Details of the Drug

General Information of Drug (ID: DMWVCF3)

• Drug Name: Fusidic acid
• Synonyms: FUCIDIN; Fucidate; Fucithalmic; Fusidate; Fusidine; Ramycin; Diethanolamine fusidate; Fucidate Sodium; Fucidic acid; Fucidin acid; Fuci (TN); Fucibet (TN); Fucicort (TN); Fucidin (TN); Fucidin Cream 2%; Fucidine (TN); Fucithalmic (TN); Fucizon (TN); Fudic (TN); Fusiderm (TN); Fusidin (TN); SQ 16,603; Fusidic acid (USAN/INN); C.A.S. 62,602; (2Z)-2-[(17Z)-16beta-acetoxy-3alpha,11alpha-dihydroxy-4alpha,8alpha,10,14beta-tetramethyl-5alpha,9beta,13alpha-gonan-17-ylidene]-6-methylhept-5-enoic acid; (2Z)-2-[(3R,4S,5S,8S,9S,10S,11R,13R,14S,16S)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoic acid; (2Z)-2-[(3alpha,4alpha,5alpha,8alpha,9beta,11alpha,13alpha,14beta,16beta,17Z)-16-(acetyloxy)-3,11-dihydroxy-4,8,10,14-tetramethylgonan-17-ylidene]-6-methylhept-5-enoic acid; 16-(Acetyloxy)-3,11-dihydroxy-29-nordammara-17(20),24-dien-21-oic acid; 3.alpha.,11.alpha.,16.beta.-Trihydroxy-29-nor-8.alpha.,9.beta.,13.alpha.,14.beta.-dammara-17(20),24-dien-21-oic acid 16-acetate

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]
MRSA infection	1D01.0Y	Phase 3	[2]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 516.7
  Topological Polar Surface Area (xlogp); 5.5
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Bioavailability: 91% of drug becomes completely available to its intended biological destination(s) [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 5 - 6 hours [5]
• Chemical Identifiers:
  Formula: C31H48O6
  IUPAC Name: (2Z)-2-[(3R,4S,5S,8S,9S,10S,11R,13R,14S,16S)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoic acid
  Canonical SMILES: C[C@H]1[C@@H]2CC[C@]3([C@H]([C@]2(CC[C@H]1O)C)[C@@H](C[C@@H]\\4[C@@]3(C[C@@H](/C4=C(/CCC=C(C)C)\\C(=O)O)OC(=O)C)C)O)C
  InChI: InChI=1S/C31H48O6/c1-17(2)9-8-10-20(28(35)36)26-22-15-24(34)27-29(5)13-12-23(33)18(3)21(29)11-14-30(27,6)31(22,7)16-25(26)37-19(4)32/h9,18,21-25,27,33-34H,8,10-16H2,1-7H3,(H,35,36)/b26-20-/t18-,21-,22-,23+,24+,25-,27-,29-,30-,31-/m0/s1
  InChIKey: IECPWNUMDGFDKC-MZJAQBGESA-N
• Cross-matching ID:
  PubChem CID: 3000226
  ChEBI ID: CHEBI:29013
  CAS Number: 6990-06-3
  DrugBank ID: DB02703
  TTD ID: D0X7XG
  INTEDE ID: DR0758

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Streptococcus Elongation factor G (Stre-coc fusA)	TT6HP1T	EFG_STRZJ	Inhibitor	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[8]

References

• [1] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [2] Application of pharmacokinetic-pharmacodynamic modeling and the justification of a novel fusidic acid dosing regimen: raising Lazarus from the dead. Clin Infect Dis. 2011 Jun;52 Suppl 7:S513-9.
• [3] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [4] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Genetic determinants of resistance to fusidic acid among clinical bacteremia isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 2009 May;53(5):2059-65.
• [7] The potent mechanism-based inactivation of CYP2D6 and CYP3A4 with fusidic acid in in vivo bioaccumulation. Xenobiotica. 2018 Oct;48(10):999-1005.
• [8] Fusidic acid inhibits hepatic transporters and metabolic enzymes: potential cause of clinical drug-drug interaction observed with statin coadministration. Antimicrob Agents Chemother. 2016 Sep 23;60(10):5986-94.
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• [12] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
• [13] Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
• [14] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
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• [17] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [18] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
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• [20] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [21] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [22] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [23] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [24] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [25] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [26] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [27] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [28] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
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