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

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 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
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 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
Classification Click here for help
Compound class Synthetic organic
Approved drug? Yes (FDA (2009))
IUPAC Name Click here for help
N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[d]heptalen-7-yl]acetamide
Synonyms Click here for help
Colcrys® | methoxylated analogue of XD1 | XD25
Database Links Click here for help
Specialist databases
GPCRdb Ligand colchicine
Reactome Drug Reactome logo R-ALL-9659877
Reactome Reaction Reactome logo R-HSA-9685830
Other databases
BindingDB Ligand 50014846
BitterDB Ligand 92
CAS Registry No. 64-86-8 (source: DrugBank)
ChEBI CHEBI:27882
ChEMBL Ligand CHEMBL107
DrugBank Ligand DB01394
DrugCentral Ligand 726
GtoPdb PubChem SID 135650118
PubChem CID 6167
RCSB PDB Ligand LOC
Search Google for chemical match using the InChIKey IAKHMKGGTNLKSZ-INIZCTEOSA-N
Search Google for chemicals with the same backbone IAKHMKGGTNLKSZ
UniChem Compound Search for chemical match using the InChIKey IAKHMKGGTNLKSZ-INIZCTEOSA-N
UniChem Connectivity Search for chemical match using the InChIKey IAKHMKGGTNLKSZ-INIZCTEOSA-N
Wikipedia Colchicine