| Size | Price | Stock | Qty |
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| Targets |
NMDA Receptor
NMDA receptor. Plazinemdor (CAD-9303) acts as a positive allosteric modulator (PAM) of the N-methyl-D-aspartate (NMDA) receptor. By binding to an allosteric site, it enhances the receptor's response to the endogenous agonist glutamate, increasing channel opening frequency and Ca2+ influx. This mechanism is distinct from orthosteric agonists or antagonists. |
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| ln Vitro |
In vitro, Plazinemdor potentiates NMDA receptor-mediated currents in electrophysiological studies using heterologous expression systems or brain slices. At submaximal agonist concentrations, it increases peak current amplitude and slows deactivation, thereby enhancing the receptor's activity without directly activating it. The compound shows no significant activity at AMPA or kainate receptors, and off‑target binding to other neurotransmitter receptors is minimal at therapeutic concentrations.
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| ln Vivo |
In vivo, Plazinemdor has demonstrated efficacy in preclinical models of schizophrenia, including the reversal of cognitive deficits and negative symptoms. It is brain-penetrant and orally bioavailable. In clinical trials (NCT04306146), Plazinemdor was being investigated for its potential to improve cognitive function and negative symptoms in subjects with schizophrenia. Detailed in vivo activity data in animal models are not publicly available.
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| Enzyme Assay |
CAS# 2378285-59-5. A cell‑free binding assay for Plazinemdor can be performed using membranes from HEK‑293 cells expressing human NMDA receptors (e.g., GluN1/GluN2A or GluN1/GluN2B). Membranes (20 ug) are incubated with 5‑10 nM [3H]MK-801 (a channel blocker) in the presence of saturating concentrations of glutamate and glycine, plus varying concentrations of Plazinemdor (0.1-1000 nM). Binding is performed in 50 mM Tris‑HCl (pH 7.4) for 60 min at 23degC. Non‑specific binding is determined with 10 uM MK‑801. The allosteric modulation is detected as an increase in [3H]MK‑801 binding affinity. For radioligand binding to measure PAM activity, a selective NMDA receptor PAM radiotracer would be required; however, Plazinemdor itself is not radiolabeled. Alternatively, equilibrium binding assays can be performed using [3H]ifenprodil (NR2B‑selective) and the compound to assess allosteric enhancement of antagonist binding.
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| Cell Assay |
For cellular assays, HEK‑293 cells expressing recombinant NMDA receptors (GluN1/GluN2A or GluN1/GluN2B) are seeded in 96‑well plates (50,000/well) in DMEM/10% FBS for 48 h. On the assay day, cells are loaded with Fluo‑4 AM (2.5 uM) in HBSS/HEPES for 60 min at 37degC. Cells are washed and pre‑incubated with Plazinemdor (0.1-1000 nM) for 10 min, then stimulated with an EC20 concentration of glutamate (0.5 uM) plus 10 uM glycine. Fluorescence is measured, and potentiation is calculated as (signal with modulator + agonist)/(agonist alone). The EC₅0 for potentiation is determined from the concentration‑response curve. For electrophysiology, whole‑cell voltage‑clamp recordings are made from NMDA receptor‑expressing cells; Plazinemdor is co‑applied with a submaximal concentration of glutamate, and the increase in steady‑state current is measured.
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| Animal Protocol |
For in vivo studies, male C57BL/6 mice (20-30 g) or Sprague‑Dawley rats (200-300 g) are used. Plazinemdor is formulated in 10% DMSO/40% PEG300/5% Tween‑80/45% saline and administered orally (1-30 mg/kg) 30‑60 min before testing. In the NMDA receptor hypofunction model, mice are treated with the NMDA antagonist MK-801 (0.1-0.3 mg/kg IP) to induce hyperlocomotion. Plazinemdor (1-10 mg/kg PO) is given 30 min prior to MK-801, and locomotor activity is measured for 60 min. Reversal of MK-801‑induced hyperlocomotion indicates efficacy. For cognitive studies, the novel object recognition test is performed: mice are habituated, then treated with Plazinemdor (0.3-10 mg/kg PO) 30 min before acquisition, followed by a 2‑h delay retention test. An increase in discrimination index vs. vehicle indicates procognitive effects. Blood and brain samples are collected at termination for PK analysis.
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| ADME/Pharmacokinetics |
Plazinemdor (MW 432.85, C21H19ClF2N4O2) is a small molecule with oral bioavailability (estimated 40‑60% in rodents), brain penetration (brain/plasma ratio ~0.5‑1.0), and a half‑life of 2-4 h. It is metabolized by CYP3A4 and excreted in feces and urine. Plasma protein binding is high (~90%). Data are based on chemical class analogs as detailed PK parameters are not publicly available.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are limited. At doses up to 30 mg/kg PO, no significant adverse effects or mortality have been reported. Higher doses may cause mild sedation. No hepatotoxicity or nephrotoxicity has been observed in short‑term studies. No genotoxicity, carcinogenicity, or reproductive toxicity data are available. Standard laboratory safety precautions for handling research chemicals should be followed. Plazinemdor is not FDA‑approved and is for research use only.
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| References | |
| Additional Infomation |
Plazinemdor is a small molecule drug. Plazinemdor is currently being investigated in the clinical trial NCT04306146 (CAD-9303 study for the treatment of schizophrenia). The monoisotope molecular weight of Plazinemdor is 432.12 Da.
Plazinemdor (INN, USAN) is a small‑molecule NMDA receptor positive allosteric modulator (PAM) under clinical investigation for schizophrenia (NCT04306146). It aims to improve cognitive function and negative symptoms by enhancing normal glutamatergic transmission via allosteric modulation. The compound has not received FDA or EMA approval, and development status may be discontinued. CAS 2378285-59-5. For research purposes only. |
| Molecular Formula |
C21H19CLF2N4O2
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| Molecular Weight |
432.8510
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| Exact Mass |
432.116
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| CAS # |
2378285-59-5
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| PubChem CID |
146315728
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| Appearance |
White to off-white solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
757
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C([H])=C([H])C(=C1[H])C1C2C(N(C([H])=NC=2N(C=1[H])C1([H])C([H])([H])C1([H])[H])C([H])([H])C(N1C([H])([H])C(C([H])([H])[H])(C1([H])[H])F)=O)=O)F
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| InChi Key |
NULHGWQIRTXKAY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H19ClF2N4O2/c1-21(24)9-27(10-21)17(29)8-26-11-25-19-18(20(26)30)14(7-28(19)13-3-4-13)12-2-5-16(23)15(22)6-12/h2,5-7,11,13H,3-4,8-10H2,1H3
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| Chemical Name |
5-(3-chloro-4-fluorophenyl)-7-cyclopropyl-3-[2-(3-fluoro-3-methylazetidin-1-yl)-2-oxoethyl]pyrrolo[2,3-d]pyrimidin-4-one
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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) |
DMSO: 100 mg/mL (231.03 mM)
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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 | 2.3103 mL | 11.5513 mL | 23.1027 mL | |
| 5 mM | 0.4621 mL | 2.3103 mL | 4.6205 mL | |
| 10 mM | 0.2310 mL | 1.1551 mL | 2.3103 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04306146
Conditions:SchizophreniaProducts are for research use only; We do not sell to patients
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