TROLEANDOMYCIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C41H67NO15
Molecular Weight	813.9684
Optical Activity	UNSPECIFIED
Defined Stereocenters	18 / 18
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]2(O[C@@H]1O[C@H](C)C[C@@H]([C@H]1OC(C)=O)N(C)C)[C@@H](C)C[C@@]3(CO3)C(=O)[C@H](C)[C@@H](OC(C)=O)[C@@H](C)[C@@H](C)OC(=O)[C@H](C)[C@@]([H])(O[C@H]4C[C@H](OC)[C@@H](OC(C)=O)[C@H](C)O4)[C@@H]2C

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

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 8297

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 8429	TAO Approved Use Unknown Launch Date 1969

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 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 110 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A5 73 P-gp 1461

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	negligible [IC50 >1000 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 4.0	yes [IC50 0.28 uM]
CYP3A5 130	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15557344/ Page: 4.0	yes [IC50 0.62 uM]
CYP1A1 218	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10821163/	yes [IC50 517.6 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11716514/ Page: 4.0	yes [IC50 68.3 uM]
CYP2C8 965	inhibitor 3277 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
Identification of the human liver microsomal cytochrome P450s involved in the metabolism of N-nitrosodi-n-propylamine.	2000 Aug	10910959
Troleandomycin as an oral corticosteroid steroid sparing agent in stable asthma.	2001	11406054
Liquid chromatography of troleandomycin.	2001 Apr 20	11358231
Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6).	2001 Aug	11506127
Species difference in stereoselective involvement of CYP3A in the mono-N-dealkylation of disopyramide.	2001 Feb	11407536
Troglitazone quinone formation catalyzed by human and rat CYP3A: an atypical CYP oxidation reaction.	2001 Jul 15	11389877
Metabolism of sulfinpyrazone sulfide and sulfinpyrazone by human liver microsomes and cDNA-expressed cytochrome P450s.	2001 May	11302937
Identification of human drug-metabolizing enzymes involved in the metabolism of SNI-2011.	2001 Nov	11725960
Diazinon is activated by CYP2C19 in human liver.	2001 Nov 15	11708902
Comparative analysis of in vitro and in vivo pharmacokinetic parameters related to individual variability of GTS-21 in canine.	2002	15618655
Factors contributing to carbamazepine-macrolide interactions.	2002 Apr	12030792
CYP3A4 active site volume modification by mutagenesis of leucine 211.	2002 Apr	11901100
Effects of olopatadine, a new antiallergic agent, on human liver microsomal cytochrome P450 activities.	2002 Dec	12433826
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
Paraquat detoxicative system in the mouse liver postmitochondrial fraction.	2002 Jun 1	12051692
The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6.	2002 Mar	11854155
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
Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction.	2003 Jan 7	12515739
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
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
Role of individual human cytochrome P450 enzymes in the in vitro metabolism of hydromorphone.	2004 Apr	15268978
Immunomodulatory activity and effectiveness of macrolides in chronic airway disease.	2004 Feb	14872003
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
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
Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers.	2004 Mar	14977870
Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl citrate.	2004 Sep	15329598
CYP3A induction aggravates endotoxemic liver injury via reactive oxygen species in male rats.	2004 Sep 1	15288127
CYP3A4 is a vitamin D-24- and 25-hydroxylase: analysis of structure function by site-directed mutagenesis.	2005 Feb	15546903

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

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 IMPURITY]

Common Name

English

TROLEANDOMYCIN [MI]

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 [WHO-DD]

Common Name

English

troleandomycin [INN]

Common Name

English

TROLEANDOMYCIN [USAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J01FA08