| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
- BK channels (Ki = 13 nM; exhibited closed-channel block with minimal open-channel block effect) [1]
- Sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) (IC50 = 1.2 μM; inhibited ATP hydrolysis and Ca²⁺ transport activity of SERCA) [2] - BK channels (acted as a BK-channel antagonist) [3] |
|---|---|
| ln Vitro |
- In recombinant BK channels (expressed in HEK293 cells) and native BK channels (from rat pituitary GH3 cells), Paxilline inhibited channel activity via an almost exclusively closed-channel block mechanism. It reduced the open probability of BK channels, prolonged the closed-state duration, and had minimal effect on open-channel conductance; the blocking effect was concentration-dependent with a Ki of 13 nM [1]
- In purified SERCA (from rabbit skeletal muscle sarcoplasmic reticulum) and SERCA-containing microsomal vesicles, Paxilline inhibited SERCA activity. It suppressed ATP hydrolysis by SERCA (IC50 = 1.2 μM) and reduced Ca²⁺ uptake into microsomal vesicles; the inhibition was non-competitive with respect to ATP and Ca²⁺, and did not disrupt the SERCA structure [2] - In primary cultures of rat hippocampal neurons, Paxilline (1-10 μM) reduced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and increased the amplitude of action potentials. It also inhibited BK channel-mediated afterhyperpolarization (AHP) in neurons, which was consistent with its BK-channel antagonist property [3] |
| ln Vivo |
- In adult male Sprague-Dawley rats, Paxilline exhibited anticonvulsant effects in two seizure models. 1) In the maximal electroshock seizure (MES) model: Intraperitoneal (i.p.) injection of Paxilline (1-10 mg/kg) dose-dependently increased the seizure threshold and reduced the duration of tonic hindlimb extension; the ED50 for MES was 3.2 mg/kg. 2) In the pentylenetetrazole (PTZ)-induced seizure model: I.p. injection of Paxilline (3-30 mg/kg) dose-dependently delayed the onset of myoclonic seizures and reduced the seizure severity; the ED50 for PTZ was 12.5 mg/kg. No neurotoxicity (assessed by rotorod test) was observed at doses up to 30 mg/kg [3]
|
| Enzyme Assay |
- For BK channel activity assay (recombinant/native channels): BK channels were expressed in HEK293 cells or isolated from rat GH3 cells, and patch-clamp recordings (whole-cell and inside-out patch configurations) were performed. Paxilline was applied to the intracellular side of the channel at concentrations ranging from 1 nM to 1 μM. Channel open probability, closed-state duration, and conductance were measured at different membrane potentials (from -80 mV to +80 mV) to evaluate the blocking effect; data were analyzed using patch-clamp analysis software to calculate Ki [1]
- For SERCA activity assay: Purified SERCA or microsomal vesicles were incubated with Paxilline (0.1-10 μM) in reaction buffers containing ATP and Ca²⁺. ATP hydrolysis activity was measured by detecting inorganic phosphate (Pi) release using a colorimetric assay. Ca²⁺ transport activity was assessed by monitoring the uptake of radioactive ⁴⁵Ca²⁺ into microsomal vesicles over time. Kinetic analysis was performed to determine the inhibition mode (competitive/non-competitive) with respect to ATP and Ca²⁺ [2] |
| Cell Assay |
- For rat hippocampal neuron experiment: Hippocampi were isolated from postnatal day 1-3 rat pups, and primary neuron cultures were established. After 14-21 days in culture, neurons were treated with Paxilline (1-10 μM) for 10-30 minutes. Whole-cell patch-clamp recordings were used to measure sEPSC frequency/amplitude and action potential amplitude. BK channel-mediated AHP was evaluated by recording the hyperpolarization amplitude after a train of action potentials; neuron viability was assessed by trypan blue staining to exclude cytotoxicity [3]
|
| Animal Protocol |
- For rat anticonvulsant experiment (MES and PTZ models): Adult male Sprague-Dawley rats (250-300 g) were randomly divided into control and Paxilline treatment groups. Paxilline was dissolved in dimethyl sulfoxide (DMSO) and diluted with saline (final DMSO concentration ≤ 5%) before administration. 1) MES model: Rats received i.p. injection of Paxilline (1, 3, 10 mg/kg) or vehicle 30 minutes before MES (50 mA, 0.2 seconds). Seizure severity was scored by the duration of tonic hindlimb extension, and seizure threshold was measured by increasing current until seizures occurred. 2) PTZ model: Rats received i.p. injection of Paxilline (3, 10, 30 mg/kg) or vehicle 30 minutes before PTZ (85 mg/kg, i.p.). Seizure onset time and severity (Racine scale) were recorded. Neurotoxicity was evaluated by the rotorod test (rats were placed on a rotating rod at 10 rpm for 60 seconds) 30 minutes after Paxilline injection [3]
|
| Toxicity/Toxicokinetics |
In rat anticonvulsant studies, Paxilline (at doses up to 30 mg/kg, intraperitoneal injection) did not cause neurotoxicity (no impairment in rotarod test) or death [3].
|
| References |
|
| Additional Infomation |
Paxilline is an indole diterpenoid alkaloid with the molecular formula C27H33NO4, isolated from Penicillium paxilli. It is a potent inhibitor of high-conductivity Ca2(+) and voltage-gated K(+) (BK) channels. It possesses multiple functions, including as a fungal toxin, a Penicillium metabolite, an anticonvulsant, an Aspergillus metabolite, a potassium channel blocker, a genotoxin, an anti-aging agent, and an EC 3.6.3.8 (Ca(2+) transporter ATPase) inhibitor. It is an organic heterohexacyclic compound, consisting of a tertiary alcohol, a terpenoid indole alkaloid, an enone, and a diterpenoid alkaloid. Paxilline has been reported in Aspergillus foveolatus, Claviceps paspali, and other organisms with relevant data.
- Paxilline is a toxic secondary metabolite isolated from Penicillium and Aspergillus fungi, and is primarily known as a selective BK channel antagonist[1],[3]. - Paxilline's channel-blocking mechanism for BK channels differs from other BK channel blockers (e.g., ibeloin), which primarily act on open channels[1]. - Paxilline is one of the few naturally occurring SERCA inhibitors that targets the ATP-binding domain of SERCA without interacting with the Ca²⁺-binding domain. [2] The anticonvulsant effect of Paxilline is attributed to its inhibition of neuronal BK channels, thereby reducing AHP and increasing the neuronal excitation threshold, thus inhibiting seizures[3]. |
| Molecular Formula |
C27H33NO4
|
|---|---|
| Molecular Weight |
435.5552
|
| Exact Mass |
435.24
|
| CAS # |
57186-25-1
|
| PubChem CID |
105008
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
648.8±55.0 °C at 760 mmHg
|
| Melting Point |
252ºC
|
| Flash Point |
346.2±31.5 °C
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
| Index of Refraction |
1.661
|
| LogP |
3.77
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
32
|
| Complexity |
868
|
| Defined Atom Stereocenter Count |
6
|
| SMILES |
C[C@]12CC[C@H]3C(=CC(=O)[C@H](O3)C(C)(C)O)[C@@]1(CC[C@@H]4[C@@]2(C5=C(C4)C6=CC=CC=C6N5)C)O
|
| InChi Key |
ACNHBCIZLNNLRS-UBGQALKQSA-N
|
| InChi Code |
InChI=1S/C27H33NO4/c1-24(2,30)23-20(29)14-18-21(32-23)10-11-25(3)26(4)15(9-12-27(18,25)31)13-17-16-7-5-6-8-19(16)28-22(17)26/h5-8,14-15,21,23,28,30-31H,9-13H2,1-4H3/t15-,21-,23-,25+,26+,27+/m0/s1
|
| Chemical Name |
(1S,2R,5S,7R,11S,14S)-11-hydroxy-7-(2-hydroxypropan-2-yl)-1,2-dimethyl-6-oxa-23-azahexacyclo[12.10.0.02,11.05,10.016,24.017,22]tetracosa-9,16(24),17,19,21-pentaen-8-one
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~229.59 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2959 mL | 11.4795 mL | 22.9589 mL | |
| 5 mM | 0.4592 mL | 2.2959 mL | 4.5918 mL | |
| 10 mM | 0.2296 mL | 1.1479 mL | 2.2959 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
