Target Information

Target General Information

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Target ID

T40696 (Former ID: TTDS00083)

Target Name

Staphylococcus Topoisomerase IV (Stap-coc parC)

Synonyms

Topoisomerase IV subunit A; DNA topoisomerase 4 subunit A

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Gene Name

Stap-coc parC

Target Type

Successful target

[1]

Disease

[+] 7 Target-related Diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Glaucoma [ICD-11: 9C61]

Gram-positive bacterial infection [ICD-11: 1B74-1F40]

Impetigo [ICD-11: 1B72]

Respiratory infection [ICD-11: CA07-CA4Z]

Skin and skin-structure infection [ICD-11: 1F28-1G0Z]

Urinary tract infection [ICD-11: GC08]

Function

Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.

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BioChemical Class

Topoisomerase GyrA ParC

UniProt ID

PARC_STAAS

EC Number

EC 5.6.2.3

Sequence

MSEIIQDLSLEDVLGDRFGRYSKYIIQERALPDVRDGLKPVQRRILYAMYSSGNTHDKNF
RKSAKTVGDVIGQYHPHGDSSVYEAMVRLSQDWKLRHVLIEMHGNNGSIDNDPPAAMRYT
EAKLSLLAEELLRDINKETVSFIPNYDDTTLEPMVLPSRFPNLLVNGSTGISAGYATDIP
PHNLAEVIQATLKYIDNPDITVNQLMKYIKGPDFPTGGIIQGIDGIKKAYESGKGRIIVR
SKVEEETLRNGRKQLIITEIPYEVNKSSLVKRIDELRADKKVDGIVEVRDETDRTGLRIA
IELKKDVNSESIKNYLYKNSDLQISYNFNMVAISDGRPKLMGIRQIIDSYLNHQIEVVAN
RTKFELDNAEKRMHIVEGLIKALSILDKVIELIRSSKNKRDAKENLIEVYEFTEEQAEAI
VMLQLYRLTNTDIVALEGEHKELEALIKQLRHILDNHDALLNVIKEELNEIKKKFKSERL
SLIEAEIEEIKIDKEVMVPSEEVILSMTRHGYIKRTSIRSFNASGVEDIGLKDGDSLLKH
QEVNTQDTVLVFTNKGRYLFIPVHKLADIRWKELGQHVSQIVPIEEDEVVINVFNEKDFN
TDAFYVFATQNGMIKKSTVPLFKTTRFNKPLIATKVKENDDLISVMRFEKDQLITVITNK
GMSLTYNTSELSDTGLRAAGVKSINLKAEDFVVVTEGVSENDTILMATQRGSLKRISFKI
LQVAKRAQRGITLLKELKKNPHRIVAAHVVTGEHSQYTLYSKSNEEHGLINDIHKSEQYT
NGSFIVDTDDFGEVIDMYIS

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Drugs and Modes of Action

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Approved Drug(s)

[+] 7 Approved Drugs

Besifloxacin

Drug Info

Approved

Ocular inflammation

[1], [5]

Ciprofloxacin XR

Drug Info

Approved

Bacterial infection

[6]

Delafloxacin Meglumine

Drug Info

Approved

Acute bacterial skin infection

[7]

Finafloxacin

Drug Info

Approved

Urinary tract infection

[6], [8]

Gatifloxacin

Drug Info

Approved

Respiratory tract infection

[4]

Levofloxacin

Drug Info

Approved

Bacterial infection

[9]

Sparfloxacin

Drug Info

Approved

Bacterial infection

[10]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

Nemonaxacin

Drug Info

Phase 3

Methicillin-resistant staphylococci infection

[12]

Zabofloxacin

Drug Info

Phase 3

Pneumonia

[13]

WCK-2349

Drug Info

Phase 2

MRSA infection

[14]

WCK-771

Drug Info

Phase 2

Bacterial infection

[15]

WCK-1152

Drug Info

Phase 1

Respiratory tract inflammation

[16]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

Avarofloxacin

Drug Info

Discontinued in Phase 2

Bacterial pneumonia

[17]

DX-619

Drug Info

Discontinued in Phase 2

Bacterial infection

[18]

DK-507k

Drug Info

Discontinued in Phase 1

Bacterial infection

[19]

CBR-2092

Drug Info

Terminated

Bacterial infection

[20]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 16 Modulator drugs

Besifloxacin

Drug Info

[1], [5]

Ciprofloxacin XR

Drug Info

[21], [22]

Finafloxacin

Drug Info

[8], [23]

Gatifloxacin

Drug Info

[21]

Levofloxacin

Drug Info

[21]

Sparfloxacin

Drug Info

[21]

Nemonaxacin

Drug Info

[24]

Zabofloxacin

Drug Info

[25]

WCK-2349

Drug Info

[26]

WCK-771

Drug Info

[27], [28]

WCK-1152

Drug Info

[29]

Avarofloxacin

Drug Info

[30]

DX-619

Drug Info

[31]

DK-507k

Drug Info

[32]

CBR-2092

Drug Info

[33]

NSFQ-105

Drug Info

[34]

Inhibitor

[+] 2 Inhibitor drugs

Delafloxacin Meglumine

Drug Info

[3]

Premafloxacin

Drug Info

[35]

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Similarity Proteins

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Similarity Proteins

There is no similarity protein (E value < 0.005) for this target

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Profiles in Patients

Top

Drug Resistance
Mutation (DRM)

Drug Resistance Mutation Info

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.

REF 2

Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.

REF 3

2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.

REF 4

Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.

REF 5

Besifloxacin ophthalmic suspension, 0.6%: a novel topical fluoroquinolone for bacterial conjunctivitis. Adv Ther. 2012 Jun;29(6):473-90.

REF 6

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 7

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018

REF 8

2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.

REF 9

How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.

REF 10

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020677.

REF 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009417)

REF 12

ClinicalTrials.gov (NCT02205112) A Phase III Study to Evaluate the Efficacy and Safety of Intravenous Infusion of Nemonoxacin in Treating CAP. U.S. National Institutes of Health.

REF 13

ClinicalTrials.gov (NCT01658020) A Study to Evaluate Efficacy and Safety Profile of Zabofloxacin Tablet 400mg and Moxifloxacin Tablet 400mg. U.S. National Institutes of Health.

REF 14

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038027)

REF 15

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016734)

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019222)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032241)

REF 18

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019670)

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016728)

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027165)

REF 21

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 22

DOI: 10.1093/jac/48.4.479

REF 23

Antibacterial activity of finafloxacin under different pH conditions against isogenic strains of Escherichia coli expressing combinations of defined mechanisms of fluoroquinolone resistance.J Antimicrob Chemother.2010 Dec;65(12):2530-3.

REF 24

In vitro activity of nemonoxacin (TG-873870), a novel non-fluorinated quinolone, against clinical isolates of Staphylococcus aureus, enterococci and Streptococcus pneumoniae with various resistance phenotypes in Taiwan.J Antimicrob Chemother.2009 Dec;64(6):1226-9.

REF 25

DNA gyrase and topoisomerase IV are dual targets of zabofloxacin in Streptococcus pneumoniae.Int J Antimicrob Agents.2010 Jul;36(1):97-8.

REF 26

DOI: 10.1038/ja.2013.86

REF 27

Antistaphylococcal Activity of WCK 771, a Tricyclic Fluoroquinolone, in Animal Infection Models

REF 28

The anti-methicillin-resistant Staphylococcus aureus quinolone WCK 771 has potent activity against sequentially selected mutants, has a narrow mutant selection window against quinolone-resistant Staphylococcus aureus, and preferentially targets DNA gyrase.Antimicrob Agents Chemother.2006 Nov;50(11):3568-79.

REF 29

DOI: 10.1093/jac/dki361

REF 30

Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2. Antimicrob Agents Chemother. 2011 Dec;55(12):5512-21.

REF 31

DX-619, a novel des-fluoro(6) quinolone manifesting low frequency of selection of resistant Staphylococcus aureus mutants: quinolone resistance beyond modification of type II topoisomerases. Antimicrob Agents Chemother. 2005 Dec;49(12):5051-7.

REF 32

In Vitro and In Vivo Antibacterial Activities of DK-507k, a Novel Fluoroquinolone

REF 33

In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus.Antimicrob Agents Chemother.2008 Jul;52(7):2313-23.

REF 34

Engineering the specificity of antibacterial fluoroquinolones: benzenesulfonamide modifications at C-7 of ciprofloxacin change its primary target i... Antimicrob Agents Chemother. 2000 Feb;44(2):320-5.

REF 35

Alteration of Escherichia coli topoisomerase IV to novobiocin resistance. Antimicrob Agents Chemother. 2003 Mar;47(3):941-7.

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