NOVOBIOCIN

US Previously Marketed

First approved in 1956

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H36N2O11
Molecular Weight	612.6243
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@@H]1[C@@H](OC(N)=O)[C@@H](O)[C@H](OC2=CC=C3C(O)=C(NC(=O)C4=CC(CC=C(C)C)=C(O)C=C4)C(=O)OC3=C2C)OC1(C)C

InChI

InChIKey=YJQPYGGHQPGBLI-KGSXXDOSSA-N

InChI=1S/C31H36N2O11/c1-14(2)7-8-16-13-17(9-11-19(16)34)27(37)33-21-22(35)18-10-12-20(15(3)24(18)42-28(21)38)41-29-23(36)25(43-30(32)39)26(40-6)31(4,5)44-29/h7,9-13,23,25-26,29,34-36H,8H2,1-6H3,(H2,32,39)(H,33,37)/t23-,25+,26-,29-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB01051
Curator's Comment: description was created based on several sources, including https://www.federalregister.gov/documents/2011/01/19/2011-1000/determination-that-albamycin-novobiocin-sodium-capsule-250-milligrams-was-withdrawn-from-sale-for | https://www.ncbi.nlm.nih.gov/pubmed/3036023

Novobiocin (also known as streptonivicin) is an aminocoumarin antibiotic, active against Staphylococcus epidermidis. Novobiocin and other aminocoumarin antibiotics act as a potent competitive inhibitor of DNA gyrase B. The oral form of the drug was withdrawn from the market in 1999 due to safety or effectiveness reasons. Later it was discovered that novobiocin inhibited Hsp90 and topoisomerase II, and novobiocin was investigated in clinical trials against metastatic breast cancer and non-small cell lung cancer. Topical form of novobiocin was investigated in combination with nalidixic acid for treatment of psoriasis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
HSP90 3 Target ID: CHEMBL1795086 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10945979	Inhibitor 8297
DNA gyrase subunit B 3 Target ID: Q5HK03 Gene ID: NA Gene Symbol: gyrB Target Organism: Staphylococcus epidermidis (strain ATCC 35984 / RP62A) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16569821	Inhibitor 8297	0.9 µM [IC50]
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6098161	Inhibitor 8297	300.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Staphylococcal Infections 4 Sources: https://www.federalregister.gov/documents/2011/01/19/2011-1000/determination-that-albamycin-novobiocin-sodium-capsule-250-milligrams-was-withdrawn-from-sale-for	Curative	Approved 8429	ALBAMYCIN Approved Use Treatment of serious infections due to susceptible strains of Staphylococcus aureus when other less toxic antibiotics such as the penicillins, cephalosporins, vancomycin, lincomycin, erythromycin, and the tetracyclines cannot be used. Launch Date 1964
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7738619	Primary	Phase I 428	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1646065	Primary	Phase II 1132	Unknown Approved Use Unknown
Psoriasis 84 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3036023	Primary	Not Provided 504	Unknown Approved Use Unknown
Bovine subclinical mastitis caused by Staphylococcus aureus and Streptococcus agalactiae 3 Sources: https://www.drugs.com/international/albacillin.html http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500015197.pdf	Curative	Approved 8429	ALBADRY PLUS Approved Use ALBADRY PLUS Suspension is indicated for the treatment, in dry cows only, of subclinical mastitis caused by susceptible strains of Staphylococcus aureus and Streptococcus agalactiae. Launch Date 1983

C_max

Value	Dose	Co-administered	Analyte	Population
62.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3752982	500 mg 2 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NOVOBIOCIN serum	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
407 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3752982	500 mg 2 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NOVOBIOCIN serum	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.85 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3752982	500 mg 2 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NOVOBIOCIN serum	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8243034	unknown, unknown		NOVOBIOCIN serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 g 1 times / day steady, oral Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4952370	unhealthy Health Status: unhealthy Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/4952370	Other AEs: Jaundice... Other AEs: Jaundice (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/4952370

AEs

AE	Significance	Dose	Population
Jaundice	1 patient	2 g 1 times / day steady, oral Dose: 2 g, 1 times / day Route: oral Route: steady Dose: 2 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4952370	unhealthy Health Status: unhealthy Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/4952370

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 OAT1 599 OAT3 642 OAT4 146 OATP1B1 788 OATP1B3 706 OATP2B1 123

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14618629/ \| https://pubmed.ncbi.nlm.nih.gov/16490770/	yes [IC50 12.6 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19282394/	yes [IC50 34.76 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19282394/	yes [IC50 4.99 uM]
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19282394/	yes [IC50 92.68 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	yes
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	yes
OATP2B1 126	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22541068/	yes

Sourcing

Vendor/Aggregator	ID	URL
Alfa Chemistry	AP303811	https://reagents.alfa-chemistry.com/product/novobiocin-cas-303-81-1-9546.html
Aurora Fine Chemicals LLC	A17.945.044	http://online.aurorafinechemicals.com/info?ID=A17.945.044
Aurora Fine Chemicals LLC	K16.744.323	http://online.aurorafinechemicals.com/info?ID=K16.744.323
Avantor Inc	101095-654	https://us.vwr.com/store/catalog/product.jsp?catalog_number=101095-654
BLD Pharm	BD398175	http://www.bldpharm.com/products/303-81-1.html
BioSynth	W-204218	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-204218.html
ChemMol	49416161	http://www.chemmol.com/chemmol/49416161.html
Chemspace	CSSS00116206865	https://chem-space.com/CSSS00116206865
DC Chemicals	DC37392	http://www.dcchemicals.com//product_show-Novobiocin.html
Lab Network	LN00346996	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00346996
MuseChem	R060001	https://www.musechem.com/product/R060001.html
Sigma-Aldrich	PH003623_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/ph003623
Smolecule	S537551	http://www.smolecule.com/products/s537551
THE BioTek	bt-277675	https://www.thebiotek.com/product/inhibitors/bt-277675
Yuhao Chemical	XJ0599	http://www.chemyuhao.com/303-81-1.html
iChemical	EBD18381	http://www.ichemical.com/products/303-81-1.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Clinical effectiveness and safety of novobiocin.	1956 Apr	13303117
Novobiocin; absorption, diffusion, and excretion studies.	1956-1957	13425410
Novobiocin: activity in vitro and in experimental tuberculosis.	1957 Aug	13458708
Screening for new compounds with antiherpes activity.	1984 Oct	6517562
Antiviral activity and inhibition of topoisomerase by ofloxacin, a new quinolone derivative.	1987 Oct	2827566
Inhibition of HIV-1 RNA-dependent DNA polymerase and cellular DNA polymerases alpha, beta and gamma by phosphonoformic acid and other drugs.	1988 Feb	2452149
Novobiocin-induced anti-proliferative and differentiating effects in melanoma B16.	1992 Feb	1739614
In vitro activity of DNA gyrase inhibitors, singly and in combination, against Mycobacterium avium complex.	1992 May-Jun	1319302
Novobiocin is a novel inducer of CD38 on cells of the myelomonocytic lineage.	2002 Jan 30	11853877
Antimicrosporidial activity of (fluoro)quinolones in vitro and in vivo.	2005 May	16004377
Novobiocin induces apoptosis-like cell death in topoisomerase II over-expressing arsenite resistant Leishmania donovani.	2005 May	15811527
Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90.	2006 Dec 6	17132020
Discrepancy between the occurrence of Arcobacter in chickens and broiler carcass contamination.	2007 Apr	17369548
Characterization of the Arcobacter contamination on Belgian pork carcasses and raw retail pork.	2007 Aug 15	17588701
Intrinsic novobiocin resistance in Staphylococcus saprophyticus.	2007 Dec	17876001
Combinatorial biosynthesis, metabolic engineering and mutasynthesis for the generation of new aminocoumarin antibiotics.	2008	18473891
Drug-sensing hydrogels for the inducible release of biopharmaceuticals.	2008 Oct	18690239
Responsive hydrogels for label-free signal transduction within biosensors.	2010	22399885
Antibiotic Resistance in Staphylococcus aureus and Coagulase Negative Staphylococci Isolated from Goats with Subclinical Mastitis.	2010	20445785
Detection of Escherichia coli O157 and Escherichia coli O157:H7 by the immunomagnetic separation technique and stx1 and stx2 genes by multiplex PCR in slaughtered cattle in Samsun Province, Turkey.	2010 Dec	21113101
Biliary efflux transporters involved in the clearance of rosuvastatin in sandwich culture of primary rat hepatocytes.	2010 Mar	19853032
Synergistic drug combinations for tuberculosis therapy identified by a novel high-throughput screen.	2011 Aug	21576426
Aminopyrazinamides: novel and specific GyrB inhibitors that kill replicating and nonreplicating Mycobacterium tuberculosis.	2013 Mar 15	23268609

Patents

Sample Use Guides

In Vivo Use Guide

As antibiotic, novobiocin was marketed in 250 mg capsules and administered orally. For the treatment of psoriasis, novobiocin (2% or 5%) in methylcellulose were applied twice daily under occlusion.

Route of Administration: Other

In Vitro Use Guide

Minimal inhibitory concentration of novobiocin against a panel of microorganisms were determined by using the broth microdilution procedure recommended by the National Committee for Clinical Laboratory Standards.Microtiter plates (96 wells/plate; final assay volume, 100 μl per well) were inoculated with exponential-phase cells and incubated overnight at 35°C in ambient air. Wells were examined for bacterial growth by using an illuminated microtiter plate reader fitted with a magnifying mirror. MIC for Staphylococcus aureus was <= 0.06 ug/ml.

Name

Type

Language

NOVOBIOCIN

Official Name

English

BENZAMIDE, N-(7-((3-O-(AMINOCARBONYL)-6-DEOXY-5-C-METHYL-4-O-METHYL-.ALPHA.-L-LYXO-HEXOPYRANOSYL)OXY)-4-HYDROXY-8-METHYL-2-OXO-2H-1-BENZOPYRAN-3-YL)-4-HYDROXY-3-(3-METHYL-2-BUTEN-1-YL)-

Common Name

English

NOVOBIOCIN [GREEN BOOK]

Common Name

English

NOVOBIOCIN [HSDB]

Common Name

English

BENZAMIDE, N-(7-((3-O-(AMINOCARBONYL)-6-DEOXY-5-C-METHYL-4-O-METHYL-.BETA.-L-LYXO-HEXOPYRANOSYL)OXY)-4-HYDROXY-8-METHYL-2-OXO-2H-1-BENZOPYRAN-3-YL)-4-HYDROXY-3-(3-METHYL-2-BUTENYL)-

Common Name

English

Novobiocin [WHO-DD]

Common Name

English

NOVOBIOCIN [MI]

Common Name

English

NOVOBIOCIN [USP-RS]

Common Name

English

novobiocin [INN]

Common Name

English

NOVOBIOCIN [VANDF]

Common Name

English

NOVOBIOCIN [MART.]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ01XX95