colchicine   Click here for help

GtoPdb Ligand ID: 2367

Synonyms: Colcrys® | methoxylated analogue of XD1 | XD25
Approved drug PDB Ligand Immunopharmacology Ligand
colchicine is an approved drug (FDA (2009))
Compound class: Synthetic organic
Comment: Colchicine is a microtubule inhibitor. It is a methoxylated analogue of XD1 (colchicein).

SARS-CoV-2 and COVID-19: There are a number of clinical trials looking at the efficacy of colchicine as a therapy to help treat, and/or prevent the development of, severe symptoms in COVID-19 patients [7]. It has been included in an arm of the UK's RECOVERY trial. Click here to see al clochicine studies on ClinicalTrials.gov [9,11]. Colchicine is predicted to target inflammation and systemic clotting abnormalities that accompany COVID-19 [8,10-11]. This repositioning of colchicine is based both on the drug's established anti-inflammatory action, on its ability to inhibit NLRP3 inflammasome activation, and on experimental evidence that colchicine-induced neutrophil depletion inhibits the release of the endogenous antimicrobial peptide α-defensin-1 (DEFα-1; DEFA1) and reduces thrombus formation in experimental models [2]. Background: contact factors (such as kallikrein and FXIIa) connect inflammation to the activation of coagulation, via promoting the production of DEFα-1 by activated neutrophils. DEFα-1 has pro-thrombotic activity, acting to both stabilise fibrin and thrombus formation and impeding clot resolution by reducing fibrinolysis [2].
In early 2021, preliminary data from the Phase 3 ColCORONA study (NCT04322682) provided some evidence that colchicine reduced hospitalisation (by 25%), progression to mechanical ventilation (by 50%) or death (by 44%) in >4100 confirmed COVID-19 patients, compared to placebo. The drug was given in an outpatient setting. A medRxiv preprint providing more details from the ColCORONA study was posted on 27th January 2021 (DOI: 10.1101/2021.01.26.21250494v1) prior to the peer review process being completed. In contrast a preprint of results from the colchicine arm of the RECOVERY trial (11340 hospitalised COVID-19 patients) reported no clinical benefit compared to standard care by any of the primary or secondary outcome measures (Horby et al., 2021; medRxiv https://doi.org/10.1101/2021.05.18.21257267).
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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

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View more information in the IUPHAR Pharmacology Education Project: colchicine

colchicine is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 3
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 83.09
Molecular weight 399.17
XLogP 2.96
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1c(OC)cc2c(c1OC)c1ccc(c(=O)cc1C(CC2)NC(=O)C)OC
Isomeric SMILES COc1c(OC)cc2c(c1OC)c1ccc(c(=O)cc1[C@H](CC2)NC(=O)C)OC
InChI InChI=1S/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1
InChI Key IAKHMKGGTNLKSZ-INIZCTEOSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Colchicine is an oral drug that is primarily used to treat gout. It can also be used to treat autoinflammatory conditions such as Behcet's syndrome. Colchicine was approved for use in combination with probenecid as early as 1961. Full US FDA approval was only granted for the single ingredient drug in 2009, although it had been marketed prior to this date without formal approval.
In June 2023, the FDA approved the use of colchicine as an anti-inflammatory atheroprotective cardiovascular treatment. In this setting colchicine is expected to reduce the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in patients with established atherosclerotic disease or at high risk of developing cardiovascular disease.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
CHEMBL lists tubulin as the target of colchicine inhibition, and data suggests this may play a part in its effectiveness against gout (killing inflammatory leukocytes by disabling microtubule formation). The major antigout mechanism of colchicine is believed to be its ability to inhibit urate crystal deposition and the subsequent inflammatory response that initiates and sustains acute gout episodes.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04472611 Colchicine/Statins for the Prevention of COVID-19 Complications (COLSTAT) Trial Phase 3 Interventional Yale University
NCT04416334 PREEMPTIVE THERAPY WITH COLCHICINE IN PATIENTS OLDER THAN 70 YEARS WITH HIGH RISK OF SEVERE PNEUMONIAE DUE TO CORONAVIRUS Phase 3 Interventional Instituto de Investigación Marqués de Valdecilla
NCT04360980 The Effects of Standard Protocol With or Without Colchicine in Covid-19 Infection Phase 2 Interventional Shahid Beheshti University of Medical Sciences
NCT04322682 Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) Phase 3 Interventional Montreal Heart Institute
NCT04328480 The ECLA PHRI COLCOVID Trial. Effects of Colchicine on Moderate/High-risk Hospitalized COVID-19 Patients. Phase 3 Interventional Estudios Clínicos Latino América
NCT04326790 The GReek Study in the Effects of Colchicine in Covid-19 cOmplications Prevention Phase 2 Interventional National and Kapodistrian University of Athens
NCT04322565 Colchicine Counteracting Inflammation in COVID-19 Pneumonia Phase 2 Interventional Azienda Ospedaliero-Universitaria di Parma