doxycycline   Click here for help

GtoPdb Ligand ID: 6464

Synonyms: BMY-28689 | Monodox® | Vibramycin®
Approved drug PDB Ligand Immunopharmacology Ligand Antimalarial Ligand
doxycycline is an approved drug (FDA (1967), UK (2000))
Compound class: Synthetic organic
Comment: Doxycycline is a tetracycline based antibiotic. It has been repurposed as a low-potency human metalloprotease inhibitor for periodontitis and is also used as an antimalarial therapy.
There are a number of salt forms in PubChem. The chemical structure we show here matches that of the consensus structure in PubChem, listed in the links table below. The DrugBank, ChEBI, ChEMBL and PDB entries for doxycycline show a different structure.
Doxycycline is one of the key access group antibacterials on the World Health Organization's Model List of Essential Medicines (link provided in the Classification table, under the Summary tab below).

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 6
Rotatable bonds 2
Topological polar surface area 181.62
Molecular weight 444.15
XLogP 0.39
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES CN(C1C(=O)C(=C(C2(C1C(O)C1C(C)c3cccc(c3C(=C1C2=O)O)O)O)O)C(=O)N)C
Isomeric SMILES CN([C@@H]1C(=O)C(=C([C@@]2([C@H]1[C@@H](O)[C@@H]1[C@@H](C)c3cccc(c3C(=C1C2=O)O)O)O)O)C(=O)N)C
InChI InChI=1S/C22H24N2O8/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29/h4-7,10,14-15,17,25-27,30,32H,1-3H3,(H2,23,31)/t7-,10+,14+,15-,17-,22-/m0/s1
InChI Key SGKRLCUYIXIAHR-AKNGSSGZSA-N
Bioactivity Comments
Doxycycline, like a number of other antibiotics including azithromycin and clindamycin, kills the malaria parasite in the lifecycle after treatment starts [2]. Consistent with this slow clinical action, the results provided in the table (whole organism assay data) below show that doxycycline is more potent in vitro against erythrocytic stage parasites when assessed two asexual life cycles after the initiation of treatment.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
MMP7 Primary target of this compound Hs Inhibitor Inhibition 4.1 pKd - 4
pKd 4.1 (Kd 7.3x10-5 M) [4]
MMP8 Hs Inhibitor Inhibition 4.6 pIC50 - 5
pIC50 4.6 (IC50 2.6x10-5 M) [5]
Whole organism assay data
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MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA PfW2 Ring formation assay (96 hours) - - 7.7 pIC50 - 2
pIC50 7.7 (IC50 2.11x10-8 M) FACS analysis following 96 hours in culture (third-generation rings) [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA Pf3D7 Ring formation assay (96 hours) - - 7.3 pIC50 - 2
pIC50 7.3 (IC50 4.53x10-8 M) FACS analysis following 96 hours in culture (third-generation rings) [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfW2 Ring formation assay (48 hours) - - 6.5 pIC50 - 2
pIC50 6.5 (IC50 3.3x10-7 M) FACS analysis following 48 hours in culture (second-generation rings) [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA Pf3D7 Ring formation assay (48 hours) - - 6.3 pIC50 - 2
pIC50 6.3 (IC50 5.32x10-7 M) FACS analysis following 48 hours in culture (second-generation rings) [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)