Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUWYEA)

• DTT Name: Bacterial 50S ribosomal RNA (Bact 50S rRNA)
• Gene Name: NO-GeName
• DTT Type: Successful target; [1]
• Related Disease:
  Acne vulgaris [ICD-11: ED80]
  Bacterial infection [ICD-11: 1A00-1C4Z]
  Gram-positive bacterial infection [ICD-11: 1B74-1F40]
  Impetigo [ICD-11: 1B72]
  Skin and skin-structure infection [ICD-11: 1F28-1G0Z]
  Syphilis [ICD-11: 1A61-1A6Z]
• UniProt ID: NOUNIPROTAC
• TTD ID: T53601
• Function: Protein L1 is also a translational repressor protein, it controls the translation of the L11 operon by binding to its mRNA.

Molecular Interaction Atlas (MIA) of This DTT

13 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clarithromycin	DM4M1SG	Bacterial infection	1A00-1C4Z	Approved	[2]
Clindamycin	DM15HL8	Acne vulgaris	ED80	Approved	[2]
Dalfopristin	DM4LTKV	Bacterial infection	1A00-1C4Z	Approved	[3]
Dirithromycin	DM0D9YJ	Bacterial infection	1A00-1C4Z	Approved	[4]
Erythromycin	DM4K7GQ	Bacterial infection	1A00-1C4Z	Approved	[5], [6], [2]
Gentamicine sulfate	DMBT7MI	Bacterial infection	1A00-1C4Z	Approved	[7]
Josamycin	DMKJ8LB	Bacterial infection	1A00-1C4Z	Approved	[8]
Lincomycin	DMVTHER	Gram-positive bacterial infection	1B74-1G40	Approved	[9]
Retapamulin	DM9JXB7	Impetigo	1B72	Approved	[10]
Tedizolid	DMG2SKR	Skin infection	1F28-1G0Z	Approved	[1]
Telithromycin	DMZ4P3A	Bacterial infection	1A00-1C4Z	Approved	[11], [12]
Troleandomycin	DMUZNIG	Bacterial infection	1A00-1C4Z	Approved	[13]
Zithromax	DMN4H2O	Syphilis infection	1A6Z	Approved	[14]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DARE-BV1	DM1C95G	Bacterial vaginosis	MF3A	Phase 3	[15]
Solithromycin	DM6QZIA	Bacillus anthracis infection	1G40	Phase 3	[16]
BC-7013	DMMKCJ6	Skin infection	1F28-1G0Z	Phase 2	[17]
GSK-1399686	DM6HBGN	Inflammatory bowel disease	DD72	Phase 2	[18]
BC-3205	DMGFABM	Respiratory tract infection	CA45	Phase 1	[19]

6 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Roxithromycin	DMVMIK2	Bacterial infection	1A00-1C4Z	Withdrawn from market	[20]
Azithromycin/chloroquine	DM7G8T0	Bacterial infection	1A00-1C4Z	Discontinued in Phase 3	[21], [22]
Eperezolid	DMCU1WO	Bacterial infection	1A00-1C4Z	Discontinued in Phase 3	[23]
Evernimicin	DM159U2	Bacterial infection	1A00-1C4Z	Discontinued in Phase 3	[24]
HMR-3562	DMKA612	Bacterial infection	1A00-1C4Z	Discontinued in Phase 1	[25]
HMR-3787	DMCHFIT	Bacterial infection	1A00-1C4Z	Terminated	[25]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RANBEZOLID HYDROCHLORIDE	DMRZBM7	Bacterial infection	1A00-1C4Z	Preclinical	[26]
RX-01-423	DM3AIQO	Bacterial infection	1A00-1C4Z	Preclinical	[27]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Erythromycin salnacedin	DM0PHEW	Discovery agent	N.A.	Investigative	[14]

References

• [1] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [2] Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
• [3] The streptogramin antibiotics: update on their mechanism of action. Expert Opin Investig Drugs. 1998 Apr;7(4):591-9.
• [4] Review of macrolides and ketolides: focus on respiratory tract infections. Drugs. 2001;61(4):443-98.
• [5] 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.
• [6] Inhibition of 50S ribosomal subunit assembly in Haemophilus influenzae cells by azithromycin and erythromycin. Curr Microbiol. 2002 Jun;44(6):418-24.
• [7] The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo. J Mol Biol. 2002 Sep 13;322(2):273-9.
• [8] The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome. J Mol Biol. 2003 Jul 25;330(5):1005-14.
• [9] Specific inhibition of 50S ribosomal subunit formation in Staphylococcus aureus cells by 16-membered macrolide, lincosamide, and streptogramin B antibiotics. Curr Microbiol. 2000 Aug;41(2):126-35.
• [10] Retapamulin inhibition of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells. Antimicrob Agents Chemother. 2007 Sep;51(9):3385-7.
• [11] 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.
• [12] Clinical pharmacokinetics of telithromycin, the first ketolide antibacterial. Clin Pharmacokinet. 2005;44(9):915-34.
• [13] Depression of colony formation by human thymus-derived lymphocytes with rifampin and other antimicrobial agents. J Infect Dis. 1981 Jun;143(6):832-5.
• [14] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [15] Characterization of Escherichia coli 50S ribosomal protein L31. FEMS Microbiol Lett. 1999 Nov 15;180(2):345-9.
• [16] Company report (cempra)
• [17] Company report (briva)
• [18] Current, new and future biological agents on the horizon for the treatment of inflammatory bowel diseases. Therap Adv Gastroenterol. 2015 March; 8(2): 66-82.
• [19] Disk Diffusion and MIC Quality Control Ranges for BC-3205 and BC-3781, Two Novel Pleuromutilin Antibiotics. J Clin Microbiol. 2012 October; 50(10): 3361-3364.
• [20] Molecular insights into 14-membered macrolides using the MM-PBSA method. J Chem Inf Model. 2009 Jun;49(6):1558-67.
• [21] Pfizer. Product Development Pipeline. March 31 2009.
• [22] Time-resolved binding of azithromycin to Escherichia coli ribosomes. J Mol Biol. 2009 Jan 30;385(4):1179-92.
• [23] The oxazolidinone eperezolid binds to the 50S ribosomal subunit and competes with binding of chloramphenicol and lincomycin.
• [24] Evernimicin binds exclusively to the 50S ribosomal subunit and inhibits translation in cell-free systems derived from both gram-positive and gram-n... Antimicrob Agents Chemother. 2000 May;44(5):1121-6.
• [25] Structure-activity relationships for six ketolide antibiotics. Curr Microbiol. 2001 Mar;42(3):203-10.
• [26] Mode of Action of Ranbezolid against Staphylococci and Structural Modeling Studies of Its Interaction with Ribosomes . Antimicrob Agents Chemother. 2009 April; 53(4): 1427-1433.
• [27] DOI: 10.1038/nrd2202