Natural Product (NP) Details

General Information of the NP (ID: NP8547)
Name
Roxithromycin
Synonyms
roxithromycin; Rulide; Roxithromycine; Roxithromycinum; Roxitromicina; 80214-83-1; RU 965; RU 28965; UNII-21KOF230FA; RU-965; Rulid; CHEBI:48935; 21KOF230FA; RU-28965; 9-(O-((2-Methoxyethoxy)methyl)oxime)erythromycin; (9E)-erythromycin 9-(O-((2-methoxyethoxy)methyl)oxime); (E)-roxithromycin; Roxithromycine [French]; Roxithromycinum [Latin]; Roxitromicina [Spanish]; Rulide (TN); 9-[O-[(2-Methoxyethoxy)methyl]oxime]erythromycin; SR-05000001850; CHEBI:48844; CCRIS 3461; Roxithromycin,(S); (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10; (3R,4S,5S,6R,7R,9R,11S,12R,13S,14R,E)-6-(((2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-14-ethyl-7,12,13-trihydroxy-4-(((2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl)oxy)-10-(((2-methoxyethoxy)methoxy)imino)-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one; Erythromycin 9-(O-((2-methoxyethoxy)methyl)oxime); Roxithromycin [USAN:INN:BAN:JAN]; RC2952; BRN 4286925; Spectrum5_001058; SCHEMBL65985; BSPBio_002717; SPECTRUM1503276; 9-[O-(2-methoxyethoxymethyl)-oxime] of erythromycin; Erythromycin, 9-(O-((2-methoxyethoxy)methyl)oxime); CHEMBL1214185; HMS501D04; Erythromycin, 9-(O-((2-methoxyethoxy)methyl)oxime), (9E)-; HMS1922O19; HMS2093C11; HMS3714L09; Pharmakon1600-01503276; Roxithromycin (JP17/USAN/INN); HY-B0435; BDBM50248154; CCG-39329; NSC758443; ZINC96061888; AKOS015969730; DB00778; NSC 758443; NSC-758443; IDI1_000382; NCGC00178510-01; SBI-0051809.P002; Roxithromycin 100 microg/mL in Acetonitrile; C13173; D01710; AB00052342_02; SR-05000001850-1; SR-05000001850-2; BRD-K38684403-001-03-9; BRD-K38684403-001-05-4; Q27895851; 9-[O-[(2-Methoxyethoxy)methyl]oxime]erythromycin, (9E)-; (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-4-(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyloxy)-14-ethyl-7,12,13-trihydroxy-10-{[(2-methoxyethoxy)methoxy]imino}-6-[3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyloxy]-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one; (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyl-tetrahydropyran-2-yl]oxy-10-(2-methoxyethoxymethoxyimino)-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one; (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-10-{[(2-methoxyethoxy)m; (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-10-{[(2-methoxyethoxy)methoxy]imino}-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one; (3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione 10-{O-[(2-methoxyethoxy)methyl]oxime} (non-preferred name); (3R,4S,5S,6R,7R,9R,11S,12R,13S,14R)-4-(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyloxy)-14-ethyl-7,12,13-trihydroxy-10-{[(2-methoxyethoxy)methoxy]imino}-6-[3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyloxy]-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one; (3R,4S,5S,6R,7R,9R,11S,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-3,5,7,9,11,13-hexamethyl-10-(2,4,7-trioxa-1-azaoctan-1-ylidene)-1-oxacyclotetradecan-2-one; (3R,4S,5S,6R,7R,9R,11S,12R,13S,14R,E)-6-(((2S,3R,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-14-ethyl-7,12,13-trihydroxy-4-(((2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl)oxy)-10-(((2-methoxyethoxy)methoxy)imino)-3,5,7,9,11,13-hexamethyloxacyclotetradecan-2-one
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Species Origin Escherichia coli ...     Click to Show/Hide
Escherichia coli
SuperKingdom: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli
Disease Bacterial infection [ICD-11: 1A00-1C4Z] Withdrawn from market [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.821
 
MDCK Permeability
 -5.218
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 -0.002
 
PPB
 48%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 +++
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 +++
CYP2B6 inhibitor
 +++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - -
HLM Stability
 ++
 
Excretion
CLplasma
 4.644
 
T1/2
 4.397
Toxicity
DILI
 ++
 
Rat Oral Acute Toxicity
 - - -
 
FDAMDD
 - - -
 
Respiratory
 - - -
 
Human Hepatotoxicity
 -
 
Ototoxicity
 +++
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 -
 
Hematotoxicity
 -
 
Genotoxicity
 - - -
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C41H76N2O15
PubChem CID
6915744
Canonical SMILES
CCC1C(C(C(C(=NOCOCCOC)C(CC(C(C(C(C(C(=O)O1)C)OC2CC(C(C(O2)C)O)(C)OC)C)OC3C(C(CC(O3)C)N(C)C)O)(C)O)C)C)O)(C)O
InChI
1S/C41H76N2O15/c1-15-29-41(10,49)34(45)24(4)31(42-53-21-52-17-16-50-13)22(2)19-39(8,48)36(58-38-32(44)28(43(11)12)18-23(3)54-38)25(5)33(26(6)37(47)56-29)57-30-20-40(9,51-14)35(46)27(7)55-30/h22-30,32-36,38,44-46,48-49H,15-21H2,1-14H3/b42-31+/t22-,23-,24+,25+,26-,27+,28+,29-,30+,32-,33+,34-,35+,36-,38+,39-,40-,41-/m1/s1
InChIKey
RXZBMPWDPOLZGW-XMRMVWPWSA-N
CAS Number
CAS 80214-83-1
ChEBI ID
CHEBI:48935
TTD Drug ID
D0Y4FL
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cyclophosphamide      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
                    In-vitro Model P388 CVCL_7222 Mouse lymphoma Mus musculus
                    Experimental
                    Result(s)		 The combination cyclophosphamide and roxithromycin, but not the individual compounds, is toxic to endothelial cells by inducing apoptosis.
Target and Pathway
Target(s) Bacterial 50S ribosomal RNA (Bact 50S rRNA)  Molecule Info  [3]
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1465).
Reference 2 Mechanisms of venoocclusive disease resulting from the combination of cyclophosphamide and roxithromycin. Ther Drug Monit. 2006 Dec;28(6):766-74.
Reference 3 Molecular insights into 14-membered macrolides using the MM-PBSA method. J Chem Inf Model. 2009 Jun;49(6):1558-67.
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