| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
5-HT2 receptors (serotonin 2 receptors)
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|---|---|
| ln Vitro |
Zalsupindole (DLX-001; AAZ-A 154) is a first-in-class, non-hallucinogenic psychoplastogen—a small molecule that promotes neuronal growth—developed by Delix Therapeutics for the treatment of major depressive disorder and other central nervous system conditions. Structurally, it is a synthetic tryptamine derivative with the molecular formula C14H20N2O . Unlike classical psychedelics that also act on the 5-HT2A receptor but cause hallucinations, zalsupindole is designed as a biased agonist. It aims to separate the therapeutic benefits of rapid neuroplasticity from the psychotomimetic side effects, thereby offering a safer and more scalable treatment option.
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| ln Vivo |
In rodent models, zalsupindole produces rapid and sustained antidepressant-like effects following a single dose, as evidenced by efficacy in the forced swim test and VMAT2-deficient mouse models. Its effects on structural neuroplasticity are comparable to or greater than those of ketamine, psilocybin, and DMT. Critically, despite its 5-HT2A activity, zalsupindole does not induce the head-twitch response (HTR) in rodents, which is the primary behavioral proxy for hallucinations in humans, confirming its non-hallucinogenic profile.
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| Enzyme Assay |
While a specific step-by-step protocol was not detailed in the summaries, the standard methodology for characterizing zalsupindole involves radioligand binding assays using membranes from cells expressing human recombinant serotonin receptors (e.g., 5-HT2A, 5-HT2B, 5-HT2C). In these cell-free systems, increasing concentrations of zalsupindole compete with a high-affinity radioligand (such as [3H]-ketanserin for 5-HT2A) to determine its binding affinity (Ki value). Functional bias is subsequently assessed using non-radioactive methods like IP-1 accumulation or β-arrestin recruitment assays to differentiate between Gq and β-arrestin signaling pathways.
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| Cell Assay |
Cellular activity is typically assessed using primary rodent cortical neurons or human induced pluripotent stem cell (iPSC)-derived neurons. The protocol involves treating cultured neurons with varying concentrations of zalsupindole (or control compounds like ketamine or psilocybin) for a defined period (often 24-72 hours). Neuroplasticity is quantified through high-content imaging to measure neurite length, branching, and number of synaptic puncta (e.g., PSD-95 staining). The dependency on the 5-HT2A receptor is validated by pre-incubating cells with ketanserin before compound addition.
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| Animal Protocol |
Cellular activity is typically assessed using primary rodent cortical neurons or human induced pluripotent stem cell (iPSC)-derived neurons. The protocol involves treating cultured neurons with varying concentrations of zalsupindole (or control compounds like ketamine or psilocybin) for a defined period (often 24-72 hours). Neuroplasticity is quantified through high-content imaging to measure neurite length, branching, and number of synaptic puncta (e.g., PSD-95 staining). The dependency on the 5-HT2A receptor is validated by pre-incubating cells with ketanserin before compound addition.
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| ADME/Pharmacokinetics |
In rat studies, zalsupindole demonstrates rapid brain penetration after systemic administration, suggesting good blood-brain barrier permeability. Data from Phase 1 human clinical trials indicate that the drug exhibits linear pharmacokinetics with dose-proportional absorption across a wide range (2 mg to 360 mg). It shows high central nervous system (CNS) penetration, and its absorption profile supports oral dosing. Electroencephalogram (EEG) biomarkers in humans showed dose-dependent increases in power spectra associated with synaptic potentiation, confirming target engagement in the brain.
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| Toxicity/Toxicokinetics |
Preclinical safety assessments highlight a favorable safety profile. Zalsupindole lacks measurable agonism at the 5-HT2B receptor, mitigating the risk of drug-induced valvular heart disease associated with some serotonergic drugs. In Phase 1 clinical trials, oral zalsupindole was reported to be well-tolerated across a dose range of 2–360 mg. There were no reports of psychotomimetic effects (hallucinations or dissociation), traditional drug-related adverse events of psychedelics, or significant toxicity signals.
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| References |
| Molecular Formula |
C14H21CLN2O
|
|---|---|
| Molecular Weight |
268.78
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| CAS # |
2930845-89-7
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| Related CAS # |
2481740-94-5; 2930845-96-6 (HBr); 2930845-92-2 (benzoate); 2930845-89-7 (HCl); 2481740-95-6 (fumarate); 2930845-94-4; 2930846-03-8 (mesylate); 2481741-75-5 (S-isomer free base)
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
C[C@H](CN1C=CC2=C1C=CC(=C2)OC)N(C)C.Cl
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| Synonyms |
AAZ-A-154 hydrochloride; DTXSID901336869; AAZA154 HCl; AAZ-A-154 HCl; AAZA-154 HCl; RefChem:1075133; DTXCID001767164; AAZ-A 154 HCl; AAZ-A154 HCl; AAZA 154 HCl; DLX-001 HCl; DLX 001 HCl; DLX001 HCl; 2481740-94-5;
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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 |
| 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) |
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
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|---|---|
| Solubility (In Vivo) |
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 Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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)] Oral Formulations
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 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7205 mL | 18.6026 mL | 37.2051 mL | |
| 5 mM | 0.7441 mL | 3.7205 mL | 7.4410 mL | |
| 10 mM | 0.3721 mL | 1.8603 mL | 3.7205 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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