heparin   Click here for help

GtoPdb Ligand ID: 4214

Synonyms: HepFlush®
Approved drug
heparin is an approved drug (FDA (1939))
Compound class: Metabolite or derivative
Comment: Heparin is an endogenous secretory glycosaminoglycan (GAG) that is released predominantly from connective tissue mast cells. Isolated heparin is used clinically as an anti-coagulant. Structurally, heparins (generally known as unfractionated heparin) are a heterogeneous group of anionic, sulfated GAGs. Commercial preparations usually vary in size from 12-15 kDa, while a low molecular weight (fractionated) versions are also available. Database entries may specify the sodium salt forms.

SARS-CoV-2: There is strong experimental evidence which shows that heparin interacts directly with GAG-binding motifs on the Spike glycoprotein of SARS-CoV-2 [3], and that inhibiting this interaction can reduce SARS-CoV-2 infection of host cells [6,8]. These findings suggest that heparin may offer repurposing potential as a prophylactic COVID-19 therapeutic [2], in addition to its benefit as a treatment for COVID-19-related thrombotic complications.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 35
Hydrogen bond donors 14
Rotatable bonds 19
Topological polar surface area 588.61
Molecular weight 1039.04
XLogP -11.46
No. Lipinski's rules broken 3
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CC(=O)NC1C(OC2C(OC(C(C2O)O)OC2C(O)OC(C(C2CS(=O)(=O)O)OS(=O)(=O)O)OC2C(OC(C(C2O)OS(=O)(=O)O)O)C(=O)O)C(=O)O)OC(C(C1O)O)COS(=O)(=O)O
Isomeric SMILES CC(=O)N[C@H]1[C@@H](O[C@@H]2[C@H](O[C@H]([C@@H]([C@H]2O)O)O[C@@H]2[C@@H](O)O[C@@H]([C@@H]([C@H]2CS(=O)(=O)O)OS(=O)(=O)O)O[C@@H]2[C@@H](OC([C@@H]([C@H]2O)OS(=O)(=O)O)O)C(=O)O)C(=O)O)O[C@@H]([C@H]([C@@H]1O)O)COS(=O)(=O)O
InChI InChI=1S/C26H41NO34S4/c1-4(28)27-7-9(30)8(29)6(2-52-63(43,44)45)53-24(7)56-15-10(31)11(32)25(58-19(15)21(36)37)55-13-5(3-62(40,41)42)14(60-64(46,47)48)26(59-22(13)38)57-16-12(33)17(61-65(49,50)51)23(39)54-18(16)20(34)35/h5-19,22-26,29-33,38-39H,2-3H2,1H3,(H,27,28)(H,34,35)(H,36,37)(H,40,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)/t5-,6+,7+,8+,9+,10+,11+,12-,13-,14+,15-,16-,17+,18+,19-,22-,23?,24+,25+,26-/m0/s1
InChI Key ZFGMDIBRIDKWMY-PASTXAENSA-N
References
1. Gotti R, Parma B, Spelta F, Liverani L. (2013)
Affinity capillary electrophoresis in binding study of antithrombin to heparin from different sources.
Talanta, 105: 366-71. [PMID:23598032]
2. Gupta Y, Maciorowski D, Zak SE, Kulkarni CV, Herbert AS, Durvasula R, Fareed J, Dye JM, Kempaiah P. (2021)
Heparin: A simplistic repurposing to prevent SARS-CoV-2 transmission in light of its in-vitro nanomolar efficacy.
Int J Biol Macromol, 183: 203-212. [PMID:33915212]
3. Kim SY, Jin W, Sood A, Montgomery DW, Grant OC, Fuster MM, Fu L, Dordick JS, Woods RJ, Zhang F et al.. (2020)
Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions.
Antiviral Res, 181: 104873. [PMID:32653452]
4. Lindahl U, Li JP. (2020)
Heparin - An old drug with multiple potential targets in Covid-19 therapy.
J Thromb Haemost, 18 (9): 2422-2424. [PMID:32426897]
5. Poggiali E, Bastoni D, Ioannilli E, Vercelli A, Magnacavallo A. (2020)
Deep Vein Thrombosis and Pulmonary Embolism: Two Complications of COVID-19 Pneumonia?.
Eur J Case Rep Intern Med, 7 (5): 001646. [PMID:32399449]
6. Tandon R, Sharp JS, Zhang F, Pomin VH, Ashpole NM, Mitra D, McCandless MG, Jin W, Liu H, Sharma P et al.. (2021)
Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives.
J Virol, 95 (3). DOI: 10.1128/JVI.01987-20 [PMID:33173010]
7. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. (2020)
Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.
J Thromb Haemost, 18 (5): 1094-1099. [PMID:32220112]
8. Tree JA, Turnbull JE, Buttigieg KR, Elmore MJ, Coombes N, Hogwood J, Mycroft-West CJ, Lima MA, Skidmore MA, Karlsson R et al.. (2021)
Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations.
Br J Pharmacol, 178 (3): 626-635. [PMID:33125711]
9. UK Department of Health and Social Care. 
COVID-19 treatments could be fast-tracked through new national clinical trial initiative.
Accessed on 01/06/2020. Modified on 01/06/2020. gov.uk, https://www.gov.uk/government/news/covid-19-treatments-could-be-fast-tracked-through-new-national-clinical-trial-initiative