Details of the Drug

General Information of Drug (ID: DM5DSFZ)

• Drug Name: Rifampicin
• Synonyms: Rifadin; Rifadine; Rifagen; Rifaldazin; Rifaldazine; Rifaldin; Rifamor; Rifampicin; Rifampicin SV; Rifampicina; Rifampicina [INN-Spanish]; Rifampicine [French]; Rifampicinum; Rifampicinum [INN-Latin]; Rifamycin AMP; Rifaprodin; Rifcin; Rifinah; Rifobac; Rifoldin; Rifoldine; Riforal; Rimactan; Rimactane; Rimactazid; Rimactizid; Rimazid; Sinerdol; Tubocin; Archidyn; Arficin; Arzide; Benemicin; Dione 21-acetate; Doloresum; Eremfat; Fenampicin; L-5103 Lepetit; rifampin; 13292-46-1; Abrifam; Ba 41166/E; R/AMP; Rifa; Rifam

Indication

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Approved	[1]
Pulmonary tuberculosis	1B10.Z	Approved	[2]

• #Ro5 Violations (Lipinski): 3:
  Molecular Weight (mw); 822.9
  Logarithm of the Partition Coefficient (xlogp); 4.9
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 6
  Hydrogen Bond Acceptor Count (hbondacc); 15
• Chemical Identifiers:
  Formula: C43H58N4O12
  IUPAC Name: [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-[(E)-(4-methylpiperazin-1-yl)iminomethyl]-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(29),2,4,9,19,21,25,27-octaen-13-yl] acetate
  Canonical SMILES: CC1C=CC=C(C(=O)NC2=C(C(=C3C(=C2O)C(=C(C4=C3C(=O)C(O4)(OC=CC(C(C(C(C(C(C1O)C)O)C)OC(=O)C)C)OC)C)C)O)O)C=NN5CCN(CC5)C)C
  InChI: JQXXHWHPUNPDRT-WLSIYKJHSA-N
  InChIKey: 1S/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14+,22-13-,44-20+/t21-,23+,24+,25+,29-,34-,35+,39+,43-/m0/s1
• Cross-matching ID:
  PubChem CID: 135398735
  ChEBI ID: CHEBI:27470
  CAS Number: 13292-46-1
  DrugBank ID: DB01045
  INTEDE ID: DR1420
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Substrate	[4]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[5]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[6]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[8]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Substrate	[9]
Rifampicin monooxygenase (rox)	DE6PKFB	ROX_NOCFA	Substrate	[10]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[11]
28 kDa heat- and acid-stable phosphoprotein (PDAP1)	OTJSWMOD	HAP28_HUMAN	Gene/Protein Processing	[12]
3',5'-cyclic-AMP phosphodiesterase 4D (PDE4D)	OT1RWFV0	PDE4D_HUMAN	Gene/Protein Processing	[12]
5' exonuclease Apollo (DCLRE1B)	OT2LFW7A	DCR1B_HUMAN	Gene/Protein Processing	[12]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1)	OTQY6ZSF	HEM1_HUMAN	Gene/Protein Processing	[13]
ABC-type organic anion transporter ABCA8 (ABCA8)	OTCWLX6N	ABCA8_HUMAN	Gene/Protein Processing	[14]
ABI gene family member 3 (ABI3)	OTQTDSHP	ABI3_HUMAN	Gene/Protein Processing	[12]
Actin-related protein 10 (ACTR10)	OTRF3E58	ARP10_HUMAN	Gene/Protein Processing	[12]
Adenosine receptor A2a (ADORA2A)	OTVRBZ0I	AA2AR_HUMAN	Gene/Protein Processing	[12]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Gene/Protein Processing	[15]

References

• [1] Inhibitors can arrest the membrane activity of human islet amyloid polypeptide independently of amyloid formation. FEBS Lett. 2001 Oct 26;507(2):200-4.
• [2] Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children. Cochrane Database Syst Rev. 2022 Sep 6;9(9):CD013359.
• [3] Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist. J Clin Pharmacol. 2010 Aug;50(8):951-9.
• [4] Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice. Jpn J Pharmacol. 1995 Dec;69(4):325-34.
• [5] Xenobiotic-metabolizing cytochromes p450 in human white adipose tissue: expression and induction. Drug Metab Dispos. 2010 Apr;38(4):679-86.
• [6] 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.
• [7] Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers. Clin Pharmacol Ther. 2002 Nov;72(5):505-13.
• [8] Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos. 2003 Apr;31(4):421-31.
• [9] Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of induction by rifampin and ethnicity. Clin Pharmacol Ther. 2006 Jul;80(1):75-84.
• [10] Mechanism of rifampicin inactivation in Nocardia farcinica. PLoS One. 2016 Oct 5;11(10):e0162578.
• [11] Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 2005 Jan;115(1):177-86.
• [12] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [13] No activation of human pregnane X receptor by hyperforin-related phloroglucinols. J Pharmacol Exp Ther. 2014 Mar;348(3):393-400.
• [14] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [15] Rifampicin-induced injury in L02 cells is alleviated by 4-PBA via inhibition of the PERK-ATF4-CHOP pathway. Toxicol In Vitro. 2016 Oct;36:186-196. doi: 10.1016/j.tiv.2016.07.017. Epub 2016 Jul 26.