SISOMICIN

US Previously Marketed

First approved in 1980

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H37N5O7
Molecular Weight	447.5264
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]3(O[C@@H]1[C@@H](N)C[C@@H](N)[C@H](O[C@@]2([H])OC[C@](C)(O)[C@H](NC)[C@H]2O)[C@H]1O)OC(CN)=CC[C@H]3N

InChI

InChIKey=URWAJWIAIPFPJE-YFMIWBNJSA-N

InChI=1S/C19H37N5O7/c1-19(27)7-28-18(13(26)16(19)24-2)31-15-11(23)5-10(22)14(12(15)25)30-17-9(21)4-3-8(6-20)29-17/h3,9-18,24-27H,4-7,20-23H2,1-2H3/t9-,10+,11-,12+,13-,14-,15+,16-,17-,18-,19+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6994206
Curator's Comment: description was created based on several sources, including http://www.drugsupdate.com/generic/view/479/Sisomicin

Sisomicin is a new broad-spectrum aminoglycoside most closely related structurally to gentamicin C1a. In vitro and in experimental infections, sisomicin has been found to be more potent than or nearly as potent as the most active of the other available aminoglycosides. Although susceptible to many (but not all) aminoglycoside-inactivating enzymes, sisomicin is active against many microorganisms that are resistant to other aminoglycosides by nonenzymatic mechanisms. Sisomicin has been shown to interact synergistically with various beta-lactam antibiotics against enterococci, staphylocicci, Enterobacteriaceae, and nonfermentative gram-negative bacilli. The pharmacokinetics and toxicity of sisomicin in humans appear to be similar to those of gentamicin, despite earlier reports of greater acute toxicity in animals. Sisomicin binds to 30s and 50s ribosomal subunits of susceptible bacteria disrupting protein synthesis, thus rendering the bacterial cell membrane defective.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial 70S ribosome 179 Target ID: CHEMBL2363135 Sources: http://www.drugsupdate.com/generic/view/479/Sisomicin	Binding Agent 1064

Conditions

Condition	Modality	Highest Phase	Product
Chest infections 2 Sources: http://www.tabletwise.com/ensamycin-cream	Curative	Approved 8429	Ensamycin Cream Approved Use Ensamycin Cream is used in the treatment, control, prevention, and improvement of the following diseases, conditions and symptoms: • Chest infections; • Bacterial infection
Bacterial infections 234 Sources: http://www.tabletwise.com/ensamycin-cream	Curative	Approved 8429	Unknown Approved Use Unknown
Urinary tract infections 205 Sources: http://www.ncbi.nlm.nih.gov/pubmed/329522	Curative	Phase I 428	Unknown Approved Use Unknown

AUC

Value	Dose	Analyte	Population
10.15 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	50 mg single, intramuscular dose: 50 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	50 mg single, intravenous dose: 50 mg route of administration: Intravenous experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
17.76 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21.52 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	100 mg single, intramuscular dose: 100 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.98 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.39 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
2.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	50 mg single, intramuscular dose: 50 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	50 mg single, intravenous dose: 50 mg route of administration: Intravenous experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.75 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	100 mg single, intramuscular dose: 100 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.89 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	25 mg single, intramuscular dose: 25 mg route of administration: Intramuscular experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.34 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7334458	25 mg single, intravenous dose: 25 mg route of administration: Intravenous experiment type: SINGLE co-administered:	SISOMICIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00C09C	https://www.aablocks.com/goods/Goods/detail?id=AA00C09C
AK Scientific, Inc. (AKSCI)	69739	http://www.aksci.com/item_detail.php?cat=69739
Aurora Fine Chemicals LLC	A30.260.887	http://online.aurorafinechemicals.com/info?ID=A30.260.887
AvaChem Scientific	3048B	http://www.avachem.com/productSearch.asp?3048B
BLD Pharm	BD151216	http://www.bldpharm.com/products/32385-11-8.html
Chemspace	CSSB00020617376	https://chem-space.com/CSSB00020617376
DC Chemicals	DC32646	http://www.dcchemicals.com//product_show-Sisomicin.html
Lab Network	LN01254476	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01254476
OChem	10368	http://www.ocheminc.com/index.php?act=psearch&pid=85S118
Smolecule	S543254	http://www.smolecule.com/products/s543254
Smolecule	S749239	https://www.smolecule.com/products/s749239
THE BioTek	bt-283357	https://www.thebiotek.com/product/inhibitors/bt-283357
iChemical	EBD2202160	http://www.ichemical.com/products/32385-11-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Hypocalcemia with hypoparathyroidism and renal tubular dysfunction associated with aminoglycoside therapy.	1977 Apr	856439
Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production.	1993 Sep 24	8402886
[Microbiological research for the Hungarian pharmaceutical industry].	2001	11769096
[Analysis of the response factors of different aminoglycoside antibiotics detected by evaporative light-scattering detector].	2002 Mar	12579763
A comparative clinical study of sisomicin cream versus mupirocin ointment in pyodermas.	2002 Mar-Apr	17656883
Transferable plasmid mediating resistance to multiple antimicrobial agents in Klebsiella pneumoniae isolates in Greece.	2002 Sep	12427218
[Evaluation of outcomes of combined specific prophylaxis with the antibiotic resistant immunogenic plague pathogen strain and emergency prophylaxis with aminoglycosides in the experimental plague model in white mice].	2003	12968464
Role of the acetyltransferase AAC(6')-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia.	2003 Apr	12654758
Novel antibiotic-resistance markers in pGK12-derived vectors for Borrelia burgdorferi.	2003 Jan 16	12559574
A new micellar electrokinetic capillary chromatography method for separation of the components of the aminoglycoside antibiotics.	2003 Sep	12973798
Determination of tobramycin in serum using liquid chromatography-tandem mass spectrometry and comparison with a fluorescence polarisation assay.	2003 Sep 5	12954384
Acid-base versus structural properties of an aminoglycoside antibiotic--sisomicin: NMR and potentiometric approach.	2004 Aug 1	15246085
Distribution and characterization of Campylobacter spp. from Russian poultry.	2004 Feb	14968953
Effectiveness of short-term antibiotic prophylaxis on postoperative recovery course after pulmonary lobectomies.	2004 Jun	15366404
Voltage-dependent inhibition of rat skeletal muscle sodium channels by aminoglycoside antibiotics.	2004 May	14963710
ATP, histidine or magnesium ions can protect DNA against sisomicin-induced damage, following stray Cu(II) binding.	2004 Nov 1	15464730
[Electrospray ion trap mass spectrometry of eight aminoglycoside antibiotics].	2004 Oct	15700825
[Study on cloning of sisomicin-resistant gene (sisR) from Micromonospora inyoensis].	2005 Jan	15859346
Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in community-acquired primary pyoderma.	2006 Mar-Apr	16707818
Inhibition of the catalytic activity of trans-acting antigenomic delta ribozyme by selected antibiotics and their Cu2+ complexes.	2006 Nov 3	16979585
16S rRNA methylase-producing, gram-negative pathogens, Japan.	2007 Apr	17553289
Evaluation of combined deactivators-supplemented agar medium (CDSAM) for recovery of dermatophytes from patients with tinea pedis.	2007 Jun	17510857
Inhibition of poly(A) polymerase by aminoglycosides.	2007 Oct	17629605
Aminoglycoside resistance in members of the Staphylococcus sciuri group.	2007 Summer	17650957
Micellar electrokinetic chromatography of aminoglycosides.	2008	18392592
Improved liquid chromatographic method with pulsed electrochemical detection for the analysis of gentamicin.	2008 May 2	18199440
Characterization of impurities in sisomicin and netilmicin by liquid chromatography/mass spectrometry.	2008 Nov	18853394
Evaluation of the stability of gentamicin in different antibiotic carriers using a validated MEKC method.	2008 Nov 4	18639995
Deep recurrent infection of the hip after tumoral resection in an 18-years old male--a case report.	2008 Oct-Dec	20108525
Development of a non-derivatization high-performance liquid chromatography method with resonance Rayleigh scattering detection for the detection of sisomicin in rat serum.	2009 Dec 1	19889588
Identification of gentamicin impurities by liquid chromatography tandem mass spectrometry.	2009 Dec 5	19577403
Synthesis and comparative antibacterial activity of verdamicin C2 and C2a. A new oxidation of primary allylic azides in dihydro[2H]pyrans.	2009 Jan 15	19072132
Molecular cloning and sequence analysis of the sisomicin biosynthetic gene cluster from Micromonospora inyoensis.	2009 Mar	19039528
[Antibiotics given subcutaneously to elderly].	2009 Mar	18996679
Contact sensitization in venous eczema: preliminary results of patch testing with Indian standard series and topical medicaments.	2009 Mar-Apr	19293499
Genetic analysis of antimicrobial resistance in Escherichia coli isolated from diarrheic neonatal calves.	2009 May 12	19128900
Characterization and identification of a novel marine Streptomyces sp. produced antibacterial substance.	2009 Nov-Dec	19277782
Characterization of the enzyme aac(3)-Id in a clinical isolate of Salmonella enterica serovar Haifa causing traveler's diarrhea.	2009 Oct	19403206
Inactivation of the Ecs ABC transporter of Staphylococcus aureus attenuates virulence by altering composition and function of bacterial wall.	2010 Dec 2	21151985
Immunoassays for the rapid detection of gentamicin and micronomicin in swine muscle.	2010 Jan-Feb	20334196
Determination of aminoglycoside and macrolide antibiotics in meat by pressurized liquid extraction and LC-ESI-MS.	2010 Mar	20155746
Biomimetic synthesis and structural refinement of the macrocyclic dimer aminoglycoside 66-40C--the remarkably selective self-condensation of a putative aldehyde intermediate in the submerged culture medium producing sisomicin.	2010 Mar 28	20221476
Thermodynamics and kinetics of association of antibiotics with the aminoglycoside acetyltransferase (3)-IIIb, a resistance-causing enzyme.	2010 May 18	20387903
Combating evolution with intelligent design: the neoglycoside ACHN-490.	2010 Oct	20932796
Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia coli and Klebsiella pneumoniae from New York City.	2010 Oct	20667885
Discovery of selective bioactive small molecules by targeting an RNA dynamic ensemble.	2011 Jun 26	21706033

Patents

Sample Use Guides

In Vivo Use Guide

Adult: IM- Susceptible infections- 3 mg/kg/day in 2-3 divided doses. Ophthalmic- Instill one or two drops into the affected eyes. Toical-As 0.1% cream: Apply twice daily.

Route of Administration: Other

In Vitro Use Guide

540 strains of bacteria isolated from various clinical materials comprising 440 strains of Gram negative bacilli and 100 strains of Gram positive cocci were tested for their susceptibility in vitro to Sisomicin (Ensamycin). The sensitivity pattern revealed that 89.0% of the strains were sensitive to Sisomicin. The effectiveness of Sisomicin is comparatively greater (6.1%) than the other two aminoglycosides.

Name

Type

Language

SISOMICIN

Official Name

English

(2S-CIS)-4-O-(3-AMINO-6-(AMINOMETHYL)-3,4-DIHYDRO-2H-PYRAN-2-YL)-2-DEOXY-6-O-(3-DEOXY-4-C-METHYL-3-(METHYLAMINO)-.BETA.-L-ARABINOPYRANOSYL)-D-STREPTAMINE

Common Name

English

2-DEOXY-4-O-(3-DEOXY-4-C-METHYL-3-(METHYLAMINO)-.BETA.-L-ARABINOPYRANOSYL)-6-O-(2,6-DIAMINO-2,3,4,6-TETRADEOXY-.ALPHA.-D-GLYCERO-HEX-4-ENOPYRANOSYL)-L-STREPTAMINE

Systematic Name

English

SISOMICIN [USAN]

Common Name

English

SISOMICIN [MI]

Common Name

English

GENTAMICIN SULFATE IMPURITY A [EP IMPURITY]

Common Name

English

NETILMICIN SULFATE IMPURITY A [EP IMPURITY]

Common Name

English

SCH 13475

Code

English

O-3-DEOXY-4-C-METHYL-3-(METHYLAMINO)-.BETA-L-ARABINOPYRANOSYL-(1->4)-O-(2,6-DIAMINO-2,3,4,6-TETRADEOXY-.ALPHA.-D-GLYCERO-HEX-4-ENOPYRANOSYL-(1->6))-2-DEOXY-L-STREPTAMINE

Common Name

English

RICKAMICIN

Common Name

English

Sisomicin [WHO-DD]

Common Name

English

sisomicin [INN]

Common Name

English

SISSOMICIN

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ01GB08