 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C15H25N3O5 |
| Molecular Weight | 327.38 |
| Exact Mass | 327.179 |
| Elemental Analysis | C, 55.03; H, 7.70; N, 12.84; O, 24.43 |
| CAS # | 2151842-64-5 |
| PubChem CID | 132155398 |
| Appearance | White to off-white solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 564.0±50.0 °C at 760 mmHg |
| Flash Point | 294.9±30.1 °C |
| Vapour Pressure | 0.0±3.5 mmHg at 25°C |
| Index of Refraction | 1.569 |
| LogP | 0.53 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 23 |
| Complexity | 530 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | C[C@H]([C@@H](C(=O)N)N1C[C@]2(C1=O)CCCN2C(=O)OC(C)(C)C)O |
| InChi Key | ABAPCYNTEPGBNJ-FTGAXOIBSA-N |
| InChi Code | InChI=1S/C15H25N3O5/c1-9(19)10(11(16)20)17-8-15(12(17)21)6-5-7-18(15)13(22)23-14(2,3)4/h9-10,19H,5-8H2,1-4H3,(H2,16,20)/t9-,10+,15+/m1/s1 |
| Chemical Name | tert-butyl (4S)-2-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]-3-oxo-2,5-diazaspiro[3.4]octane-5-carboxylate |
| Synonyms | Zelquistinel; 2151842-64-5; Zelquistinel [INN]; 387WYR6N95; UNII-387WYR6N95; AGN-241751; GATE251; GATE-251; |
| 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) |
Biological Activity
| Targets | Zelquistinel (AGN-241751) is a novel positive allosteric modulator of the NMDA receptor GluN2A subunit, binding to the amino-terminal domain (ATD) with an EC50 of 32 nM for enhancing glycine affinity. It exhibits >100-fold selectivity over GluN2B/C/D subunits. [1] |
| ln Vitro |
In Vitro: [1] In rat primary cortical neurons, Zelquistinel (0.1 μM) potentiated NMDA-induced currents by 142 ± 8% (p<0.001) in whole-cell patch-clamp recordings, confirming NMDA receptor modulation. Selectivity screening against 65 GPCRs, ion channels, and transporters showed no significant off-target activity (>10 μM IC50). [2] |
| ln Vivo |
In Vivo: [1] In the mouse forced swim test (FST), oral Zelquistinel (10 mg/kg) reduced immobility by 52% (p<0.001) at 2h post-dose, comparable to ketamine (10 mg/kg, 49% reduction). Chronic social defeat stress (CSDS) model: Daily dosing (3 mg/kg, 7 days) normalized sucrose preference (increased from 45±5% to 68±4%, p<0.01) and social interaction ratio (0.4±0.1 to 1.1±0.2, p<0.001). Synergy studies: Subeffective Zelquistinel (1 mg/kg) combined with subeffective ketamine (3 mg/kg) produced 47% FST immobility reduction (p<0.01). |
| Animal Protocol |
Animal Protocol: [1] Acute studies: Zelquistinel suspended in 10% Captisol® and administered orally at 1-30 mg/kg. Behavioral tests conducted 2h post-dose. Chronic studies: Daily oral dosing (1-10 mg/kg) for 7-14 days in CSDS mice. Tissue collection 24h post-final dose. |
| ADME/Pharmacokinetics |
ADME/Pharmacokinetics: [1] Oral bioavailability: 65% in mice, 78% in rats. Tmax: 0.5-1 h; plasma t½: 2.3 h (mice), 3.1 h (rats). Brain-to-plasma ratio: 0.9 at Cmax. |
| Toxicity/Toxicokinetics |
Toxicity/Toxicokinetics: [1] Plasma protein binding: 97%. No CYP450 inhibition (3A4/2D6) at 10 μM. LD50 >1000 mg/kg (mice, single dose). |
| References |
[1]. Burgdorf JS, et al., Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects. Int J Neuropsychopharmacol. 2022 Dec 12;25(12):979-991. [2]. Preparation of spiro-lactams as NMDA receptor modulators and uses thereof.WO2017201283A1. |
| Additional Infomation |
Additional Info: [1] Zelquistinel is an orally active spiro-lactam NMDA receptor modulator with rapid (2h) and sustained (24h) antidepressant-like effects. Phase 1 trials showed linear PK up to 200 mg. Synthetic route involves stereoselective [3+2] cycloaddition for spirocyclic core formation. Patent covers crystalline Form I (melting point 218-220°C). [2] |
Solubility Data
| Solubility (In Vitro) |
DMSO: 100 mg/mL (305.46 mM) H2O: 12.5 mg/mL (38.18 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.64 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 (7.64 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0546 mL | 15.2728 mL | 30.5455 mL | |
| 5 mM | 0.6109 mL | 3.0546 mL | 6.1091 mL | |
| 10 mM | 0.3055 mL | 1.5273 mL | 3.0546 mL |