| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
3C-like proteinase (3CLpro) of SARS-CoV and HCoV-229E. The drug is a serotonin receptor antagonist (5-HT receptor) in its original clinical application.
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| ln Vitro |
The binding affinities of sarnanserin/sarnanserin hydrochloride are observed for HCoV-229E 3CLpro and SARS-CoV 3CLpro. The KD value for human coronavirus 229E is 18.2 μM/36.6 μM (HCoV-229E) 3CLpro, while for SARS-related coronavirus (SARS-CoV) 3CLpro, it is 49.4 μM/78.0 μM[1]. Inhibiting the catalytic activity of SARS-CoV 3CLpro, the computed IC50 values of sarnanserin and sarnanserin hydrochloride are 4.92 μM and 5.05 μM, respectively. The comparable IC50 values of HCoV-229E 3CLpro are 4.68 μM and 5.68 μM. At doses up to 200 μM, none of these substances exhibit inhibitory effect against HRV-14 3Cpro [1].
Cinanserin HCl demonstrated significant and dose-dependent binding to bacterially expressed recombinant 3CLpro of both SARS-CoV and HCoV-229E, as determined by surface plasmon resonance (SPR) technology. The equilibrium dissociation constants (KD) were calculated as 78.0 µM for SARS-CoV 3CLpro and 36.6 µM for HCoV-229E 3CLpro. Cinanserin HCl inhibited the proteolytic activity of SARS-CoV 3CLpro and HCoV-229E 3CLpro in a fluorescence resonance energy transfer (FRET)-based enzyme assay using a fluorogenic peptide substrate. The 50% inhibitory concentration (IC50) values were 5.05 µM for SARS-CoV 3CLpro and 5.68 µM for HCoV-229E 3CLpro. Maximum inhibition of 70-90% was achieved at concentrations of 50-100 µM. Cinanserin HCl showed no detectable binding to or inhibitory activity against the related HRV-14 3Cpro at concentrations up to 200 µM, indicating specificity for coronavirus 3CLpro. |
| ln Vivo |
Cinnamonin (5 mg/kg; intravenous injection; 2 hours duration; male Wistar rats) treatment dramatically reduced systemic burn edema to shamburn levels. Administration of cinnamon significantly decreases leukocyte-endothelial interactions [2].
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| Enzyme Assay |
Surface Plasmon Resonance (SPR) Binding Assay: The binding affinity of Cinanserin HCl to viral proteinases was determined using a Biacore 3000 instrument. Recombinant SARS-CoV 3CLpro, HCoV-229E 3CLpro, and HRV-14 3Cpro were separately immobilized on a CM5 sensor chip via standard primary amine coupling. Various concentrations of Cinanserin HCl (ranging from 4.04 to 100 µM) were injected over the chip surface at a constant flow rate of 20 µL/min for 120 seconds, followed by a dissociation phase of over 150 seconds. Sensograms were processed, and equilibrium dissociation constants (KD) were calculated using Biacore evaluation software by fitting the data to a steady-state affinity model and a 1:1 Langmuir binding model.
FRET-based Enzymatic Activity Inhibition Assay: The inhibitory effect of Cinanserin HCl on the proteolytic activity of viral 3CLpro was measured using a fluorogenic peptide substrate (EDANS-Val-Asn-Ser-Thr-Leu-Gln-Ser-Gly-Leu-Arg-Lys-(Dabcyl)-Met). Purified enzymes (1 µM) were pre-incubated with varying concentrations of Cinanserin HCl (0 to 0.1 mM) for 2 hours at 4°C. The reaction was initiated by adding the substrate (10 µM) in assay buffer (100 mM NaCl, 20 mM phosphate buffer, pH 7.4) at 25°C. The increase in fluorescence emission at 490 nm (excitation at 340 nm) was monitored continuously for 60 minutes using a fluorescence spectrophotometer. The remaining enzymatic activity was calculated, and IC50 values were determined by fitting the inhibition data to a logistic derivative equation. |
| Cell Assay |
HCoV-229E Replicon Inhibition Assay: The antiviral activity of Cinanserin HCl against coronavirus replicase function was assessed using BHK-Rep-1 cells, a stable cell line containing an autonomously replicating HCoV-229E-based replicon RNA that mediates GFP expression. Cells were seeded in 96-well plates and treated with various concentrations of Cinanserin HCl for 3 days. GFP expression, a marker for viral replication, was analyzed by fluorescence microscopy and flow cytometry. The reduction in GFP-positive cells was calculated relative to untreated controls. Cytotoxicity was assessed in parallel on parental BHK-21 cells using the CellTitre 96 Aqueous One kit. At a concentration of 30 µg/mL (78 µM), GFP-expressing cells were reduced to 27% with no observable cytotoxicity.
SARS-CoV Infection Assay: Vero cells in 24-well plates were infected with SARS-CoV (Frankfurt isolate) at an MOI of 0.01 in a biosafety level 4 laboratory. After 1 hour, the inoculum was removed and replaced with fresh medium containing various concentrations of Cinanserin HCl. Two days post-infection, virus RNA in the supernatant was quantified by real-time RT-PCR, and infectious particles were quantified by immunofocus assay. Cell viability was measured using the MTT method. Cinanserin HCl reduced the SARS-CoV RNA concentration by over 2 log units and infectious particle titers correspondingly, with an IC50 of 13 µg/mL (34 µM) and an IC90 of 25 µg/mL (67 µM). No cytotoxicity was observed at the tested concentrations. HCoV-229E Infection Assay: MRC-5 cells in 24-well plates were infected with HCoV-229E at an MOI of 0.1. Cinanserin HCl was added post-infection. After 2 days, virus titers in the supernatant were determined by 50% tissue culture infectious dose (TCID50) assay, and virus RNA was quantified by dual-probe real-time RT-PCR. Cytotoxicity was assessed using the CellTitre 96 Aqueous One kit. Cinanserin HCl reduced the virus titer by over 4 log units, with an IC50 of 9.3 µg/mL (25 µM) based on titer reduction and 7.2 µg/mL (19 µM) based on RNA reduction. No toxicity was observed. |
| Animal Protocol |
Animal/Disease Models: Male Wistar rat (250 g) thermal injury [2]
Doses: 5 mg/kg Route of Administration: intravenous (iv) (iv)injection; lasted 2 hrs (hrs (hours)). Experimental Results: Whole body burn edema was Dramatically diminished to shamburn levels. |
| Toxicity/Toxicokinetics |
In dogs, the main side effect of Cinanserin was hepatotoxicity observed at repeated oral doses greater than 40 mg/kg per day. The lethal dose was 100 mg/kg upon intravenous infusion at a rate of 0.5 mg/kg per minute.
In rats, prolonged treatment at a high dosage level (120 mg/kg daily for 59 to 81 weeks) was associated with the development of malignant hepatoma. In small-scale human clinical trials from the 1960s, patients were treated for several weeks with oral doses of 600-800 mg/day (~10 mg/kg), and during short-term treatment, maximum daily doses of 1,200 mg (~20 mg/kg) were reached. No remarkable side effects were observed in these human trials. |
| References |
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| Additional Infomation |
Cinanserin hydrochloride is the hydrochloride salt of Cinanserin. It is an inhibitor of the SARS-CoV 3C-like protease, reducing viral replication in vitro. It has dual action as an antiviral, EC 3.4.22.69 (SARS coronavirus main protease) inhibitor, and anticoronavirus drug. It contains a Cinanserin (1+) domain. It is a serotonin antagonist with limited antihistamine, anticholinergic, and immunosuppressive activity.
Cinanserin (SQ 10,643) is a well-characterized serotonin receptor antagonist that underwent preliminary clinical testing in humans in the 1960s for conditions such as schizophrenia, mania, and carcinoid syndrome. This study repurposed it as a potential anti-SARS-CoV agent. The drug was identified as a candidate inhibitor of SARS-CoV 3CLpro through virtual screening of an 8,000-compound drug database (MDL-CMC) using a docking approach against a homology model of the enzyme, which was later confirmed with the X-ray crystal structure. Cinanserin HCl demonstrated strong inhibition of SARS-CoV and HCoV-229E replication in cell culture, reducing viral RNA and infectious particles by up to 4 log units at non-cytotoxic concentrations. Its antiviral effect is attributed primarily to inhibition of the viral 3CLpro, though additional mechanisms may contribute. Despite its promising in vitro antiviral activity, further clinical development of Cinanserin was historically suspended due to the finding of malignant hepatoma in long-term rat studies. However, the authors suggest it may serve as a lead compound for designing more active and less toxic 3CLpro inhibitors. |
| Molecular Formula |
C20H25CLN2OS
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| Molecular Weight |
376.94
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| Exact Mass |
376.138
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| CAS # |
54-84-2
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| Related CAS # |
1166-34-3 (Parent)
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| PubChem CID |
6433141
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| Appearance |
Light yellow to yellow solid powder
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| Boiling Point |
519.5ºC at 760mmHg
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| Flash Point |
268ºC
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| LogP |
5.257
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
25
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| Complexity |
391
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)CCCSC1=CC=CC=C1NC(=O)/C=C/C2=CC=CC=C2.Cl
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| InChi Key |
LXGJPDKYMJJWRB-IERUDJENSA-N
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| InChi Code |
InChI=1S/C20H24N2OS.ClH/c1-22(2)15-8-16-24-19-12-7-6-11-18(19)21-20(23)14-13-17-9-4-3-5-10-17;/h3-7,9-14H,8,15-16H2,1-2H3,(H,21,23);1H/b14-13+;
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| Chemical Name |
(E)-N-[2-[3-(dimethylamino)propylsulfanyl]phenyl]-3-phenylprop-2-enamide;hydrochloride
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| Synonyms |
Cinanserin HCl SQ-10643 Cinanserin 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, avoid exposure to moisture. |
| 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 : ~125 mg/mL (~331.62 mM)
H2O : ~100 mg/mL (~265.29 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.52 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 (5.52 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 (5.52 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 | 2.6529 mL | 13.2647 mL | 26.5294 mL | |
| 5 mM | 0.5306 mL | 2.6529 mL | 5.3059 mL | |
| 10 mM | 0.2653 mL | 1.3265 mL | 2.6529 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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