| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Zervimesine (CT-1812; CT1812; Elayta) is a novel, potent and orally bioavailable allosteric antagonist of the sigma-2 receptor complex (sigma-2/PGRMC1) that prevents and displaces binding of Aβ oligomers to neurons. By stopping a key initiating event in Alzheimer's disease, this first-in-class drug candidate mitigates downstream synaptotoxicity and restores cognitive function in aged transgenic mouse models of Alzheimer's disease. CT-1812 is being investigated by Cognition Therapeutics for Alzheimer's disease. CT1812 was well tolerated with single dose administration up to 1120 mg and with multiple dose administration up to 840 mg and 560 mg in healthy young and healthy elderly subjects, respectively. CT1812 is currently being studied in early phase 2 trials in patients with Alzheimer's disease.
| Targets |
Sigma-2 receptor complex：CT1812 acts as an allosteric antagonist with a Ki of 8.5 nM. [2]
|
|---|---|
| ln Vitro |
- Inhibition of Aβ oligomer binding：CT1812 (0.001–10 μM) dose-dependently prevents and displaces Aβ oligomer binding to neurons and glial cells in vitro, as measured by fluorescence-based assays and ELISA. This effect is specific to Aβ oligomers and not monomeric or fibrillar forms. [2]
- Synaptic protection：In primary cortical neuron cultures, CT1812 (4.8 μM, 48-hour treatment) increases the number of synaptic puncta and upregulates expression of synaptic proteins (e.g., synaptophysin) by 20–30%, as detected by immunofluorescence and Western blot. [2] |
| ln Vivo |
- Reduction of brain Aβ oligomers：In APP/PS1 transgenic mice, intravenous administration of CT1812 (0.3–3 mg/kg) reduces extracellular Aβ oligomer levels in the hippocampus and cortex by 30–50% (measured by ELISA), with no significant effect on total Aβ plaques. [2]
- Cognitive improvement in animal models：Oral CT1812 (10 mg/kg/day for 9 weeks) improves performance in the Morris water maze (decreased escape latency by 40%) and novel object recognition tests (increased discrimination index by 35%) in Thy1-huAPP mice, indicating enhanced memory function. [2] - CSF biomarker changes in humans：In a Phase 1 clinical trial, CT1812 (90–560 mg/day for 28 days) significantly reduces CSF levels of neurogranin (a synaptic damage marker) by 15–20% in healthy volunteers and early Alzheimer’s disease (AD) patients. [1] |
| Enzyme Assay |
Sigma-2 receptor binding assay：
1. Membrane preparations from cells expressing the sigma-2 receptor complex are incubated with CT1812 (0.01–1000 nM) and a radiolabeled ligand (e.g., [³H]-PB28) at 25°C for 60 minutes.
2. Bound and free ligands are separated by filtration, and radioactivity is measured. The Ki value is calculated using competition binding curves, confirming a Ki of 8.5 nM for CT1812. [2]
|
| Cell Assay |
- Aβ oligomer displacement assay：
1. Primary neurons or glial cells are pre-treated with CT1812 (0.1–10 μM) for 30 minutes, followed by addition of fluorescently labeled Aβ oligomers.
2. After 2-hour incubation, unbound Aβ oligomers are washed away, and retained fluorescence is measured. CT1812 reduces Aβ oligomer binding by 40–60% at 1 μM. [2]
- Synaptic protein expression assay： 1. Primary neuronal cultures are treated with CT1812 (4.8 μM) for 48 hours. 2. Cells are fixed and stained with antibodies against synaptophysin, and the number of synaptic puncta is quantified by microscopy. A 20–30% increase in synaptic density is observed. [2] |
| Animal Protocol |
- Transgenic mouse model of AD：
1. APP/PS1 or Thy1-huAPP mice (6–8 months old) are randomized to receive CT1812 or vehicle.
2. CT1812 is administered orally (10 mg/kg/day) or intravenously (0.3–3 mg/kg) for 9–10 weeks, dissolved in a mixture of DMSO and saline.
3. Cognitive function is assessed via behavioral tests (Morris water maze, novel object recognition), and brain tissues are analyzed for Aβ levels and synaptic proteins. [2]
|
| ADME/Pharmacokinetics |
- Oral absorption：In humans, CT1812 shows dose-proportional plasma concentrations after single oral doses (10–1120 mg), with a Tmax of 2–4 hours and half-life of 12–14 hours. [1]
- Brain penetration：In rodents, CT1812 achieves a brain-to-plasma concentration ratio of 1.9–3.3 after oral administration, indicating effective blood-brain barrier penetration. [2] - CSF distribution：In humans, CSF concentrations of CT1812 reach 20–50 nM at doses of 560 mg/day, correlating with plasma levels. [1] |
| Toxicity/Toxicokinetics |
- Safety in humans：In Phase 1 trials, CT1812 is well-tolerated at doses up to 1120 mg (single dose) and 840 mg (multiple doses). Adverse events include headache (15%), fatigue (10%), and nausea (8%), all mild to moderate. [1]
- No significant organ toxicity：Liver and kidney function tests (ALT, AST, creatinine) remain within normal ranges in treated subjects. [1] |
| References |
[1]. A phase 1 clinical trial of the sigma-2 receptor complex allosteric antagonist CT1812, a novel therapeutic candidate for Alzheimer's disease. Alzheimers Dement (N Y).2019. Jan 23;5:20-26.
[2]. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification. Alzheimers Dement. 2021 Aug;17(8):1365-1382. |
| Additional Infomation |
- Mechanism of action：CT1812 acts as an allosteric antagonist of the sigma-2 receptor complex, preventing Aβ oligomer binding to neurons, reducing synaptic damage, and preserving cognitive function in AD models. [2]
- Clinical development：CT1812 is being evaluated for the treatment of early Alzheimer’s disease, with Phase 1 data supporting its safety and ability to modulate synaptic biomarkers. [1][2] |
| Molecular Formula |
C24H33NO4S
|
|
|---|---|---|
| Molecular Weight |
431.588125944138
|
|
| Exact Mass |
431.213
|
|
| Elemental Analysis |
C, 66.79; H, 7.71; N, 3.25; O, 14.83; S, 7.43
|
|
| CAS # |
1802632-22-9
|
|
| Related CAS # |
1802632-22-9; 2315504-28-8 (funarate);
|
|
| PubChem CID |
118278088
|
|
| Appearance |
White to off-white solid powder
|
|
| LogP |
4.1
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
5
|
|
| Rotatable Bond Count |
7
|
|
| Heavy Atom Count |
30
|
|
| Complexity |
678
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
S(C)(C1C=CC2=C(C=1)CN(C2)C(C)(C)CCC1C=CC(=C(C=1)OC(C)(C)C)O)(=O)=O
|
|
| InChi Key |
ISQAPFMBJFZOLG-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C24H33NO4S/c1-23(2,3)29-22-13-17(7-10-21(22)26)11-12-24(4,5)25-15-18-8-9-20(30(6,27)28)14-19(18)16-25/h7-10,13-14,26H,11-12,15-16H2,1-6H3
|
|
| Chemical Name |
|
|
| Synonyms |
CT 1812; CT1812; 1802632-22-9; Sigma-2 receptor antagonist 1; 2-(tert-butoxy)-4-(3-methyl-3-(5-(methylsulfonyl)isoindolin-2-yl)butyl)phenol; 0661V34NTV; 4-[3-methyl-3-(5-methylsulfonyl-1,3-dihydroisoindol-2-yl)butyl]-2-[(2-methylpropan-2-yl)oxy]phenol; 2-tert-Butoxy-4-(3-(5-methanesulfonyl-1-1,3-dihydro-isoindol-1-yl)-3-methyl-butyl)-phenol; CT-1812
|
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.82 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 20.8 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: ≥ 2.08 mg/mL (4.82 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 20.8 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: ≥ 2.08 mg/mL (4.82 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 | 2.3170 mL | 11.5851 mL | 23.1701 mL | |
| 5 mM | 0.4634 mL | 2.3170 mL | 4.6340 mL | |
| 10 mM | 0.2317 mL | 1.1585 mL | 2.3170 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.
Plasma concentrations of CT1812 following a single oral dose (SAD) or after Q.D. dosing for 3 or 14days (MAD) in healthy young and elderly subjects.Alzheimers Dement (N Y).2019Jan 23;5:20-26. |
|---|
CT1812 concentrations in cerebrospinal fluid (CSF) increased in a dose-dependent manner.Alzheimers Dement (N Y).2019Jan 23;5:20-26. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
