TROLEANDOMYCIN

US Previously Marketed

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 7728

Conditions

Condition	Modality	Targets	Highest Phase	Product
Upper and lower respiratory tract infections 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1088733	Curative		Approved 8043	TAO Approved Use Unknown Launch Date -1.8921599E10

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 Page: p.327	unhealthy, 62 n = 1 Health Status: unhealthy Condition: bronchitis Age Group: 62 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3496378 Page: p.327	Disc. AE: Hepatitis, Anicteric cholestasis... AEs leading to discontinuation/dose reduction: Hepatitis Anicteric cholestasis Sources: https://pubmed.ncbi.nlm.nih.gov/3496378 Page: p.327

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 Page: p.327	unhealthy, 62 n = 1 Health Status: unhealthy Condition: bronchitis Age Group: 62 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3496378 Page: p.327
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 Page: p.327	unhealthy, 62 n = 1 Health Status: unhealthy Condition: bronchitis Age Group: 62 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3496378 Page: p.327

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1467	inhibitor 1604	inhibitor 1702

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 96 CYP1A2 1383 CYP2A6 627 CYP2B6 717 CYP2C8 818 CYP2C19 1325 CYP2E1 790 CYP3A5 70 P-gp 1330

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1532	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2A6 659	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2B6 884	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2C19 1392	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2C9 1648	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2D6 1738	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2E1 871	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP3A4 1772	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 4.0	yes [IC50 0.28 uM]
CYP3A5 122	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 4.0	yes [IC50 0.62 uM]
CYP1A1 192	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	yes [IC50 517.6 uM]
P-gp 1514	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/11716514/ Page: 4.0	yes [IC50 68.3 uM]
CYP2C8 865	inhibitor 3045 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
eMolecules	36553022	https://www.emolecules.com/cgi-bin/more?vid=36553022

PubMed

Title	Date	PubMed
Comparative analysis of in vitro and in vivo pharmacokinetic parameters related to individual variability of GTS-21 in canine.	2002	15618655
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
Effect of caffeine on acetaminophen hepatotoxicity in cultured hepatocytes treated with ethanol and isopentanol.	2002 Dec 1	12490133
Differential metabolism of midazolam in mouse liver and intestine microsomes: a comparison of cytochrome P450 activity and expression.	2003 Apr	12745872
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
Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes.	2003 Aug	12936704
Evidence for the involvement of human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein.	2003 Aug	12867277
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
Human liver microsomal metabolism and DNA adduct formation of the tumorigenic pyrrolizidine alkaloid, riddelliine.	2003 Jan	12693032
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
Upregulation of cytochromes P450 2B in rat liver by orphenadrine.	2003 Jun	12813002
In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation.	2003 Jun	12756207
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
Role of individual human cytochrome P450 enzymes in the in vitro metabolism of hydromorphone.	2004 Apr	15268978
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
Immunomodulatory activity and effectiveness of macrolides in chronic airway disease.	2004 Feb	14872003
High-throughput screening for the assessment of time-dependent inhibitions of new drug candidates on recombinant CYP2D6 and CYP3A4 using a single concentration method.	2004 Jan	14742138
Studies on the metabolism of the novel, selective cyclooxygenase-2 inhibitor indomethacin phenethylamide in rat, mouse, and human liver microsomes: identification of active metabolites.	2004 Jan	14709628
Large interindividual variability in the in vitro formation of tamoxifen metabolites related to the development of genotoxicity.	2004 Jan	14678348
Relationship between content and activity of cytochrome P450 and induction of heterocyclic amine DNA adducts in human liver samples in vivo and in vitro.	2004 Jun	15184267
Different in vitro metabolism of paclitaxel and docetaxel in humans, rats, pigs, and minipigs.	2004 Jun	15155559
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
CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes.	2004 Mar	14998425
Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers.	2004 Mar	14977870
Biochemical background of toxic interaction between tiamulin and monensin.	2004 Mar 15	15013817
Identification of cytochromes P450 2C9 and 3A4 as the major catalysts of phenprocoumon hydroxylation in vitro.	2004 May	15054565
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
Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant.	2004 Nov	15304427
Role of cytochrome P4503A in cysteine S-conjugates sulfoxidation and the nephrotoxicity of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in rats.	2004 Sep	15377151
Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone.	2004 Sep	15371986
Pharmacokinetics of clarithromycin in rats with acute renal failure induced by uranyl nitrate.	2004 Sep	15334627
Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl citrate.	2004 Sep	15329598
Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro.	2004 Sep	15327587
CYP3A induction aggravates endotoxemic liver injury via reactive oxygen species in male rats.	2004 Sep 1	15288127
Oral erythromycin and the risk of sudden death from cardiac causes.	2004 Sep 9	15356306
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. Usual Adult Dose for Streptococcal Infection: 250 to 500 mg orally 4 times a day. Usual Pediatric Dose for Pneumonia: The safety and efficacy of troleandomycin in children < 1 year have not been established. >= 1 year: 125 to 250 mg every 6 hours. When used in streptococcal infections, therapy should be continued for 10 days. Usual Pediatric Dose for Streptococcal Infection: The safety and efficacy of troleandomycin in children < 1 year have not been established. >= 1 year: 125 to 250 mg every 6 hours. When used in streptococcal infections, therapy should be continued for 10 days.

Route of Administration: Oral

In Vitro Use Guide

Unknown

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