Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DME6G97)

• Drug Name: Lefamulin Drug Info
• Synonyms: UNII-21904A5386; 1061337-51-6; CHEMBL3291398; 21904A5386; Lefamulin [INN]; Acetic acid, 2-(((1R,2R,4R)-4-amino-2-hydroxycyclohexyl)thio)-, (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3ah-cyclopentacycloocten-8-yl ester; Lefamulin(BC-3781); Lefamulin [USAN:INN]; Acetic acid, 2-[[(1R,2R,4R)-4-amino-2-hydroxycyclohexyl]thio]-, (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten

Indication

Disease Entry	ICD 11	Status	REF
Community-acquired pneumonia	CA40.Z	Approved	[1]
Acute bacterial skin infection	1C41	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 25185057
  CAS Number: CAS 1061337-51-6
  TTD Drug ID: DME6G97
  INTEDE Drug ID: DR0919
  ACDINA Drug ID: D01201

Molecule-Related Drug Atlas

Drug(s) Targeting Bacterial 23S ribosomal RNA (Bact 23S rRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lopinavir	DMITQS0	Human immunodeficiency virus infection	1C62	Approved	[4]
Chloramphenicol	DMFXEWT	Bacterial infection	1A00-1C4Z	Approved	[5]
Thiamphenicol	DMDRKH2	Bacterial infection	1A00-1C4Z	Approved	[6]
Linezolid	DMGFPU2	Bacteremia	1A73	Approved	[7]
Spiramycin	DM20R5F	Bacterial infection	1A00-1C4Z	Approved	[8]
Macrolides	DM3BS97	Bacterial infection	1A00-1C4Z	Approved	[9]
Cethromycin	DMIGX84	Bacterial infection	1A00-1C4Z	Phase 3	[10]
Oxazolidinones	DMBM47Z	Gram-positive bacterial infection	1B74-1G40	Phase 2	[11]
EDP-420	DM5WZ0O	Bacterial infection	1A00-1C4Z	Phase 2	[12]
Micrococcin	DMJ4D1P	Discovery agent	N.A.	Investigative	[8]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[15]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[17]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[14]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA)	TTLFGBV	NOUNIPROTAC	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Lefamulin: review of a promising novel pleuromutilin antibiotic. Pharmacotherapy. 2018 Sep;38(9):935-946.
• [4] Company report (JMI Laboratories)
• [5] Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin. Mol Microbiol. 2004 Dec;54(5):1287-94.
• [6] The fused TrpEG from Streptomyces venezuelae is an anthranilate synthase, not a 2-amino-2-deoxyisochorismate [corrected] (ADIC) synthase. Ethn Dis. 2008 Spring;18(2 Suppl 2):S2-9-13.
• [7] Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance. Genome Res. 2009 Jul;19(7):1214-23.
• [8] The apicoplast as an antimalarial drug target. Drug Resist Updat. 2001 Jun;4(3):145-51.
• [9] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [10] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [11] Ribosomal RNA is the target for oxazolidinones, a novel class of translational inhibitors. RNA. 1999 Jul;5(7):939-46.
• [12] EDP-420, a Bicyclolide (Bridged Bicyclic Macrolide), Is Active against Mycobacterium avium. Antimicrob Agents Chemother. 2007 May; 51(5): 1666-1670.
• [13] 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.
• [14] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [15] 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.
• [16] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [17] 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.
• [18] 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.
• [19] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [20] 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.
• [21] 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.