Target Information
Target General Information | Top | |||||
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Target ID |
T40696
(Former ID: TTDS00083)
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Target Name |
Staphylococcus Topoisomerase IV (Stap-coc parC)
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Synonyms |
Topoisomerase IV subunit A; DNA topoisomerase 4 subunit A
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Gene Name |
Stap-coc parC
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 7 Target-related Diseases | + | ||||
1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
2 | Glaucoma [ICD-11: 9C61] | |||||
3 | Gram-positive bacterial infection [ICD-11: 1B74-1F40] | |||||
4 | Impetigo [ICD-11: 1B72] | |||||
5 | Respiratory infection [ICD-11: CA07-CA4Z] | |||||
6 | Skin and skin-structure infection [ICD-11: 1F28-1G0Z] | |||||
7 | 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
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UniProt ID | ||||||
EC Number |
EC 5.6.2.3
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Sequence |
MSEIIQDLSLEDVLGDRFGRYSKYIIQERALPDVRDGLKPVQRRILYAMYSSGNTHDKNF
RKSAKTVGDVIGQYHPHGDSSVYEAMVRLSQDWKLRHVLIEMHGNNGSIDNDPPAAMRYT EAKLSLLAEELLRDINKETVSFIPNYDDTTLEPMVLPSRFPNLLVNGSTGISAGYATDIP PHNLAEVIQATLKYIDNPDITVNQLMKYIKGPDFPTGGIIQGIDGIKKAYESGKGRIIVR SKVEEETLRNGRKQLIITEIPYEVNKSSLVKRIDELRADKKVDGIVEVRDETDRTGLRIA IELKKDVNSESIKNYLYKNSDLQISYNFNMVAISDGRPKLMGIRQIIDSYLNHQIEVVAN RTKFELDNAEKRMHIVEGLIKALSILDKVIELIRSSKNKRDAKENLIEVYEFTEEQAEAI VMLQLYRLTNTDIVALEGEHKELEALIKQLRHILDNHDALLNVIKEELNEIKKKFKSERL SLIEAEIEEIKIDKEVMVPSEEVILSMTRHGYIKRTSIRSFNASGVEDIGLKDGDSLLKH QEVNTQDTVLVFTNKGRYLFIPVHKLADIRWKELGQHVSQIVPIEEDEVVINVFNEKDFN TDAFYVFATQNGMIKKSTVPLFKTTRFNKPLIATKVKENDDLISVMRFEKDQLITVITNK GMSLTYNTSELSDTGLRAAGVKSINLKAEDFVVVTEGVSENDTILMATQRGSLKRISFKI LQVAKRAQRGITLLKELKKNPHRIVAAHVVTGEHSQYTLYSKSNEEHGLINDIHKSEQYT NGSFIVDTDDFGEVIDMYIS Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 10 Approved Drugs | + | ||||
1 | Besifloxacin | Drug Info | Approved | Ocular inflammation | [1], [2] | |
2 | Ciprofloxacin XR | Drug Info | Approved | Bacterial infection | [3] | |
3 | Delafloxacin Meglumine | Drug Info | Approved | Acute bacterial skin infection | [4] | |
4 | Finafloxacin | Drug Info | Approved | Urinary tract infection | [3], [5] | |
5 | Gatifloxacin | Drug Info | Approved | Respiratory tract infection | [6] | |
6 | Gemifloxacin | Drug Info | Approved | Bacterial infection | [7] | |
7 | Levofloxacin | Drug Info | Approved | Bacterial infection | [8] | |
8 | Moxifloxacin | Drug Info | Approved | Bacterial infection | [6] | |
9 | Ozenoxacin | Drug Info | Approved | Impetigo | [9] | |
10 | Sparfloxacin | Drug Info | Approved | Bacterial infection | [10] | |
Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
1 | ABT-492 | Drug Info | Phase 3 | Bacterial infection | [11] | |
2 | Nemonaxacin | Drug Info | Phase 3 | Methicillin-resistant staphylococci infection | [12] | |
3 | Zabofloxacin | Drug Info | Phase 3 | Pneumonia | [13] | |
4 | WCK-2349 | Drug Info | Phase 2 | MRSA infection | [14] | |
5 | WCK-771 | Drug Info | Phase 2 | Bacterial infection | [15] | |
6 | WCK-1152 | Drug Info | Phase 1 | Respiratory tract inflammation | [16] | |
Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
1 | Avarofloxacin | Drug Info | Discontinued in Phase 2 | Bacterial pneumonia | [17] | |
2 | DX-619 | Drug Info | Discontinued in Phase 2 | Bacterial infection | [18] | |
3 | DK-507k | Drug Info | Discontinued in Phase 1 | Bacterial infection | [19] | |
4 | CBR-2092 | Drug Info | Terminated | Bacterial infection | [20] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 20 Modulator drugs | + | ||||
1 | Besifloxacin | Drug Info | [1], [2] | |||
2 | Ciprofloxacin XR | Drug Info | [21], [22] | |||
3 | Finafloxacin | Drug Info | [5], [23] | |||
4 | Gatifloxacin | Drug Info | [21] | |||
5 | Gemifloxacin | Drug Info | [21] | |||
6 | Levofloxacin | Drug Info | [21] | |||
7 | Moxifloxacin | Drug Info | [21] | |||
8 | Ozenoxacin | Drug Info | [24] | |||
9 | Sparfloxacin | Drug Info | [21] | |||
10 | ABT-492 | Drug Info | [25] | |||
11 | Nemonaxacin | Drug Info | [26] | |||
12 | Zabofloxacin | Drug Info | [27] | |||
13 | WCK-2349 | Drug Info | [28] | |||
14 | WCK-771 | Drug Info | [29], [30] | |||
15 | WCK-1152 | Drug Info | [31] | |||
16 | Avarofloxacin | Drug Info | [32] | |||
17 | DX-619 | Drug Info | [33] | |||
18 | DK-507k | Drug Info | [34] | |||
19 | CBR-2092 | Drug Info | [35] | |||
20 | NSFQ-105 | Drug Info | [36] | |||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | Delafloxacin Meglumine | Drug Info | [9] | |||
2 | Premafloxacin | Drug Info | [37] |
Different Human System Profiles of Target | Top |
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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
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There is no similarity protein (E value < 0.005) for this target
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"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 | |||||
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Co-Targets |
Target Profiles in Patients | Top | |||||
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Drug Resistance Mutation (DRM) |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. | |||||
REF 2 | Besifloxacin ophthalmic suspension, 0.6%: a novel topical fluoroquinolone for bacterial conjunctivitis. Adv Ther. 2012 Jun;29(6):473-90. | |||||
REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2018 | |||||
REF 5 | 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. | |||||
REF 6 | Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8. | |||||
REF 7 | Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98. | |||||
REF 8 | How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73. | |||||
REF 9 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
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 and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone. J Antimicrob Chemother. 2002 Mar;49(3):455-65. | |||||
REF 25 | Contrasting Effects of Acidic pH on the Extracellular and Intracellular Activities of the Anti-Gram-Positive Fluoroquinolones Moxifloxacin and Delafloxacin against Staphylococcus aureus | |||||
REF 26 | 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 27 | DNA gyrase and topoisomerase IV are dual targets of zabofloxacin in Streptococcus pneumoniae.Int J Antimicrob Agents.2010 Jul;36(1):97-8. | |||||
REF 28 | DOI: 10.1038/ja.2013.86 | |||||
REF 29 | Antistaphylococcal Activity of WCK 771, a Tricyclic Fluoroquinolone, in Animal Infection Models | |||||
REF 30 | 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 31 | DOI: 10.1093/jac/dki361 | |||||
REF 32 | Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2. Antimicrob Agents Chemother. 2011 Dec;55(12):5512-21. | |||||
REF 33 | 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 34 | In Vitro and In Vivo Antibacterial Activities of DK-507k, a Novel Fluoroquinolone | |||||
REF 35 | 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 36 | 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 37 | Alteration of Escherichia coli topoisomerase IV to novobiocin resistance. Antimicrob Agents Chemother. 2003 Mar;47(3):941-7. |
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