TROLEANDOMYCIN

First approved in 1958

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C41H67NO15
Molecular Weight	813.97
Optical Activity	UNSPECIFIED
Defined Stereocenters	18 / 18
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@]1([H])C[C@@]2(CO2)C(=O)[C@]([H])(C)[C@]([H])([C@@]([H])(C)[C@@]([H])(C)OC(=O)[C@]([H])(C)[C@]([H])([C@]([H])(C)[C@@]1([H])O[C@@]3([H])[C@@]([H])([C@]([H])(C[C@@]([H])(C)O3)N(C)C)OC(=O)C)O[C@@]4([H])C[C@@]([H])([C@]([H])([C@]([H])(C)O4)OC(=O)C)OC)OC(=O)C

InChI

InChIKey=LQCLVBQBTUVCEQ-QTFUVMRISA-N

InChI=1S/C41H67NO15/c1-19-17-41(18-49-41)38(46)23(5)34(53-27(9)43)21(3)25(7)52-39(47)24(6)35(56-32-16-31(48-14)36(26(8)51-32)54-28(10)44)22(4)33(19)57-40-37(55-29(11)45)30(42(12)13)15-20(2)50-40/h19-26,30-37,40H,15-18H2,1-14H3/t19-,20+,21-,22+,23+,24+,25+,26-,30-,31-,32-,33-,34-,35-,36-,37+,40-,41+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C41H67NO15
Molecular Weight	813.97
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	18 / 18
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6972981 | https://www.ncbi.nlm.nih.gov/pubmed/1088733

Troleandomycin (also known Triacetyl-oleandomycin and having brand name Tao) is a macrolide antibiotic which used to for the treat of infections of the upper and lower respiratory tract: such as tonsillitis, bronchitis, sinusitis, and pneumonia. However, the brand name Tao was discontinued. Troleandomycin acts by penetrating the bacterial cell membrane and reversibly binding to the 50 S subunit of bacterial ribosomes or near the "P" or donor site so that binding of tRNA (transfer RNA) to the donor site is blocked. Translocation of peptides from the "A" or acceptor site to the "P" or donor site is prevented, and subsequent protein synthesis is inhibited.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
70S ribosome 16 Target ID: CHEMBL2363853 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6972981	Inhibitor 7701	Upper and lower respiratory tract infections

Conditions

Condition	Modality	Targets	Highest Phase	Product
Upper and lower respiratory tract infections 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1088733	Curative	70S ribosome	Approved 7997	TAO Launch Date -18921600000

Doses

Dose	Population	Adverse events
2 g multiple, oral Recommended Dose: 2 g Route: oral Route: multiple Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/3496378	unhealthy, 62 Health Status: unhealthy Age Group: 62 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3496378	Disc. AE: Hepatitis, Anicteric cholestasis... AEs leading to discontinuation/dose reduction: Hepatitis Anicteric cholestasis Sources: https://pubmed.ncbi.nlm.nih.gov/3496378

AEs

AE	Significance	Dose	Population
Anicteric cholestasis	Disc. AE	2 g multiple, oral Recommended Dose: 2 g Route: oral Route: multiple Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/3496378	unhealthy, 62 Health Status: unhealthy Age Group: 62 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3496378
Hepatitis	Disc. AE	2 g multiple, oral Recommended Dose: 2 g Route: oral Route: multiple Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/3496378	unhealthy, 62 Health Status: unhealthy Age Group: 62 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3496378

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1172	inhibitor 1318	inhibitor 1421

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 89 CYP1A2 1268 CYP2A6 594 CYP2B6 679 CYP2C8 761 CYP2C19 1215 CYP2E1 761 CYP3A5 66 P-gp 1089

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1406	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2A6 625	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2B6 845	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2C19 1277	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2C9 1362	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2D6 1455	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2E1 841	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP3A4 1462	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 4	yes [IC50 0.28 uM]
CYP3A5 119	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 4	yes [IC50 0.62 uM]
CYP1A1 188	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	yes [IC50 517.6 uM]
P-gp 1255	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/11716514/ Page: 4	yes [IC50 68.3 uM]
CYP2C8 810	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	yes [IC50 953 uM]

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:45735	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:45735
ZINC	ZINC000169307271	http://zinc15.docking.org/substances/ZINC000169307271

PubMed

Title	Date	PubMed
Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions.	2001	11735605
Clinically significant drug interactions with agents specific for migraine attacks.	2001	11460889
Coupling of a supercritical fluid chromatography system to a hybrid (Q-TOF 2) mass spectrometer: on-line accurate mass measurements.	2001	11445901
Cytochrome P4502B6 and 2C9 do not metabolize midazolam: kinetic analysis and inhibition study with monoclonal antibodies.	2001 Apr	11573629
Role of cytochrome P450 in estradiol metabolism in vitro.	2001 Feb	11741520
Troglitazone quinone formation catalyzed by human and rat CYP3A: an atypical CYP oxidation reaction.	2001 Jul 15	11389877
Indirect cytotoxicity of flucloxacillin toward human biliary epithelium via metabolite formation in hepatocytes.	2001 Jun	11409940
Comparative analysis of in vitro and in vivo pharmacokinetic parameters related to individual variability of GTS-21 in canine.	2002	15618655
Identification of a novel route of extraction of sirolimus in human small intestine: roles of metabolism and secretion.	2002 Apr	11907172
CYP3A4 active site volume modification by mutagenesis of leucine 211.	2002 Apr	11901100
Inhibition of the microsomal metabolism of 1,8-cineole in the common brushtail possum (Trichosurus vulpecula) by terpenes and other chemicals.	2002 Dec	12593759
Is quinine a suitable probe to assess the hepatic drug-metabolizing enzyme CYP3A4?	2002 Dec	12492613
Effects of olopatadine, a new antiallergic agent, on human liver microsomal cytochrome P450 activities.	2002 Dec	12433826
Enzyme kinetics for the formation of 3-hydroxyquinine and three new metabolites of quinine in vitro; 3-hydroxylation by CYP3A4 is indeed the major metabolic pathway.	2002 Dec	12433805
Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5.	2002 Dec	12433801
Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol.	2002 Dec 1	12490133
Involvement of cytochrome P450 in the metabolism of rebamipide by the human liver.	2002 Jul	12162853
CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes.	2002 Jul	12065438
Metabolism of a novel phosphodiesterase-IV inhibitor (V11294) by human hepatic cytochrome P450 forms.	2002 Jun	12160484
Paraquat detoxicative system in the mouse liver postmitochondrial fraction.	2002 Jun 1	12051692
Human cytochrome P450s involved in the metabolism of 9-cis- and 13-cis-retinoic acids.	2002 Mar 1	11911845
Cytochrome P450 3A4 and P-glycoprotein mediate the interaction between an oral erythromycin breath test and rifampin.	2002 Nov	12426516
Interaction of cytochrome P450 3A inhibitors with P-glycoprotein.	2002 Oct	12235267
Alternate treatments in asthma.	2003 Apr	12684319
Simultaneous assessment of drug interactions with low- and high-extraction opioids: application to parecoxib effects on the pharmacokinetics and pharmacodynamics of fentanyl and alfentanil.	2003 Apr	12657846
Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine.	2003 Dec 3	14652237
Inhibitory effect of troleandomycin on the metabolism of omeprazole is CYP2C19 genotype-dependent.	2003 Feb	12623762
TNF-alpha -induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent.	2003 Feb	12388057
Human liver microsomal metabolism and DNA adduct formation of the tumorigenic pyrrolizidine alkaloid, riddelliine.	2003 Jan	12693032
High-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.	2003 Jan 1	12467917
Identification of novel enzyme-prodrug combinations for use in cytochrome P450-based gene therapy for cancer.	2003 Jan 1	12464259
Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction.	2003 Jan 7	12515739
The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6.	2003 Jul	12848784
Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein.	2003 Jul	12814962
Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir.	2003 Mar	12724045
Structural insight into the role of the ribosomal tunnel in cellular regulation.	2003 May	12665853
Disposition of tacrolimus in isolated perfused rat liver: influence of troleandomycin, cyclosporine, and gg918.	2003 Nov	14570757
Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats.	2003 Nov	12944587
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.	2003 Nov 17	14612892
An evaluation of a low-density DNA microarray using cytochrome P450 inducers.	2003 Sep	12971794
Demethylation of radiolabelled dextromethorphan in rat microsomes and intact hepatocytes.	2003 Sep	12950260
Key structural features of ligands for activation of human pregnane X receptor.	2004 Apr	15039302
CYP3A4 is a human microsomal vitamin D 25-hydroxylase.	2004 Apr	15005856
Utility of microtiter plate assays for human cytochrome P450 inhibition studies in drug discovery: application of simple method for detecting quasi-irreversible and irreversible inhibitors.	2004 Feb	15499170
Large interindividual variability in the in vitro formation of tamoxifen metabolites related to the development of genotoxicity.	2004 Jan	14678348
Sulfoxidation of cysteine and mercapturic acid conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A).	2004 Mar	15025515
Intravenous and oral alfentanil as in vivo probes for hepatic and first-pass cytochrome P450 3A activity: noninvasive assessment by use of pupillary miosis.	2004 Nov	15536460
Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone.	2004 Sep	15371986
CYP3A4 is a vitamin D-24- and 25-hydroxylase: analysis of structure function by site-directed mutagenesis.	2005 Feb	15546903
Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes.	2005 Mar	15557344

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Pneumonia: 250 to 500 mg orally 4 times a day.

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Sat Jun 26 08:45:19 UTC 2021` Edited by `admin` on `Sat Jun 26 08:45:19 UTC 2021`
Record UNII	C4DZ64560D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TROLEANDOMYCIN

Official Name

English

OLEANDOMYCIN (AS TROLEANDOMYCIN)

Common Name

English

OLEANDOMYCIN (AS TROLEANDOMYCIN) [VANDF]

Common Name

English

NSC-108166

Code

English

OLEANDOMYCIN TRIACETATE ESTER

Common Name

English

TROLEANDOMYCIN [USP]

Common Name

English

TROLEANDOMYCIN [MI]

Common Name

English

TROLEANDOMYCIN [WHO-DD]

Common Name

English

TRIACETYLOLEANDOMYCIN [JAN]

Common Name

English

TROLEANDOMYCIN [ORANGE BOOK]

Common Name

English

TROLEANDOMYCIN [MART.]

Common Name

English

TROLEANDOMYCIN [VANDF]

Common Name

English

TRIACETYLOLEANDOMYCIN

Common Name

English

TROLEANDOMYCIN [INN]

Common Name

English

TROLEANDOMYCIN [USAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J01FA08