inpatient presurgical trial (75 or 150 mg/day in three divided doses for 9 days), Selurampanel reduced seizure rate by about 50% compared to placebo (drug 0.59/day, 90% CI: 0.35‑1.02 vs placebo 1.22/day, 90% CI: 0.73‑2.04). Complex partial seizures were reduced comparatively more than secondarily generalized tonic‑clonic seizures.
In a 12‑week double‑blind adjunctive therapy trial for refractory partial‑onset seizures (300 and 450 mg/day), the mean percentage change from baseline was 39% for 450 mg/day (n=44), 22% for 300 mg/day (n=24), and 24% for placebo (n=25). Median percentage changes were 30% (450 mg/day), 33.4% (300 mg/day), and 14.3% (placebo). The primary endpoint did not reach statistical significance (adjusted p values 0.083‑0.099).
In an open‑label extension (up to 30 weeks), responder rates (≥50% seizure reduction) reached 46% during weeks 14‑26. [2]
In vivo, Selurampanel has demonstrated anticonvulsant activity in animal models of epilepsy. Administration of the compound reduces seizure frequency and severity in various seizure models, including maximal electroshock, pentylenetetrazole-induced, and kindling models. Its reasonable blood-brain barrier penetration enables central nervous system activity following oral administration. The compound has been evaluated in clinical trials for epilepsy, though development may have been limited. Its anticonvulsant effects are attributed to AMPA receptor antagonism and reduction of excitatory neurotransmission.

Radioligand binding assays were performed using rat whole‑brain membranes. [³H]CNQX was used to assess affinity at the AMPA receptor; [³H]HCGP39653 and [³H]HMDL105519 were used for NMDA receptor glutamate and glycine sites, respectively; [³H]kainate was used for kainate receptor binding. IC₅₀ values were calculated using GraphPad Prism software. Data are geometric means of at least three independent experiments. [1]
In vitro enzyme/receptor binding assays for Selurampanel typically involve radioligand binding studies using membrane preparations from brain tissue or cells expressing recombinant AMPA receptors. [³H]-AMPA or other labeled AMPA receptor ligands are used to measure competitive displacement by Selurampanel. The compound is incubated with membrane preparations and labeled ligand, and bound radioactivity is measured after filtration. Binding affinity (Ki) is calculated from competition curves. Alternatively, electrophysiological patch-clamp recordings are used to assess functional antagonism of AMPA-evoked currents.

(1) hERG cell‑based assay: Selurampanel showed an IC₅₀ > 30 μM, indicating low risk of hERG interaction. [1]
(2) CYP450 inhibition assay: Selurampanel showed no substantial inhibition of all tested cytochrome P450 isoforms up to 10 μM. [1]
In vitro cellular assays for Selurampanel utilize primary neurons, brain slices, or cell lines expressing recombinant AMPA receptors. Whole-cell patch-clamp electrophysiology is the primary method for assessing compound activity. Neurons are voltage-clamped, and AMPA-evoked currents are elicited by rapid application of glutamate or AMPA. Selurampanel is applied at concentrations ranging from 0.1 nM to 10 µM, and the percentage of current inhibition is calculated. IC50 values are determined from concentration-response curves. Neuroprotective effects may be assessed in models of excitotoxicity.

Preclinical efficacy studies were conducted in mouse models including the maximal electroshock seizure (MES) model, the DBA/2 audiogenic seizure model, the pentylenetetrazole‑induced seizure model, and the WAG/Rij rat model. In the MES model, the oral ED₅₀ was determined to be 6 mg/kg. Details on formulation, administration route, and dosing volume were not provided in this review. [2]
In vivo animal experiments for Selurampanel typically involve rodent models of epilepsy. The compound is administered orally or intraperitoneally at doses ranging from 1 to 30 mg/kg. In maximal electroshock seizure tests, seizure protection is assessed by the absence of hindlimb extension. In pentylenetetrazole-induced seizure models, the latency to seizure onset and seizure severity are recorded. In kindling models, the effects on seizure progression are evaluated. The compound's brain penetration is confirmed by measuring brain concentrations.

Preclinical data showed considerable interspecies differences in oral absorption, clearance, and volume of distribution, although a rapid Tₘₐₓ of 0.5‑1 hour was observed in three different species.
Protein binding in mammals was moderate, ranging from 75‑88%.
No cytochrome P450 induction or inhibition was observed.
In humans, after a single dose, Tₘₐₓ was about 3 hours (measured in the photosensitive epilepsy study). Drug exposure versus dose was relatively linear for doses of 15, 50, and 100 mg.
During the inpatient trial (after 3, 6, and 9 days of treatment), Tₘₐₓ ranged from 1.25 to 3.22 hours, and the area under the curve (AUC) was linear; exposure to a 50 mg morning dose was approximately double that of a 25 mg morning dose.
Oral bioavailability is reported to be good, with reasonable blood‑brain barrier penetration. [2]
Selurampanel exhibits oral bioavailability and reasonable blood-brain barrier penetration. Following oral administration, the compound achieves therapeutic concentrations in plasma and brain. Pharmacokinetic parameters including Cmax, Tmax, AUC, and half-life have been characterized. The compound's brain-to-plasma ratio supports its use for central nervous system indications. Its metabolism and elimination pathways have been studied. The compound's pharmacokinetic profile supports oral dosing for epilepsy treatment.

Preclinical safety studies showed no indication of cardiotoxicity, reproductive toxicity, or genotoxicity, and no protein adduct formation occurred.
In clinical trials, the most common treatment‑emergent adverse effects were dizziness and somnolence. In the 12‑week double‑blind study, dizziness occurred in 31.8% (450 mg/day), 12.5% (300 mg/day), and 4.0% (placebo); somnolence occurred in 15.9% (450 mg/day), 4.2% (300 mg/day), and 4.0% (placebo). Fatigue, confusion, vertigo, and gait disturbance were also reported at lower rates.
Discontinuation rates in the 10‑week outpatient trial were 15.9% (450 mg/day), 16.7% (300 mg/day), and 4% (placebo). In the open‑label extension, 15.7% dropped out, with 5.9% attributed to adverse events.
No deaths were reported among 110 clinical trial participants. No serious adverse events were reported in the short‑term trials; one SAE (nature unspecified) occurred in the open‑label phase.
No rashes or allergic reactions were reported. One patient discontinued the 450 mg/day dose due to irritability; psychiatric disorders were reported in 5.9% of open‑label patients.
No cardiotoxicity, reproductive toxicity, or genotoxicity signals were observed in preclinical studies. [2]
Preclinical toxicology studies of Selurampanel have demonstrated an acceptable safety profile. In animal studies, the compound was generally well-tolerated at therapeutic doses. Common adverse effects were consistent with AMPA receptor antagonism and included sedation and motor impairment at high doses. No significant organ toxicity was observed. The compound's safety profile supports its evaluation for epilepsy. However, comprehensive toxicology data are limited in the public domain.

[1]. Design and Synthesis of Selurampanel, a Novel Orally Active and Competitive AMPA Receptor Antagonist. ChemMedChem. 2017 Feb 3;12(3):197-201.

[2]. BGG492 (selurampanel), an AMPA/kainate receptor antagonist drug for epilepsy. Expert Opin Investig Drugs. 2014 Jan;23(1):107-13.

Selurampanel has been studied in adrenocortical adenomas and sarcomas, and endometrial stromal tumors.

---

Selurampanel (BGG492, CAS# 912574‑69‑7) is a competitive AMPA/kainate receptor antagonist under development for epilepsy. It is a quinazolinedione sulfonamide derivative with good oral bioavailability and reasonable blood‑brain barrier penetration. The compound has been studied in Phase II clinical trials for photosensitive epilepsy, presurgical evaluation of partial seizures, and as adjunctive therapy for refractory partial‑onset seizures.
The mechanism involves binding within the glutamate cleft of the AMPA receptor extracellular domain, blocking the conformational change required for ion channel opening. It also has antagonist activity at kainate receptors, though the relevance to antiepileptic effect is unknown.
In clinical trials, the drug was administered orally at doses ranging from 15 mg to 450 mg per day, typically in divided doses (e.g., three times daily). Efficacy was modest, with median seizure reduction of 30‑33.4% at higher doses versus 14.3% for placebo in one trial, though the primary endpoint was not met.
The most common adverse effects are dizziness and somnolence, typical of AMPAR antagonists. Tolerability appears reasonably good, with discontinuation rates similar to other antiepileptic drugs.
The drug has not been approved; development may be limited due to the availability of perampanel (a noncompetitive AMPAR antagonist) and modest efficacy signals.
No FDA warnings or clinical use information are mentioned. [2]
Selurampanel (BGG 492) is an orally active, competitive AMPA receptor antagonist with an IC50 of 190 nM. It has a molecular formula of C16H19N5O4S and a molecular weight of 377.42 g/mol. The compound demonstrates reasonable blood-brain barrier penetration and has been evaluated for the treatment of epilepsy. Selurampanel is used in research as an AMPA receptor antagonist tool compound.

C16H19N5O4S

377.41816

377.115

912574-69-7

45381907

White to off-white solid powder

1

2

6

4

26

677

0

MCECSFFXUPEPDB-UHFFFAOYSA-N

InChI=1S/C16H19N5O4S/c1-9(2)10-8-13-12(7-11(10)14-5-6-17-20(14)3)15(22)21(16(23)18-13)19-26(4,24)25/h5-9,19H,1-4H3,(H,18,23)

N-[6-(2-methylpyrazol-3-yl)-2,4-dioxo-7-propan-2-yl-1H-quinazolin-3-yl]methanesulfonamide

BGG492 BGG-492 BGG 492

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)