LIGUSTRAZINE

ID: ALA303697

Max Phase: Preclinical

Molecular Formula: C8H12N2

Molecular Weight: 136.20

Molecule Type: Small molecule

Associated Items:

Representations

Synonyms (4): 2,3,5,6-Tetramethyl-Pyrazine | 2,3,5,6-Tetramethylpyrazine | Ligustrazine | Tetramethylpyrazine
Synonyms from Alternative Forms(4):

    Canonical SMILES:  Cc1nc(C)c(C)nc1C

    Standard InChI:  InChI=1S/C8H12N2/c1-5-6(2)10-8(4)7(3)9-5/h1-4H3

    Standard InChI Key:  FINHMKGKINIASC-UHFFFAOYSA-N

    Associated Targets(Human)

    HUVEC 11049 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    ECV-304 406 Activities

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    Homo sapiens 32628 Activities

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    Bile salt export pump 2311 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    K562 73714 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    A549 127892 Activities

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    HCT-116 91556 Activities

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    U-87 MG 3946 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Bel-7402 4577 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HT-29 80576 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HepG2 196354 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MCF7 126967 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    HeLa 62764 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SH-SY5Y 11521 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Thioredoxin reductase 269 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    A549/CDDP 63 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Histone deacetylase 6 20808 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    MDA-MB-231 73002 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Associated Targets(non-human)

    Plasma 649 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Rattus norvegicus 775804 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Thoracic aorta 838 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    PC-12 7051 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    SARS-CoV-2 38078 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Replicase polyprotein 1ab 11336 Activities

    Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

    Molecule Features

    Natural Product: YesOral: NoChemical Probe: NoParenteral: No
    Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
    Chirality: NoAvailability: NoProdrug: No

    Drug Indications

    MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

    Mechanisms of Action

    Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

    Properties

    Molecular Weight: 136.20Molecular Weight (Monoisotopic): 136.1000AlogP: 1.71#Rotatable Bonds: 0
    Polar Surface Area: 25.78Molecular Species: NEUTRALHBA: 2HBD: 0
    #RO5 Violations: 0HBA (Lipinski): 2HBD (Lipinski): 0#RO5 Violations (Lipinski): 0
    CX Acidic pKa: CX Basic pKa: 2.19CX LogP: 0.06CX LogD: 0.06
    Aromatic Rings: 1Heavy Atoms: 10QED Weighted: 0.54Np Likeness Score: -0.45

    References

    1. Liu X, Zhang R, Xu W, Li C, Zhao Q, Wang X..  (2003)  Synthesis of the novel liqustrazine derivatives and Their protective effect on injured vascular endothelial cell damaged by hydrogen peroxide.,  13  (13): [PMID:12798318] [10.1016/s0960-894x(03)00359-7]
    2. Wailzer B, Klocker J, Buchbauer G, Ecker G, Wolschann P..  (2001)  Prediction of the aroma quality and the threshold values of some pyrazines using artificial neural networks.,  44  (17): [PMID:11495591] [10.1021/jm001129m]
    3. Cheng XC, Liu XY, Xu WF, Guo XL, Ou Y..  (2007)  Design, synthesis, and biological activities of novel Ligustrazine derivatives.,  15  (10): [PMID:17383884] [10.1016/j.bmc.2007.03.033]
    4. Sun Y, Jiang J, Zhang Z, Yu P, Wang L, Xu C, Liu W, Wang Y..  (2008)  Antioxidative and thrombolytic TMP nitrone for treatment of ischemic stroke.,  16  (19): [PMID:18790647] [10.1016/j.bmc.2008.08.075]
    5. Cheng XC, Liu XY, Xu WF, Guo XL, Zhang N, Song YN..  (2009)  Ligustrazine derivatives. Part 3: Design, synthesis and evaluation of novel acylpiperazinyl derivatives as potential cerebrocardiac vascular agents.,  17  (8): [PMID:19329327] [10.1016/j.bmc.2009.03.012]
    6. Chen H, Li G, Zhan P, Liu X..  (2011)  Ligustrazine derivatives. Part 5: design, synthesis and biological evaluation of novel ligustrazinyloxy-cinnamic acid derivatives as potent cardiovascular agents.,  46  (11): [PMID:21993151] [10.1016/j.ejmech.2011.09.030]
    7. Sun Y, Zhang G, Zhang Z, Yu P, Zhong H, Du J, Wang Y..  (2012)  Novel multi-functional nitrones for treatment of ischemic stroke.,  20  (12): [PMID:22579617] [10.1016/j.bmc.2012.04.016]
    8. Chen H, Li G, Zhan P, Guo X, Ding Q, Wang S, Liu X.  (2013)  Design, synthesis and biological evaluation of novel ligustrazinylated derivatives as potent cardiovascular agents,  (5): [10.1039/C3MD20352B]
    9. PubChem BioAssay data set, 
    10. Chen H, Li G, Zhan P, Li H, Wang S, Liu X.  (2014)  Design, synthesis and biological evaluation of novel trimethylpyrazine-2-carbonyloxy-cinnamic acids as potent cardiovascular agents,  (6): [10.1039/C4MD00022F]
    11. Wang C, Wang P, Zeng W, Li W..  (2016)  Tetramethylpyrazine improves the recovery of spinal cord injury via Akt/Nrf2/HO-1 pathway.,  26  (4): [PMID:26786697] [10.1016/j.bmcl.2016.01.015]
    12. Warner DJ, Chen H, Cantin LD, Kenna JG, Stahl S, Walker CL, Noeske T..  (2012)  Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.,  40  (12): [PMID:22961681] [10.1124/dmd.112.047068]
    13. Zou Y, Zhao D, Yan C, Ji Y, Liu J, Xu J, Lai Y, Tian J, Zhang Y, Huang Z..  (2018)  Novel Ligustrazine-Based Analogs of Piperlongumine Potently Suppress Proliferation and Metastasis of Colorectal Cancer Cells in Vitro and in Vivo.,  61  (5): [PMID:29424539] [10.1021/acs.jmedchem.7b01096]
    14. Zou J, Gao P, Hao X, Xu H, Zhan P, Liu X..  (2018)  Recent progress in the structural modification and pharmacological activities of ligustrazine derivatives.,  147  [PMID:29432947] [10.1016/j.ejmech.2018.01.097]
    15. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]
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    17. Zhang WX, Wang H, Cui HR, Guo WB, Zhou F, Cai DS, Xu B, Jia XH, Huang XM, Yang YQ, Chen HS, Qi JC, Wang PL, Lei HM..  (2019)  Design, synthesis and biological evaluation of cinnamic acid derivatives with synergetic neuroprotection and angiogenesis effect.,  183  [PMID:31541868] [10.1016/j.ejmech.2019.111695]
    18. Ai Y, Zhu B, Ren C, Kang F, Li J, Huang Z, Lai Y, Peng S, Ding K, Tian J, Zhang Y..  (2016)  Discovery of New Monocarbonyl Ligustrazine-Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer.,  59  (5): [PMID:26891099] [10.1021/acs.jmedchem.5b01203]
    19. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
    20. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
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