Details of the Drug-Related molecule(s) Interaction Atlas

General Information of DTT (ID: TTN6J5F)

• DTT Name: Bacterial DNA gyrase (Bact gyrase) DTT Info
• Gene Name: Bact gyrA

Molecule-Related Drug & Molecule List

15 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Besifloxacin	DMPHXMI	Ocular inflammation	9C61.24	Approved	[1]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[2]
Finafloxacin	DMZEONG	Urinary tract infection	GC08	Approved	[3]
Gatifloxacin	DMSL679	Acute gonococcal cervicitis		Approved	[2]
Gemifloxacin	DMHT34O	Bacterial infection	1A00-1C4Z	Approved	[2]
Grepafloxacin	DMGLX0T	Chronic bronchitis	CA20.1	Approved	[4]
Levofloxacin	DMS60RB	Acute maxillary sinusitis		Approved	[2]
Moxifloxacin	DMU8V4S	Bacterial infection	1A00-1C4Z	Approved	[2]
Nemonoxacin	DM0S9Z1	Community-acquired pneumonia	CA40.Z	Approved	[5]
Norfloxacin	DMIZ6W2	Acute gonococcal cervicitis		Approved	[2]
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[2]
Ozenoxacin	DM6KZMG	Impetigo	1B72	Approved	[6]
Prulifloxacin	DMOK965	Urinary tract infection	GC08	Approved	[7]
Sparfloxacin	DMB4HCT	Bacterial infection	1A00-1C4Z	Approved	[2]
Trovafloxacin	DM6AN32	Acute gonococcal cervicitis		Approved	[2]

9 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD0914	DMM6G5D	Neisseria gonorrhoeae infection	1A7Z	Phase 3	[8]
BAY-35-3377	DMWYPZF	Otitis media	AA80-AB0Z	Phase 3	[9]
Pazufloxacin	DMHXTAQ	Conjunctivitis	9A60	Phase 3	[10]
Zabofloxacin	DMEY1F3	Pneumonia	CA40	Phase 3	[11]
Sitafloxacin	DMTV5XC	Escherichia coli infection	1A03	Phase 2/3	[12]
JNJ-32729463	DMQD1GN	Community-acquired pneumonia	CA40.Z	Phase 2	[13]
TNP-2092	DM8DZKI	Skin and skin-structure infection	1F28-1G0Z	Phase 2	[14]
VB 1953	DM0YWQ4	Acne vulgaris	ED80	Phase 2	[15]
WCK-771	DMVQARP	Bacterial infection	1A00-1C4Z	Phase 2	[16]

27 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Temafloxacin	DM3TON2	Bacterial infection	1A00-1C4Z	Withdrawn from market	[17]
OLAMUFLOXACIN MESILATE	DM0O2HP	Bacterial infection	1A00-1C4Z	Discontinued in Phase 3	[18]
99mTc-ciprofloxacin	DMSGY5M	Infectious disease	1A00-CA43.1	Discontinued in Phase 2	[19]
A-86719.1	DM7VSBH	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[20]
BAY-Y-3118	DMCZKG0	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[21]
Cadrofloxacin	DMHJ3SN	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[22]
CFC-222	DMHK8IM	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[23]
DANOFLOXACIN	DMF3E51	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[24]
DX-619	DMSTA5L	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[25]
FANDOFLOXACIN HYDROCHLORIDE	DM8UC0K	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[18]
Ro-23-9424	DM4YA63	Bacterial infection	1A00-1C4Z	Discontinued in Phase 2	[26]
AZD-5099	DMWKYV7	Infectious disease	1A00-CA43.1	Discontinued in Phase 1	[27]
Cetefloxacin	DM85SYL	Bacterial infection	1A00-1C4Z	Discontinued in Phase 1	[18]
DV-7751A	DMDC4BA	Bacterial infection	1A00-1C4Z	Discontinued in Phase 1	[28]
GSK945237	DM2AP64	Bacterial infection	1A00-1C4Z	Discontinued in Phase 1	[29]
PD-131112	DMVFGWM	Bacterial infection	1A00-1C4Z	Discontinued in Phase 1	[18]
A-70826	DM9X24J	Bacterial infection	1A00-1C4Z	Terminated	[31]
BMY-40062	DM2TF9P	Bacterial infection	1A00-1C4Z	Terminated	[32]
CBR-2092	DMJAGKY	Bacterial infection	1A00-1C4Z	Terminated	[33]
Clinafloxacin	DM6F8L5	Pneumonia	CA40	Terminated	[34]
CP-67015	DMWFI4A	Bacterial infection	1A00-1C4Z	Terminated	[2]
KB-5246	DM2LFYD	Bacterial infection	1A00-1C4Z	Terminated	[35]
MF-5137	DM72MQP	Staphylococcus infection	1B5Y	Terminated	[2]
PD-117596	DMN1A70	Bacterial infection	1A00-1C4Z	Terminated	[36]
Protosufloxacin	DM57YO8	Bacterial infection	1A00-1C4Z	Terminated	[2]
Ro-23-7777	DM7B2WH	Fungal infection	1F29-1F2F	Terminated	[2]
S-34109	DMPQIUH	Staphylococcus infection	1B5Y	Terminated	[37]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Viquidacin	DMS5LPF	Bacterial infection	1A00-1C4Z	Preclinical	[30]

2 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NSFQ-105	DMSLA8X	Discovery agent	N.A.	Investigative	[38]
PD-117558	DM3KAY5	Discovery agent	N.A.	Investigative	[39]

References

• [1] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [4] 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.
• [5] Nemonoxacin: first global approval. Drugs. 2014 Aug;74(12):1445-53.
• [6] 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.
• [7] Prulifloxacin: a new antibacterial fluoroquinolone. Expert Rev Anti Infect Ther. 2006 Feb;4(1):27-41.
• [8] 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.
• [9] Antibiotics in the clinical pipeline in 2013. J Antibiot (Tokyo). 2013 Oct;66(10):571-91.
• [10] Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition. Antimicrob Agents Chemother. 2001 Dec;45(12):3544-7.
• [11] DNA gyrase and topoisomerase IV are dual targets of zabofloxacin in Streptococcus pneumoniae.Int J Antimicrob Agents.2010 Jul;36(1):97-8.
• [12] Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumoniae. J Antimicrob Chemother. 2008 Jul;62(1):98-104.
• [13] Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2. Antimicrob Agents Chemother. 2011 Dec;55(12):5512-21.
• [14] Clinical pipeline report, company report or official report of TenNor Therapeutics.
• [15] Clinical pipeline report, company report or official report of Vyome Therapeutics.
• [16] Antistaphylococcal Activity of WCK 771, a Tricyclic Fluoroquinolone, in Animal Infection Models
• [17] Mechanisms and frequency of resistance to temafloxacin. Am J Med. 1991 Dec 30;91(6A):27S-30S.
• [18] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [19] 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.
• [20] Efficacy of ABT-719, a 2-pyridone antimicrobial, against enterococci, Escherichia coli, and Pseudomonas aeruginosa in experimental murine pyeloneph... J Antimicrob Chemother. 1996 Oct;38(4):641-53.
• [21] Bay Y 3118, a new quinolone derivative, rapidly eradicates Listeria monocytogenes from infected mice and L929 cells.
• [22] 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.
• [23] 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.
• [24] Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows. J Vet Pharmacol Ther. 1998 Jun;21(3):209-13.
• [25] 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.
• [26] Mode of action of the dual-action cephalosporin Ro 23-9424. Antimicrob Agents Chemother. 1989 Jul;33(7):1067-71.
• [27] Optimization of pyrrolamide topoisomerase II inhibitors toward identification of an antibacterial clinical candidate (AZD5099). J Med Chem. 2014 Jul 24;57(14):6060-82.
• [28] Antimicrobial activity of DV-7751a, a new fluoroquinolone.
• [29] Company report (gsk)
• [30] Selenophene-containing inhibitors of type IIA bacterial topoisomerases.J Med Chem.2011 May 12;54(9):3418-25.
• [31] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001978)
• [32] Relationships among antibacterial activity, inhibition of DNA gyrase, and intracellular accumulation of 11 fluoroquinolones. Antimicrob Agents Chemother. 1992 Dec;36(12):2622-7.
• [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.
• [34] DNA gyrase and topoisomerase IV are dual targets of clinafloxacin action in Streptococcus pneumoniae. Antimicrob Agents Chemother. 1998 Nov;42(11):2810-6.
• [35] Activity of KB-5246 against outer membrane mutants of Escherichia coli and Salmonella typhimurium.. Antimicrob Agents Chemother. 1990 July; 34(7): 1323-1325.
• [36] 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.
• [37] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007670)
• [38] 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.
• [39] 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.