| Size | Price | Stock | Qty |
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| Targets |
Human 5-HT1A receptor (serotonin receptor subtype 1A). AP521 is an agonist of the human 5-HT1A receptor with an IC50 of 94 nM. It acts mainly as a postsynaptic agonist of the 5-HT1A receptor, which plays a crucial role in the modulation of serotonergic neurotransmission. Activation of 5-HT1A receptors in the brain is associated with anxiolytic, antidepressant, and neuroprotective effects. The compound's benzothienopyridine structure contributes to its receptor binding affinity and selectivity.
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| ln Vitro |
AP521 is an agonist of human 5-HT1A receptor. The IC50 for 5-HT1A (rat), 5-HT1A (human), 5-HT1B (rat) and 5 are 135, 94, 254, 5530 and 418 correspondingly. , 422 and 198 nM for -HT1B (human), 5-HT1D (human), 5-HT5a (human) and 5-HT7 (rat) correspondingly. AP521 also lowers forskolin-induced cAMP buildup from 10 nM to 10 μM [1].
In vitro studies have shown that AP521 is a potent agonist of the human 5-HT1A receptor with an IC50 of 94 nM. The compound binds to the 5-HT1A receptor and activates downstream signaling pathways, modulating serotonergic neurotransmission. Its activity has been characterized in receptor binding and functional assays using cells expressing human 5-HT1A receptors. The compound's affinity and efficacy at other serotonin receptor subtypes and related targets have been evaluated to assess selectivity. |
| ln Vivo |
The amount of shocks received between doses of 0.5 and 10 mg/kg was considerably enhanced by AP521 [F(5,105)=4.46, P<0.01]. The freezing period may be considerably shortened by oral treatment of 3 and 10 mg/kg AP521 [F(3,60)=2.89, P<0.05]. The time to open the arm was nearly twice as long with AP521 as it was with the vehicle-treated group [F(3, 36)=4.21, P<0.05 for AP521]. It seems that AP521's anxiolytic-like effects are dose-related. After 0.5 to 1 hour of treatment, AP521 at 10 mg/kg dramatically raised extracellular 5-HT levels in the medial prefrontal cortex (mPFC). Extracellular 5-HT levels were somewhat raised by AP521 at 3 mg/kg, however this rise was not statistically significant [1].
In vivo studies have demonstrated the anxiolytic effects of AP521 in animal models. The effects of AP521 have been evaluated in three anxiety models and on serotonergic neural transmission in rats. The compound's anxiolytic activity is attributed to its agonism at 5-HT1A receptors, which modulates serotonin signaling in brain regions involved in anxiety regulation. AP521 has been investigated as a novel anxiolytic drug candidate with a potentially improved side-effect profile compared to benzodiazepines and other anxiolytics. |
| Enzyme Assay |
In vitro receptor binding assays for AP521 measure its affinity for the human 5-HT1A receptor. The assay uses membrane preparations from cells expressing recombinant human 5-HT1A receptors and a radiolabeled ligand such as [3H]-8-OH-DPAT or [3H]-WAY-100635. Varying concentrations of AP521 are incubated with membranes and radioligand. Non-specific binding is determined in the presence of excess unlabeled ligand. After incubation, bound and free radioligands are separated by filtration, and radioactivity is counted. IC50 and Ki values are calculated from competition curves using nonlinear regression analysis.
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| Cell Assay |
In vitro cell-based functional assays for AP521 measure 5-HT1A receptor activation. Cells expressing human 5-HT1A receptors are loaded with a fluorescent calcium indicator (e.g., Fluo-4) or co-transfected with a reporter gene (e.g., CRE-luciferase). Cells are stimulated with varying concentrations of AP521, and receptor activation is measured as an increase in intracellular calcium (for Gq-coupled assays) or cAMP inhibition (for Gi-coupled assays). EC50 values are calculated from dose-response curves. Antagonist activity can be assessed by co-incubation with a known 5-HT1A antagonist such as WAY-100635.
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| Animal Protocol |
In vivo animal studies for AP521 are conducted in rodent models of anxiety. Common models include the elevated plus maze, light/dark box, open field test, and social interaction test. Animals are administered AP521 orally or intraperitoneally at doses of 0.1-10 mg/kg, 30-60 minutes before testing. Anxiolytic-like behavior is assessed by increased time spent in open arms of the elevated plus maze or increased time in the light compartment of the light/dark box. Locomotor activity is monitored to rule out non-specific effects. Serotonergic neural transmission is assessed by microdialysis or by measuring serotonin levels in brain regions.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of AP521 are characteristic of small-molecule serotonin receptor agonists. With a molecular weight of 402.89, the compound is likely to have moderate oral bioavailability and blood-brain barrier penetration. The compound's benzothienopyridine structure contributes to its physicochemical properties. Standard pharmacokinetic parameters (Cmax, Tmax, AUC, half-life) can be determined in preclinical species following oral or intravenous administration. Storage at -20degC is recommended to maintain stability.
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| Toxicity/Toxicokinetics |
Toxicological data for AP521 are primarily derived from preclinical studies in animal models. As a research compound, comprehensive toxicity profiles are not extensively documented. The compound is intended for research purposes only and not for human therapeutic use. Standard safety precautions for handling chemical compounds apply. Acute and chronic toxicity studies have not been systematically reported for this compound.
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| References | |
| Additional Infomation |
AP521 is a research-grade benzothienopyridine derivative and 5-HT1A receptor agonist. It exhibits an IC50 of 94 nM for the human 5-HT1A receptor. The compound has been investigated as a novel anxiolytic drug candidate in preclinical models. Its molecular formula is C20H19ClN2O3S with a molecular weight of 402.89. AP521 acts as a postsynaptic agonist of the 5-HT1A receptor, modulating serotonergic neurotransmission. The compound is supplied for research use only and is not approved for clinical use. Not approved for clinical use.
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| Molecular Formula |
C20H19CLN2O3S
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| Molecular Weight |
402.894462823868
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| Exact Mass |
402.08
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| CAS # |
151227-08-6
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| PubChem CID |
9887401
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
533
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C([C@@H]1NCC2SC3C=CC=CC=3C=2C1)(=O)NCC1C=CC2OCOC=2C=1.Cl
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| InChi Key |
IPRJDKMLMDPMBH-XFULWGLBSA-N
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| InChi Code |
InChI=1S/C20H18N2O3S.ClH/c23-20(22-9-12-5-6-16-17(7-12)25-11-24-16)15-8-14-13-3-1-2-4-18(13)26-19(14)10-21-15;/h1-7,15,21H,8-11H2,(H,22,23);1H/t15-;/m1./s1
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| Chemical Name |
(3R)-N-(1,3-benzodioxol-5-ylmethyl)-1,2,3,4-tetrahydro-[1]benzothiolo[2,3-c]pyridine-3-carboxamide;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~62.05 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.21 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 25.0 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 (6.21 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4821 mL | 12.4103 mL | 24.8207 mL | |
| 5 mM | 0.4964 mL | 2.4821 mL | 4.9641 mL | |
| 10 mM | 0.2482 mL | 1.2410 mL | 2.4821 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.
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