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Showing metabocard for Ivermectin (HMDB0014740)
Record Information | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Version | 4.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Status | Expected but not Quantified | |||||||||||||||||||||||||||||||||||||||||||||||||||
Creation Date | 2012-09-06 15:16:50 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||
Update Date | 2017-12-07 02:47:10 UTC | |||||||||||||||||||||||||||||||||||||||||||||||||||
HMDB ID | HMDB0014740 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary Accession Numbers |
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Metabolite Identification | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Common Name | Ivermectin | |||||||||||||||||||||||||||||||||||||||||||||||||||
Description | Broad-spectrum anti-parasite medication, traditionally used against worms (except tapeworms), but more recently approved for the topical treatment of head lice infestations in patients 6 months of age and older. It is mainly used in humans in the treatment of onchocerciasis, but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis). | |||||||||||||||||||||||||||||||||||||||||||||||||||
Structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Synonyms |
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Chemical Formula | C95H146O28 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Average Molecular Weight | 1736.1589 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Monoisotopic Molecular Weight | 1735.000064088 | |||||||||||||||||||||||||||||||||||||||||||||||||||
IUPAC Name | (1'R,2R,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-6-(propan-2-yl)-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one; (1'R,2R,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-6-[(2R)-butan-2-yl]-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one | |||||||||||||||||||||||||||||||||||||||||||||||||||
Traditional Name | (1'R,2R,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-6-[(2R)-butan-2-yl]-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one; dihydroavermectin B1b | |||||||||||||||||||||||||||||||||||||||||||||||||||
CAS Registry Number | 70288-86-7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
SMILES | CO[C@H]1C[C@@H](O[C@@H](C)[C@@H]1O)O[C@H]1[C@H](C)O[C@H](C[C@@H]1OC)O[C@H]1[C@@H](C)\C=C\C=C2/CO[C@@H]3[C@H](O)C(C)=C[C@@H](C(=O)O[C@H]4C[C@@H](C\C=C1/C)O[C@@]1(CC[C@H](C)[C@@H](C(C)C)O1)C4)[C@]23O.CC[C@@H](C)[C@H]1O[C@@]2(CC[C@@H]1C)O[C@@H]1C\C=C(C)\[C@@H](O[C@@H]3O[C@@H](C)[C@H](O[C@@H]4O[C@@H](C)[C@H](O)[C@@H](OC)C4)[C@@H](OC)C3)[C@@H](C)\C=C\C=C3/CO[C@@H]4[C@H](O)C(C)=C[C@@H](C(=O)O[C@@H](C1)C2)[C@]34O | |||||||||||||||||||||||||||||||||||||||||||||||||||
InChI Identifier | InChI=1S/C48H74O14.C47H72O14/c1-11-25(2)43-28(5)17-18-47(62-43)23-34-20-33(61-47)16-15-27(4)42(26(3)13-12-14-32-24-55-45-40(49)29(6)19-35(46(51)58-34)48(32,45)52)59-39-22-37(54-10)44(31(8)57-39)60-38-21-36(53-9)41(50)30(7)56-38;1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-13-31-23-54-44-39(48)28(6)18-34(45(50)57-33)47(31,44)51)58-38-21-36(53-10)43(30(8)56-38)59-37-20-35(52-9)40(49)29(7)55-37/h12-15,19,25-26,28,30-31,33-45,49-50,52H,11,16-18,20-24H2,1-10H3;11-14,18,24-25,27,29-30,32-44,48-49,51H,15-17,19-23H2,1-10H3/b13-12+,27-15+,32-14+;12-11+,26-14+,31-13+/t25-,26+,28+,30+,31+,33-,34+,35+,36+,37+,38+,39+,40-,41+,42+,43-,44+,45-,47-,48-;25-,27-,29-,30-,32+,33-,34-,35-,36-,37-,38-,39+,40-,41+,42-,43-,44+,46+,47+/m10/s1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
InChI Key | SPBDXSGPUHCETR-CVSKBELMSA-N | |||||||||||||||||||||||||||||||||||||||||||||||||||
Chemical Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Description | This compound belongs to the class of organic compounds known as milbemycins. These are a group of macrolides with a structure containing a 16-membered lactone ring fused to a 1,7-dioxaspiroundecane ring system and to either a benzofuran (or hydrogenated derivative thereof). In some cases (e.g. Milbemycin E), the tetrahydrofuranyl ring is missing. Milbemycins can be o-glycosylated at C13 to form Avermectins. Milbemycins are produced by Streptomyces species. | |||||||||||||||||||||||||||||||||||||||||||||||||||
Kingdom | Organic compounds | |||||||||||||||||||||||||||||||||||||||||||||||||||
Super Class | Phenylpropanoids and polyketides | |||||||||||||||||||||||||||||||||||||||||||||||||||
Class | Macrolides and analogues | |||||||||||||||||||||||||||||||||||||||||||||||||||
Sub Class | Milbemycins | |||||||||||||||||||||||||||||||||||||||||||||||||||
Direct Parent | Milbemycins | |||||||||||||||||||||||||||||||||||||||||||||||||||
Alternative Parents | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Substituents |
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Molecular Framework | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
External Descriptors | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
Ontology | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Physiological effect | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Disposition | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Role | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Physical Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||
State | Solid | |||||||||||||||||||||||||||||||||||||||||||||||||||
Experimental Properties |
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Predicted Properties |
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Spectra | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Spectra |
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Biological Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Cellular Locations |
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Biospecimen Locations |
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Tissue Location | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
Pathways |
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Normal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Abnormal Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Predicted Concentrations | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Associated Disorders and Diseases | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Disease References | None | |||||||||||||||||||||||||||||||||||||||||||||||||||
Associated OMIM IDs | None | |||||||||||||||||||||||||||||||||||||||||||||||||||
External Links | ||||||||||||||||||||||||||||||||||||||||||||||||||||
DrugBank ID | DB00602 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Phenol Explorer Compound ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
FoodDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
KNApSAcK ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
Chemspider ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
KEGG Compound ID | C07970 | |||||||||||||||||||||||||||||||||||||||||||||||||||
BioCyc ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
BiGG ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
Wikipedia Link | Ivermectin | |||||||||||||||||||||||||||||||||||||||||||||||||||
METLIN ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
PubChem Compound | 46936176 | |||||||||||||||||||||||||||||||||||||||||||||||||||
PDB ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
ChEBI ID | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
References | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
Material Safety Data Sheet (MSDS) | Download (PDF) | |||||||||||||||||||||||||||||||||||||||||||||||||||
General References | Not Available |
Enzymes
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular weight:
- 57255.585
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in ion transport
- Specific function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
- Gene Name:
- GABRB3
- Uniprot ID:
- P28472
- Molecular weight:
- 54115.0
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
- Feng XP, Hayashi J, Beech RN, Prichard RK: Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. J Neurochem. 2002 Nov;83(4):870-8. [PubMed:12421359 ]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
- General function:
- Involved in ion transport
- Specific function:
- The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing)
- Gene Name:
- GLRA3
- Uniprot ID:
- O75311
- Molecular weight:
- 53799.8
References
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
- Yates DM, Wolstenholme AJ: An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria immitis. Int J Parasitol. 2004 Aug;34(9):1075-81. [PubMed:15313134 ]
- McCavera S, Rogers AT, Yates DM, Woods DJ, Wolstenholme AJ: An ivermectin-sensitive glutamate-gated chloride channel from the parasitic nematode Haemonchus contortus. Mol Pharmacol. 2009 Jun;75(6):1347-55. doi: 10.1124/mol.108.053363. Epub 2009 Mar 31. [PubMed:19336526 ]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Transporters
- General function:
- Involved in ATP binding
- Specific function:
- Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter
- Gene Name:
- ABCC2
- Uniprot ID:
- Q92887
- Molecular weight:
- 174205.6
References
- Lespine A, Dupuy J, Orlowski S, Nagy T, Glavinas H, Krajcsi P, Alvinerie M: Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3). Chem Biol Interact. 2006 Feb 25;159(3):169-79. Epub 2005 Dec 27. [PubMed:16384552 ]
- General function:
- Involved in ATP binding
- Specific function:
- Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency
- Gene Name:
- ABCC1
- Uniprot ID:
- P33527
- Molecular weight:
- 171589.5
References
- Lespine A, Dupuy J, Orlowski S, Nagy T, Glavinas H, Krajcsi P, Alvinerie M: Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3). Chem Biol Interact. 2006 Feb 25;159(3):169-79. Epub 2005 Dec 27. [PubMed:16384552 ]
- General function:
- Involved in ATP binding
- Specific function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular weight:
- 141477.3
References
- Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389 ]
- Pouliot JF, L'Heureux F, Liu Z, Prichard RK, Georges E: Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. Biochem Pharmacol. 1997 Jan 10;53(1):17-25. [PubMed:8960059 ]
- Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103 ]
- Schinkel AH, Wagenaar E, van Deemter L, Mol CA, Borst P: Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest. 1995 Oct;96(4):1698-705. [PubMed:7560060 ]
- Jani M, Makai I, Kis E, Szabo P, Nagy T, Krajcsi P, Lespine A: Ivermectin interacts with human ABCG2. J Pharm Sci. 2011 Jan;100(1):94-7. doi: 10.1002/jps.22262. Epub 2010 Jun 22. [PubMed:20574995 ]
- General function:
- Involved in ATP binding
- Specific function:
- Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
- Gene Name:
- ABCG2
- Uniprot ID:
- Q9UNQ0
- Molecular weight:
- 72313.5
References
- Jani M, Makai I, Kis E, Szabo P, Nagy T, Krajcsi P, Lespine A: Ivermectin interacts with human ABCG2. J Pharm Sci. 2011 Jan;100(1):94-7. doi: 10.1002/jps.22262. Epub 2010 Jun 22. [PubMed:20574995 ]