Details of the Drug Combination

General Information of Drug Combination (ID: DCIKDQ8)

• Drug Combination Name: Ciprofloxacin XR + Ceftriaxone
• Indication: Gonococcal Infection; Status: Phase 1 [1]
• Component Drugs:
  Ciprofloxacin XR (DM2NLS9): Small molecular drug
  Ceftriaxone (DMCEW64): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ciprofloxacin XR

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[2]
Acute maxillary sinusitis	N.A.	Approved	[2]
Anthrax	1B97	Approved	[2]
Bacillary dysentery	1A02	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Chancroid	N.A.	Approved	[2]
Crohn disease	DD70	Approved	[2]
Cystitis	GC00	Approved	[2]
Fever	MG26	Approved	[2]
Gram-positive bacterial infection	1B74-1G40	Approved	[4]
Inflammation	1A00-CA43.1	Approved	[2]
Malignant otitis externa caused by Pseudomonas aeruginosa	N.A.	Approved	[2]
Prostatitis	N.A.	Approved	[5]
Staphylococcus aureus infection	N.A.	Approved	[2]
Traveler's diarrhea	ME05.1	Approved	[2]
Cystic fibrosis	CA25	Phase 2	[6]
Biliary cancer	2E92.7	Phase 1	[7]

Ciprofloxacin XR Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial DNA gyrase (Bact gyrase)	TTN6J5F	GYRA_STAAU; GYRB_STAAU	Modulator	[10]
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Inhibitor	[4]
Staphylococcus Topoisomerase IV (Stap-coc parC)	TTIXTO3	PARC_STAAS	Modulator	[10]
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[11]

Ciprofloxacin XR Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[12]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[13]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[14]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[15]

Ciprofloxacin XR Interacts with 22 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Expression	[16]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Decreases Expression	[16]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Expression	[16]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Increases Expression	[16]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[16]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[16]
POU domain, class 5, transcription factor 1 (POU5F1)	OTDHHN7O	PO5F1_HUMAN	Increases Expression	[16]
Homeobox protein NANOG (NANOG)	OTUEY1FM	NANOG_HUMAN	Increases Expression	[16]
Microphthalmia-associated transcription factor (MITF)	OT6XJCZH	MITF_HUMAN	Decreases Expression	[17]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[18]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Increases Expression	[19]
Stromelysin-1 (MMP3)	OTGBI74Z	MMP3_HUMAN	Increases Expression	[19]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[20]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Secretion	[21]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[22]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[23]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[23]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[20]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Decreases Expression	[24]
Aspartate aminotransferase, mitochondrial (GOT2)	OT6XBWN0	AATM_HUMAN	Increases ADR	[25]
DNA gyrase subunit A (gyrA)	OTFI7I9Z	GYRA_AERSA	Increases ADR	[25]
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2)	OTPGYWKC	NOD2_HUMAN	Decreases Response To Substance	[26]

Indication(s) of Ceftriaxone

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[8]
Bacteremia	1A73	Approved	[8]
Bacterial arthritis	N.A.	Approved	[8]
Bacterial infection	1A00-1C4Z	Approved	[9]
Chancroid	N.A.	Approved	[8]
Endometritis	N.A.	Approved	[8]
Escherichia coli meningitis	N.A.	Approved	[8]
Gonococcal infection of joint	N.A.	Approved	[8]
Meningococcal meningitis	N.A.	Approved	[8]
Pneumococcal meningitis	N.A.	Approved	[8]
Staphylococcal pneumonia	N.A.	Approved	[8]
Pelvic inflammatory disease	GA05	Investigative	[8]

Ceftriaxone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Modulator	[10]

Ceftriaxone Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[27]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[27]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[28]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[29]

Ceftriaxone Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Metabolism	[30]
Beta-lactamase (blaB)	DEYIEO5	AMPC_SERMA	Metabolism	[31]
Beta-lactamase (blaB)	DEBKS91	A0A1B1FBM9_ACIBA	Metabolism	[32]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Gonorrhea Male	DCA04R0	N. A.	Phase 2	[33]
Gonococcal Infection	DC4Z8NL	N. A.	Phase 1	[34]

References

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• [8] Ceftriaxone FDA Label
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• [13] Identification of the efflux transporter of the fluoroquinolone antibiotic ciprofloxacin in murine macrophages: studies with ciprofloxacin-resistant cells. Antimicrob Agents Chemother. 2009 Jun;53(6):2410-6.
• [14] Organic anion transporter 3 (oat3/slc22a8) interacts with carboxyfluoroquinolones, and deletion increases systemic exposure to ciprofloxacin. Mol Pharmacol. 2008 Jul;74(1):122-31.
• [15] Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol. 2010 Nov;70(5):645-55.
• [16] Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. Chem Biol Interact. 2016 Apr 25;250:1-11.
• [17] The role of MITF and Mcl-1 proteins in the antiproliferative and proapoptotic effect of ciprofloxacin in amelanotic melanoma cells: In silico and in vitro study. Toxicol In Vitro. 2020 Aug;66:104884. doi: 10.1016/j.tiv.2020.104884. Epub 2020 May 8.
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• [21] Quinolones as enhancers of camptothecin-induced cytotoxic and anti-topoisomerase I effects. Biochem Pharmacol. 2008 Mar 15;75(6):1272-81. doi: 10.1016/j.bcp.2007.11.014. Epub 2007 Dec 3.
• [22] Disturbance of cellular glucose transport by two prevalently used fluoroquinolone antibiotics ciprofloxacin and levofloxacin involves glucose transporter type 1. Toxicol Lett. 2009 Jan 30;184(2):81-4. doi: 10.1016/j.toxlet.2008.10.017. Epub 2008 Oct 28.
• [23] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [24] Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells. Rheumatology (Oxford). 2005 Dec;44(12):1514-7. doi: 10.1093/rheumatology/kei087. Epub 2005 Sep 7.
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• [26] NOD2/CARD15 gene variants are linked to failure of antibiotic treatment in perianal fistulating Crohn's disease. Am J Gastroenterol. 2008 May;103(5):1197-202. doi: 10.1111/j.1572-0241.2007.01741.x. Epub 2008 Mar 26.
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• [33] ClinicalTrials.gov (NCT05294588) Efficacy of Immunization With 4C-MenB in Preventing Experimental Urethral Infection With Neisseria Gonorrhoeae
• [34] ClinicalTrials.gov (NCT04870138) Experimental Human Infection With Neisseria Gonorrhoeae (LptA Trial)