Target Information

Target General Information

Top

Target ID

T22348 (Former ID: TTDI01914)

Target Name

Bacterial DNA gyrase (Bact gyrase)

Synonyms

DNA gyrase

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Gene Name

Bact gyrA; Bact gyrB

Target Type

Successful target

[1]

Disease

[+] 8 Target-related Diseases

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

Bronchitis [ICD-11: CA20]

Glaucoma [ICD-11: 9C61]

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

Impetigo [ICD-11: 1B72]

Pneumonia [ICD-11: CA40]

Respiratory infection [ICD-11: CA07-CA4Z]

Urinary tract infection [ICD-11: GC08]

Function

DNA gyrase negatively supercoils closed circular double- stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.

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BioChemical Class

ATP-hydrolyzing DNA topoisomerase

UniProt ID

GYRA_STAAU ; GYRB_STAAU

Sequence

MAELPQSRINERNITSEMRESFLDYAMSVIVARALPDVRDGLKPVHRRILYGLNEQGMTP
DKSYKKSARIVGDVMGKYHPHGDSSIYEAMVRMAQDFSYRYPLVDGQGNFGSMDGDGAAA
MRYTEARMTKITLELLRDINKDTIDFIDNYDGNEREPSVLPARFPNLLANGASGIAVGMA
TNIPPHNLTELINGVLSLSKNPDISIAELMEDIEGPDFPTAGLILGKSGIRRAYETGRGS
IQMRSRAVIEERGGGRQRIVVTEIPFQVNKARMIEKIAELVRDKKIDGITDLRDETSLRT
GVRVVIDVRKDANASVILNNLYKQTPLQTSFGVNMIALVNGRPKLINLKEALVHYLEHQK
TVVRRRTQYNLRKAKDRAHILEGLRIALDHIDEIISTIRESDTDKVAMESLQQRFKLSEK
QAQAILDMRLRRLTGLERDKIEAEYNELLNYISELEAILADEEVLLQLVRDELTEIRDRF
GDDRRTEIQLGGFEDLEDEDLIPEEQIVITLSHNNYIKRLPVSTYRAQNRGGRGVQGMNT
LEEDFVSQLVTLSTHDHVLFFTNKGRVYKLKGYEVPELSRQSKGIPVVNAIELENDEVIS
TMIAVKDLESEDNFLVFATKRGVVKRSALSNFSRINRNGKIAISFREDDELIAVRLTSGQ
EDILIGTSHASLIRFPESTLRPLGRTATGVKGITLREGDEVVGLDVAHANSVDEVLVVTE
NGYGKRTPVNDYRLSNRGGKGIKTATITERNGNVVCITTVTGEEDLMIVTNAGVIIRLDV
ADISQNGRAAQGVRLIRLGDDQFVSTVAKVKEDAEDETNEDEQSTSTVSEDGTEQQREAV
VNDETPGNAIHTEVIDSEENDEDGRIEVRQDFMDRVEEDIQQSLDEDEE

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Drugs and Modes of Action

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Approved Drug(s)

[+] 11 Approved Drugs

Besifloxacin

Drug Info

Approved

Ocular inflammation

[1], [6]

Ciprofloxacin XR

Drug Info

Approved

Bacterial infection

[7]

Finafloxacin

Drug Info

Approved

Urinary tract infection

[7], [8]

Gatifloxacin

Drug Info

Approved

Respiratory tract infection

[4]

Grepafloxacin

Drug Info

Approved

Chronic bronchitis

[7]

Levofloxacin

Drug Info

Approved

Bacterial infection

[9]

Nemonoxacin

Drug Info

Approved

Community-acquired pneumonia

[10]

Norfloxacin

Drug Info

Approved

Bacterial infection

[11]

Ofloxacin

Drug Info

Approved

Bacterial infection

[12]

Sparfloxacin

Drug Info

Approved

Bacterial infection

[13]

Trovafloxacin

Drug Info

Approved

Bacterial infection

[14]

Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

AZD0914

Drug Info

Phase 3

Neisseria gonorrhoeae infection

[16]

BAY-35-3377

Drug Info

Phase 3

Otitis media

[17]

Zabofloxacin

Drug Info

Phase 3

Pneumonia

[18]

WCK-771

Drug Info

Phase 2

Bacterial infection

[23]

Discontinued Drug(s)

[+] 24 Discontinued Drugs

Temafloxacin

Drug Info

Withdrawn from market

Bacterial infection

[24]

OLAMUFLOXACIN MESILATE

Drug Info

Discontinued in Phase 3

Bacterial infection

[25]

99mTc-ciprofloxacin

Drug Info

Discontinued in Phase 2

Infectious disease

[28]

BAY-Y-3118

Drug Info

Discontinued in Phase 2

Bacterial infection

[29]

Cadrofloxacin

Drug Info

Discontinued in Phase 2

Bacterial infection

[30]

CFC-222

Drug Info

Discontinued in Phase 2

Bacterial infection

[31]

DANOFLOXACIN

Drug Info

Discontinued in Phase 2

Bacterial infection

[32]

DX-619

Drug Info

Discontinued in Phase 2

Bacterial infection

[33]

Ro-23-9424

Drug Info

Discontinued in Phase 2

Bacterial infection

[34]

AZD-5099

Drug Info

Discontinued in Phase 1

Infectious disease

[35]

Cetefloxacin

Drug Info

Discontinued in Phase 1

Bacterial infection

[36]

DV-7751A

Drug Info

Discontinued in Phase 1

Bacterial infection

[37]

GSK945237

Drug Info

Discontinued in Phase 1

Bacterial infection

[38]

PD-131112

Drug Info

Discontinued in Phase 1

Bacterial infection

[39]

BMY-40062

Drug Info

Terminated

Bacterial infection

[42]

CBR-2092

Drug Info

Terminated

Bacterial infection

[43]

Clinafloxacin

Drug Info

Terminated

Pneumonia

[44]

CP-67015

Drug Info

Terminated

Bacterial infection

[45]

KB-5246

Drug Info

Terminated

Bacterial infection

[46]

MF-5137

Drug Info

Terminated

Staphylococcus infection

[47]

PD-117596

Drug Info

Terminated

Bacterial infection

[48]

Protosufloxacin

Drug Info

Terminated

Bacterial infection

[49]

Ro-23-7777

Drug Info

Terminated

Fungal infection

[50]

S-34109

Drug Info

Terminated

Staphylococcus infection

[51]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

Viquidacin

Drug Info

Preclinical

Bacterial infection

[40]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 39 Modulator drugs

Besifloxacin

Drug Info

[1], [6]

Ciprofloxacin XR

Drug Info

[52], [53]

Finafloxacin

Drug Info

[8], [54]

Gatifloxacin

Drug Info

[52]

Grepafloxacin

Drug Info

[55]

Levofloxacin

Drug Info

[52]

Norfloxacin

Drug Info

[52]

Ofloxacin

Drug Info

[52]

Sparfloxacin

Drug Info

[52]

Trovafloxacin

Drug Info

[52]

AZD0914

Drug Info

[56]

Zabofloxacin

Drug Info

[58]

WCK-771

Drug Info

[59], [60]

Temafloxacin

Drug Info

[61]

OLAMUFLOXACIN MESILATE

Drug Info

[62]

BAY-Y-3118

Drug Info

[64]

Cadrofloxacin

Drug Info

[65]

CFC-222

Drug Info

[66]

DANOFLOXACIN

Drug Info

[67]

DX-619

Drug Info

[68]

Ro-23-9424

Drug Info

[69]

AZD-5099

Drug Info

[70]

Cetefloxacin

Drug Info

[62]

DV-7751A

Drug Info

[71]

GSK945237

Drug Info

[72]

PD-131112

Drug Info

[62]

Viquidacin

Drug Info

[73]

BMY-40062

Drug Info

[74]

CBR-2092

Drug Info

[75]

Clinafloxacin

Drug Info

[76]

CP-67015

Drug Info

[52]

KB-5246

Drug Info

[77]

MF-5137

Drug Info

[52]

PD-117596

Drug Info

[78]

Protosufloxacin

Drug Info

[52]

Ro-23-7777

Drug Info

[52]

S-34109

Drug Info

[79]

NSFQ-105

Drug Info

[80]

PD-117558

Drug Info

[81]

Inhibitor

[+] 3 Inhibitor drugs

Nemonoxacin

Drug Info

[10]

BAY-35-3377

Drug Info

[57]

99mTc-ciprofloxacin

Drug Info

[63]

Drug Property Profile of Target

Top

(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

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.

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

REF 5

Prulifloxacin: a new antibacterial fluoroquinolone. Expert Rev Anti Infect Ther. 2006 Feb;4(1):27-41.

REF 6

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

REF 7

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

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

Nemonoxacin: first global approval. Drugs. 2014 Aug;74(12):1445-53.

REF 11

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 074690.

REF 12

Emerging therapies for the treatment and prevention of otitis media. Expert Opin Emerg Drugs. 2006 May;11(2):251-64.

REF 13

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

REF 14

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050762.

REF 15

ClinicalTrials.gov (NCT03696342) Efficacy of the Ophthalmic Pazufloxacin 0.6% for Bacterial Conjunctivitis, Compared to Gatifloxacin 0.3%. (PRO-157). U.S. National Institutes of Health.

REF 16

ClinicalTrials.gov (NCT03959527) Zoliflodacin in Uncomplicated Gonorrhoea. U.S. National Institutes of Health.

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 800012837)

REF 18

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 19

ClinicalTrials.gov (NCT03964493) TNP-2092 to Treat Acute Bacterial Skin and Skin Structure Infection (P2_ABSSSI). U.S. National Institutes of Health.

REF 20

ClinicalTrials.gov (NCT01198626) Efficacy and Safety Study of JNJ-32729463 Compared With Moxifloxacin for the Treatment of Subjects Requiring Hospitalization for Community-Acquired Bacterial Pneumonia. U.S. National Institutes of Health.

REF 21

ClinicalTrials.gov (NCT03900676) Efficacy and Safety Study of VB-1953 Topical Gel for Inflammatory Facial Acne Vulgaris. U.S. National Institutes of Health.

REF 22

ClinicalTrials.gov (NCT02537847) Sitafloxacin and Ertapenem Treatment for Acute Pyelonephritis Caused by Escherichia Coli (SETAP). U.S. National Institutes of Health.

REF 23

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 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000542)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006301)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004009)

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004047)

REF 28

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016416)

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001782)

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002693)

REF 31

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004010)

REF 32

Pharmacokinetic and pharmacodynamic profiles of danofloxacin administered by two dosing regimens in calves infected with Mannheimia (Pasteurella) haemolytica. Antimicrob Agents Chemother. 2002 Sep;46(9):3013-9.

REF 33

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 34

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000529)

REF 35

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034406)

REF 36

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001898)

REF 37

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002052)

REF 38

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027355)

REF 39

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001614)

REF 40

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017450)

REF 41

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001978)

REF 42

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000465)

REF 43

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 44

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000525)

REF 45

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003590)

REF 46

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000463)

REF 47

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004011)

REF 48

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000523)

REF 49

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003745)

REF 50

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003620)

REF 51

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007670)

REF 52

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

REF 53

DOI: 10.1093/jac/48.4.479

REF 54

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 55

Grepafloxacin, a dimethyl derivative of ciprofloxacin, acts preferentially through gyrase in Streptococcus pneumoniae: role of the C-5 group in tar... Antimicrob Agents Chemother. 2002 Feb;46(2):582-5.

REF 56

High in vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug-resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea.Antimicrob Agents Chemother.2014 Sep;58(9):5585-8.

REF 57

Antibiotics in the clinical pipeline in 2013. J Antibiot (Tokyo). 2013 Oct;66(10):571-91.

REF 58

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

REF 59

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

REF 60

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.

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Mechanisms and frequency of resistance to temafloxacin. Am J Med. 1991 Dec 30;91(6A):27S-30S.

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Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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Binding of ciprofloxacin labelled with technetium Tc 99m versus 99mTc-pertechnetate to a live and killed equine isolate of Escherichia coli. Can J Vet Res. 2005 October; 69(4): 272-277.

REF 64

Bay Y 3118, a new quinolone derivative, rapidly eradicates Listeria monocytogenes from infected mice and L929 cells.

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Hydrophilicity of quinolones is not an exclusive factor for decreased activity in efflux-mediated resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother. 1996 Aug;40(8):1835-42.

REF 66

Fluoroquinolone resistance in Mycoplasma gallisepticum: DNA gyrase as primary target of enrofloxacin and impact of mutations in topoisomerases on r... J Antimicrob Chemother. 2002 Oct;50(4):589-92.

REF 67

Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows. J Vet Pharmacol Ther. 1998 Jun;21(3):209-13.

REF 68

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 69

Mode of action of the dual-action cephalosporin Ro 23-9424. Antimicrob Agents Chemother. 1989 Jul;33(7):1067-71.

REF 70

Optimization of pyrrolamide topoisomerase II inhibitors toward identification of an antibacterial clinical candidate (AZD5099). J Med Chem. 2014 Jul 24;57(14):6060-82.

REF 71

Antimicrobial activity of DV-7751a, a new fluoroquinolone.

REF 72

Company report (gsk)

REF 73

Selenophene-containing inhibitors of type IIA bacterial topoisomerases.J Med Chem.2011 May 12;54(9):3418-25.

REF 74

Relationships among antibacterial activity, inhibition of DNA gyrase, and intracellular accumulation of 11 fluoroquinolones. Antimicrob Agents Chemother. 1992 Dec;36(12):2622-7.

REF 75

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 76

DNA gyrase and topoisomerase IV are dual targets of clinafloxacin action in Streptococcus pneumoniae. Antimicrob Agents Chemother. 1998 Nov;42(11):2810-6.

REF 77

Activity of KB-5246 against outer membrane mutants of Escherichia coli and Salmonella typhimurium.. Antimicrob Agents Chemother. 1990 July; 34(7): 1323-1325.

REF 78

In vitro antibacterial activities of the fluoroquinolones PD 117596, PD 124816, and PD 127391. Diagn Microbiol Infect Dis. 1991 May-Jun;14(3):245-58.

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Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007670)

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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 81

1-Substituted 7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8- difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids.New quantitative structure-activity relationships at N1 for the quinolone antibacterials.J Med Chem.1988 May;31(5):991-1001.

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