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

General Information of Drug (ID: DMN9RPO)

• Drug Name: Nafcillin Drug Info
• Synonyms: Nafcilina; Nafcilline; Nafcillinum; Nallpen; Naphcillin; Naphthamidopenicillin; Unipen; NAFCILLIN SODIUM; Nafcillin sodium for injection; Nallpen In Plastic Container; Nafcilin-1; Nafcilina [INN-Spanish]; Nafcillin & VRC3375; Nafcillin (INN); Nafcillin [INN:BAN]; Nafcilline [INN-French]; Nafcillinum [INN-Latin]; Nafcillin, Monosodium Salt, Anhydrous; (2-Ethoxy-1-naphthyl)penicillin; (2-ethoxy-1-naphthalenyl)penicillin; (2S,5R,6R)-6-({[2-(ethyloxy)naphthalen-1-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-[(2-ethoxynaphthalene-1-carbonyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-{[(2-ethoxynaphthalen-1-yl)carbonyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-(2-ethoxy-1-naphthamido)penicillanic acid; 6-[(2-Ethoxy-naphthalene-1-carbonyl)-amino]-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid anion; 6beta-(2-ethoxynaphthalene-1-carboxamido)-2,2-dimethylpenam-3alpha-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Arthritis	FA20	Approved	[1]
Staphylococcal pneumonia		Approved	[2]
Staphylococcus aureus infection		Approved	[2]

• Therapeutic Class: Antibiotics
• Cross-matching ID:
  PubChem CID: 8982
  ChEBI ID: CHEMBL7447
  CAS Number: CAS 147-52-4
  TTD Drug ID: DMN9RPO
  VARIDT Drug ID: DR01384
  ACDINA Drug ID: D01266

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) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[15]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[4]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[16]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[18]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[19]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[20]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[21]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[18]

Drug(s) Affected By Nuclear receptor subfamily 1 group I member 2 (NR1I2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[5]
Vidarabine	DM0N85H	Hepatosplenic T-cell lymphoma		Approved	[5]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[23]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[24]
Etidronic acid	DM1XHYJ	Bone Paget disease		Approved	[5]
Tiaprofenic acid	DM23D7J	Osteoarthritis	FA00-FA05	Approved	[5]
Bromperidol	DM24XYQ	Schizophrenia	6A20	Approved	[5]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[26]

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 Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[5]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 062527.
• [2] Nafcillin FDA Label
• [3] Binding affinity for penicillin-binding protein 2a correlates with in vivo activity of beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus. J Infect Dis. 1990 Sep;162(3):705-10.
• [4] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [5] Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
• [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] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [16] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [17] Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
• [18] The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
• [19] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [20] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [21] FDA Drug Development and Drug Interactions
• [22] Induction of PXR-mediated metabolism by beta-carotene. Biochim Biophys Acta. 2005 May 30;1740(2):162-9. doi: 10.1016/j.bbadis.2004.11.013. Epub 2004 Dec 8.
• [23] Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol Appl Pharmacol. 2005 Dec 1;209(2):123-33. doi: 10.1016/j.taap.2005.03.015.
• [24] Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
• [25] Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9.
• [26] Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane X (PXR) receptor. Toxicol Lett. 2017 Jan 4;265:86-96.