General Information of Drug (ID: DMVMIK2)

Drug Name
Roxithromycin
Synonyms
Assoral; Overall; RXM; Rossitrol; Roxithromycine; Roxithromycinum; Roxitromicina; Rulid; Rulide; Surlid; Roxithromycine [French]; Roxithromycinum [Latin]; Roxitromicina [Spanish]; RC2952; RU 28965; RU 965; Biaxsig (TN); Coroxin (TN); RU-28965; RU-965; Roxar (TN); Roximycin (TN); Roxithromycin & Tumor Necrosis Factor; Roxo (TN); Rulide (TN); Surlid (TN); Tirabicin (TN); Roxithromycin [USAN:INN:JAN]; Roxl-150 (TN); Roxithromycin (JP15/USAN/INN); Erythromycin 9-(-O-[2-methoxyethoxy]methyloxime);Erythromycin 9-(O-((2-methoxyethoxy)methyl)oxime); Erythromycin, 9-(O-((2-methoxyethoxy)methyl)oxime); 9-(O-((2-Methoxyethoxy)methyl)oxime)erythromycin; 9-[O-(2-methoxyethoxymethyl)-oxime] of erythromycin
Indication
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Withdrawn from market [1], [2]
Therapeutic Class
Antibiotics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 837
Topological Polar Surface Area (xlogp) 3.1
Rotatable Bond Count (rotbonds) 13
Hydrogen Bond Donor Count (hbonddonor) 5
Hydrogen Bond Acceptor Count (hbondacc) 17
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
Elimination
12% of drug is excreted from urine in the unchanged form [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 12 hours [4]
Metabolism
The drug is metabolized via the hepatic [5]
Water Solubility
The ability of drug to dissolve in water is measured as 0.1 mg/mL [3]
Chemical Identifiers
Formula
C41H76N2O15
IUPAC Name
(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-(2-methoxyethoxymethoxyimino)-3,5,7,9,11,13-hexamethyl-oxacyclotetradecan-2-one
Canonical SMILES
CC[C@@H]1[C@@]([C@@H]([C@H](/C(=N/OCOCCOC)/[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)O)C)C)O)(C)O
InChI
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
Cross-matching ID
PubChem CID
6915744
ChEBI ID
CHEBI:48935
CAS Number
80214-83-1
DrugBank ID
DB00778
TTD ID
D0Y4FL
VARIDT ID
DR00708
INTEDE ID
DR1448

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bacterial 50S ribosomal RNA (Bact 50S rRNA) TTUWYEA NOUNIPROTAC Inhibitor [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

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).
2 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 BDDCS applied to over 900 drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
6 Molecular insights into 14-membered macrolides using the MM-PBSA method. J Chem Inf Model. 2009 Jun;49(6):1558-67.
7 Differences in assessment of macrolide interaction with human MDR1 (ABCB1, P-gp) using rhodamine-123 efflux, ATPase activity and cellular accumulation assays. Eur J Pharm Sci. 2010 Sep 11;41(1):86-95.
8 Hepatic veno-occlusive disease associated with immunosuppressive cyclophosphamide dosing and roxithromycin. Ann Pharmacother. 2006 Apr;40(4):767-70.
9 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
10 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
11 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
12 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
13 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
14 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
15 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
16 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
17 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
18 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
19 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
20 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
21 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
22 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
23 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
24 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
25 A synthetic alanyl-initiator tRNA with initiator tRNA properties as determined by fluorescence measurements: comparison to a synthetic alanyl-elongator tRNA. Nucleic Acids Res. 1991 Oct 25;19(20):5749-54.
26 An examination of the differential sensitivity to ketolide antibiotics in ermB strains of Streptococcus pyogenes and Streptococcus pneumoniae. Curr Microbiol. 2004 Oct;49(4):239-47.
27 Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
28 Review of macrolides and ketolides: focus on respiratory tract infections. Drugs. 2001;61(4):443-98.
29 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
30 Depression of colony formation by human thymus-derived lymphocytes with rifampin and other antimicrobial agents. J Infect Dis. 1981 Jun;143(6):832-5.
31 Retapamulin inhibition of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells. Antimicrob Agents Chemother. 2007 Sep;51(9):3385-7.
32 The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs. 1998 Apr;7(4):591-9.
33 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.