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

General Information of Drug (ID: DMTV5XC)

• Drug Name: Sitafloxacin Drug Info
• Synonyms: Sitafloxacin; Gracevit; Sitafloxacin Sesquihydrate; UNII-3GJC60U4Q8; Sitafloxacin isomer II; DU-6859a; C19H18ClF2N3O3; 3GJC60U4Q8; 7-((S)-7-AMINO-5-AZASPIRO[2.4]HEPTAN-5-YL)-8-CHLORO-6-FLUORO-1-((1R,2S)-2-FLUOROCYCLOPROPYL)-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID; STFX; 7-[(7S)-7-amino-5-azaspiro[2.4]heptan-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-quinoline-3-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Escherichia coli infection	1A03	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 461399
  ChEBI ID: CHEBI:4304
  CAS Number: CAS 127254-12-0
  TTD Drug ID: DMTV5XC
  VARIDT Drug ID: DR01687

Molecule-Related Drug Atlas

Drug(s) Targeting Bacterial DNA gyrase (Bact gyrase)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Grepafloxacin	DMGLX0T	Chronic bronchitis	CA20.1	Approved	[5]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[6]
Levofloxacin	DMS60RB	Acute maxillary sinusitis		Approved	[6]
Gatifloxacin	DMSL679	Acute gonococcal cervicitis		Approved	[6]
Norfloxacin	DMIZ6W2	Acute gonococcal cervicitis		Approved	[6]
Ozenoxacin	DM6KZMG	Impetigo	1B72	Approved	[7]
Sparfloxacin	DMB4HCT	Bacterial infection	1A00-1C4Z	Approved	[6]
Gemifloxacin	DMHT34O	Bacterial infection	1A00-1C4Z	Approved	[6]
Besifloxacin	DMPHXMI	Ocular inflammation	9C61.24	Approved	[8]
Finafloxacin	DMZEONG	Urinary tract infection	GC08	Approved	[9]

Drug(s) Targeting Bacterial DNA topoisomerase 4A (Bact parC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Prulifloxacin	DMOK965	Urinary tract infection	GC08	Approved	[10]
Pazufloxacin	DMHXTAQ	Conjunctivitis	9A60	Phase 3	[11]
VB 1953	DM0YWQ4	Acne vulgaris	ED80	Phase 2	[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]
A-62824	DMJ6IMZ	Discovery agent	N.A.	Investigative	[15]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[3]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[16]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[18]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial DNA gyrase (Bact gyrase)	TTN6J5F	GYRA_STAAU; GYRB_STAAU	Inhibitor	[2]
Bacterial DNA topoisomerase 4A (Bact parC)	TTFK8YB	PARC_ECOLI	Inhibitor	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
UDP-glucuronosyltransferase 1A1	OTH1C8OJ	UD11_HUMAN	Biotransformations	[4]
UDP-glucuronosyltransferase 1A3	OTUEOER3	UD13_HUMAN	Biotransformations	[4]
UDP-glucuronosyltransferase 1A7	OTY4JJ32	UD17_HUMAN	Biotransformations	[4]
UDP-glucuronosyltransferase 1A9	OTPCHAFX	UD19_HUMAN	Biotransformations	[4]

References

• [1] ClinicalTrials.gov (NCT02537847) Sitafloxacin and Ertapenem Treatment for Acute Pyelonephritis Caused by Escherichia Coli (SETAP). U.S. National Institutes of Health.
• [2] 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.
• [3] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [4] Acyl glucuronidation of fluoroquinolone antibiotics by the UDP-glucuronosyltransferase 1A subfamily in human liver microsomes. Drug Metab Dispos. 2005 Jun;33(6):803-11. doi: 10.1124/dmd.104.003178. Epub 2005 Mar 15.
• [5] 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.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] 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.
• [8] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [9] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [10] Prulifloxacin: a new antibacterial fluoroquinolone. Expert Rev Anti Infect Ther. 2006 Feb;4(1):27-41.
• [11] Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition. Antimicrob Agents Chemother. 2001 Dec;45(12):3544-7.
• [12] Clinical pipeline report, company report or official report of Vyome Therapeutics.
• [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] Isothiazoloquinolones containing functionalized aromatic hydrocarbons at the 7-position: synthesis and in vitro activity of a series of potent anti... Bioorg Med Chem Lett. 2006 Mar 1;16(5):1272-6.
• [16] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [17] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [18] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [19] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [20] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [21] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.