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

General Information of Drug (ID: DMUTL7O)

• Drug Name: Cloxacillin Drug Info
• Synonyms: Chloroxacillin; Clossacillina; Cloxacilina; Cloxacilline; Cloxacillinum; MCIPC; Orbenin; Syntarpen; Tegopen; Clossacillina [DCIT]; Cloxacillin sodium; Methocillin S; BRL 1621; Cloxacilina [INN-Spanish]; Cloxacillin (INN); Cloxacillin [INN:BAN]; Cloxacilline [INN-French]; Cloxacillinum [INN-Latin]; Cloxapen (TN); Cloxapen (sodium monohydrate); Methylchlorphenylisoxazoryl-penicillin; Novo-Cloxin; Nu-Cloxi; Orbenin (TN); Tegopen (sodium monohydrate); BRL-1621 (sodium monohydrate); P-25 (sodium monohydrate); [3-(O-CHLOROPHENYL)-5-METHYL-4-ISOXAZOLYL]PENICILLIN; (2S,5R,6R)-6-({[3-(2-chlorophenyl)-5-methylisoxazol-4-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-[[3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (3-(o-Chlorophenyl)-5-methyl-4-isoxazolyl)penicillin; 6-(((3-(2-Chlorophenyl)-5-methyl-4-isoxazolyl)carbonyl)amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid; 6-(3-(o-Chlorophenyl)-5-methyl-4-isoxazolecarboxamido)penicillanic acid

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]
Staphylococcal pneumonia		Approved	[2]
Staphylococcus aureus infection		Approved	[2]
Sinusitis	CA0A.Z	Investigative	[2]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 6098
  ChEBI ID: CHEBI:49566
  CAS Number: CAS 61-72-3
  TTD Drug ID: DMUTL7O
  VARIDT Drug ID: DR00529
  ACDINA Drug ID: D00960

Molecule-Related Drug Atlas

Drug(s) Targeting Bacterial Penicillin binding protein (Bact PBP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[6]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[7]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[8]
Ticarcillin	DM4ME02	Aspiration pneumonia		Approved	[9]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[10]
Meropenem	DM62UHC	Bacterial infection	1A00-1C4Z	Approved	[8]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[11]
Clofarabine	DMCVJ86	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[13]
Carbenicillin	DMLEDNK	Infection of the upper and lower urinary tract	GC08	Approved	[14]

Drug(s) Affected By Bile salt export pump (ABCB11)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[15]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[16]
Glipizide	DMZA5PQ	Diabetic complication	5A2Y	Approved	[16]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[17]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[15]
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[16]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[18]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[15]
Drospirenone	DM1A9W3	Acne vulgaris	ED80	Approved	[19]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[15]

Drug(s) Affected By Caspase-3 (CASP3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[20]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[22]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[23]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[26]
Mannitol	DMSCDY9	Bronchiectasis	CA24	Approved	[27]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[28]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[4]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[5]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 061454.
• [2] Cloxacillin FDA Label
• [3] Development of a receptor-based microplate assay for the detection of beta-lactam antibiotics in different food matrices. Anal Chim Acta. 2007 Mar 14;586(1-2):296-303.
• [4] Potential cholestatic activity of various therapeutic agents assessed by bile canalicular membrane vesicles isolated from rats and humans. Drug Metab Pharmacokinet. 2003;18(1):16-22.
• [5] Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics. Toxicol In Vitro. 2019 Aug;58:51-59. doi: 10.1016/j.tiv.2019.03.015. Epub 2019 Mar 12.
• [6] Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci. Antimicrob Agents Chemother. 2002 May;46(5):1273-80.
• [7] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Activities of antibiotics against methicillin-resistant Staphylococcus aureus with particular reference to synergetic effect between ticarcillin and fosfomycin on penicillinase non-producing methicillin-resistant S. aureus. Jpn J Antibiot. 1993 Jun;46(6):421-7.
• [10] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [11] Penicillin-binding protein sensitive to cephalexin in sporulation of Bacillus cereus. Microbiol Res. 1997 Sep;152(3):227-32.
• [12] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [13] Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics. J Med Microbiol. 2004 Mar;53(Pt 3):213-21.
• [14] Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J Antimicrob Chemother. 1990 Apr;25(4):513-23.
• [15] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [16] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [17] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [18] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [19] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [20] Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesia. Acta Anaesthesiol Scand. 2009 Oct;53(9):1192-9. doi: 10.1111/j.1399-6576.2009.02036.x. Epub 2009 Jun 30.
• [21] [Mechanisms underlying the effect of arsenic trioxide on proliferation inhibition and apoptosis induction in myeloma cell line u266]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Oct;15(5):982-5.
• [22] Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPAR-dependent pathway. Oncotarget. 2016 Mar 1;7(9):10345-62. doi: 10.18632/oncotarget.7213.
• [23] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [24] Comparison of burst of reactive oxygen species and activation of caspase-3 in apoptosis of K562 and HL-60 cells induced by docetaxel. Cancer Lett. 2004 Oct 8;214(1):103-13. doi: 10.1016/j.canlet.2004.03.047.
• [25] Induction of mitochondrial manganese superoxide dismutase confers resistance to apoptosis in acute myeloblastic leukaemia cells exposed to etoposide. Br J Haematol. 2000 Mar;108(3):574-81. doi: 10.1046/j.1365-2141.2000.01852.x.
• [26] Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro. Tumour Biol. 2010 Dec;31(6):613-22. doi: 10.1007/s13277-010-0077-x. Epub 2010 Jul 11.
• [27] Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis. J Cell Physiol. 2000 Jan;182(1):24-32. doi: 10.1002/(SICI)1097-4652(200001)182:1<24::AID-JCP3>3.0.CO;2-6.
• [28] mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment with carboplatin and doxorubicin. Biol Chem. 2004 Nov;385(11):1099-103. doi: 10.1515/BC.2004.143.
• [29] Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.