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 [6]. It has been included in an arm of the UK's RECOVERY trial. Click here to see al clochicine studies on ClinicalTrials.gov [8,10]. Colchicine is predicted to target inflammation and systemic clotting abnormalities that accompany COVID-19 [7,9-10]. 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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2D Structure
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Physico-chemical Properties
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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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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
References
1. Cifuentes M, Schilling B, Ravindra R, Winter J, Janik ME. (2006)
Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs.
Bioorg Med Chem Lett, 16 (10): 2761-4. [PMID:16504507]
2. Healy LD, McCarty OJT. (2019)
Contact system sends defensins to the rescue.
Blood, 133 (5): 385-386. [PMID:30705047]
3. Lucas X, Wohlwend D, Hügle M, Schmidtkunz K, Gerhardt S, Schüle R, Jung M, Einsle O, Günther S. (2013)
4-Acyl pyrroles: mimicking acetylated lysines in histone code reading.
Angew Chem Int Ed Engl, 52 (52): 14055-9. [PMID:24272870]
4. Machu TK. (1998)
Colchicine competitively antagonizes glycine receptors expressed in Xenopus oocytes.
Neuropharmacology, 37 (3): 391-6. [PMID:9681937]
5. Martínez GJ, Celermajer DS, Patel S. (2018)
The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation.
Atherosclerosis, 269: 262-271. [PMID:29352570]
6. Papadopoulos C, Patoulias D, Teperikidis E, Mouselimis D, Tsarouchas A, Toumpourleka M, Boulmpou A, Bakogiannis C, Doumas M, Vassilikos VP. (2020)
Colchicine as a Potential Therapeutic Agent Against Cardiovascular Complications of COVID-19: an Exploratory Review.
SN Compr Clin Med,: 1-11 [Epub ahead of print]. [PMID:32838182]
7. Reyes AZ, Hu KA, Teperman J, Wampler Muskardin TL, Tardif JC, Shah B, Pillinger MH. (2020)
Anti-inflammatory therapy for COVID-19 infection: the case for colchicine.
Ann Rheum Dis, [Epub ahead of print]. [PMID:33293273]
8. Sandhu T, Tieng A, Chilimuri S, Franchin G. (2020)
A Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection.
Can J Infect Dis Med Microbiol, 2020: 8865954. [PMID:33133323]
9. Schlesinger N, Firestein BL, Brunetti L. (2020)
Colchicine in COVID-19: an Old Drug, New Use.
Curr Pharmacol Rep,: 1-9 [Epub ahead of print]. [PMID:32837853]
10. Vrachatis DA, Giannopoulos GV, Giotaki SG, Raisakis K, Kossyvakis C, Iliodromitis KE, Reimers B, Tousoulis D, Cleman M, Stefanadis C et al.. (2021)
Impact of colchicine on mortality in patients with COVID-19: A meta-analysis.
Hellenic J Cardiol, [Epub ahead of print]. [PMID:33421583]