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Drug Details

General Information of the Drug (ID: DR0683)
Name
Thioridazine
Synonyms
Aldazine; Mallorol; Malloryl; Meleril; Mellaril; Mellarit; Mellerets; Mellerette; Melleretten; Melleril; Melleryl; Metlaril; Novoridazine; Orsanil; Ridazine; Sonapax; Stalleril; Thioridazin; Thioridazinum; Thioxidazine; Tioridazin; Tioridazina; Thioridazine Hcl; Thioridazine Hcl Intensol; Thioridazine prolongatum; Thoridazine hydrochloride; Dl-Thioridazine; Mellaril (TN); Mellaril-S; Melleril (liquid); Novoridazine (TN); TP-21; Thioridazine, prolongatum; Thioridazinum [INN-Latin]; Thioril (TN); Tioridazina [INN-Spanish]; Mellaril-S (TN); Thioridazine (USP/INN); Thioridazine [USAN:INN:BAN]; Mellaril (*Hydrochloride*); (+-)-Thioridazine; 10-(2-(1-Methyl-2-piperidyl)ethyl)-2-(methylthio)phenothiazine; 10-[2-(1-methyl-2-piperidyl)ethyl]-2-methylsulfanyl-phenothiazine; 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-(methylsulfanyl)-10H-phenothiazine; 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-(methylthio)-10H-phenothiazine; 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfanylphenothiazine; 2-Methylmercapto-10-(2-(N-methyl-2-piperidyl)ethyl)phenothiazine; 3-Methylmercapto-N-(2'-(N-methyl-2-piperidyl)ethyl)phenothiazine
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Molecular Type
Small molecule
Disease Schizophrenia [ICD-11: 6A20] Approved [1]
Structure
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2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C21H26N2S2
PubChem CID
5452
Canonical SMILES
CN1CCCCC1CCN2C3=CC=CC=C3SC4=C2C=C(C=C4)SC
InChI
1S/C21H26N2S2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(24-2)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3
InChIKey
KLBQZWRITKRQQV-UHFFFAOYSA-N
CAS Number
CAS 50-52-2
ChEBI ID
CHEBI:9566
TTD Drug ID
D0U1OE
DrugBank ID
DB00679
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Up-regulation Expression GABPA  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Expression PSMA5  Molecule Info 
Pathway MAP
                    Biological
                    Regulation
Induction ROS generation
                    In-vitro Model AMC-HN-4 CVCL_5962 Tongue squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)
Thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis.
Target and Pathway
Target(s) Dopamine D2 receptor (D2R)  Molecule Info  [3]
KEGG Pathway Rap1 signaling pathway Click to Show/Hide
2 cAMP signaling pathway
3 Neuroactive ligand-receptor interaction
4 Gap junction
5 Dopaminergic synapse
6 Parkinson's disease
7 Cocaine addiction
8 Alcoholism
Panther Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway Click to Show/Hide
2 Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
3 Dopamine receptor mediated signaling pathway
4 Nicotine pharmacodynamics pathway
Reactome Dopamine receptors Click to Show/Hide
2 G alpha (i) signalling events
WikiPathways Hypothetical Network for Drug Addiction Click to Show/Hide
2 Monoamine GPCRs
3 GPCRs, Class A Rhodopsin-like
4 Genes and (Common) Pathways Underlying Drug Addiction
5 GPCR ligand binding
6 GPCR downstream signaling
7 Nicotine Activity on Dopaminergic Neurons
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 100).
Reference 2 NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin. Redox Biol. 2017 Oct;13:608-622.
Reference 3 Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4.
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Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China