General Information of Drug Combination (ID: DC5O6NC)

Drug Combination Name
Isoniazid Rifapentine
Indication
Disease Entry Status REF
Tuberculosis, Pulmonary Phase 3 [1]
Component Drugs Isoniazid   DM5JVS3 Rifapentine   DMCHV4I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Isoniazid
Disease Entry ICD 11 Status REF
Latent tuberculosis infection N.A. Approved [2]
Pulmonary tuberculosis 1B10.Z Approved [2]
Tuberculosis 1B10-1B1Z Approved [3]
Isoniazid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Fatty acid synthetase I (Bact inhA) TTVTX4N INHA_MYCTU Inhibitor [7]
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Isoniazid Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [8]
Catalase-peroxidase (katG) DEAGY5M KATG_SYNE7 Metabolism [9]
Arylamine N-acetyltransferase (NAT) DEXCQTM A0A3P8LE58_TSUPA Metabolism [10]
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Isoniazid Interacts with 59 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Expression [11]
N-alpha-acetyltransferase 20 (NAA20) OTJB0VA6 NAA20_HUMAN Increases ADR [12]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [13]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [14]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [14]
Protein DEPP1 (DEPP1) OTB36PHJ DEPP1_HUMAN Increases Expression [14]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Increases Expression [6]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Secretion [6]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Increases Secretion [6]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Increases Secretion [6]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Secretion [6]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [6]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Secretion [6]
Interleukin-12 subunit alpha (IL12A) OTDQT8GI IL12A_HUMAN Increases Secretion [6]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Increases Secretion [6]
Interleukin-17A (IL17A) OTY72FT2 IL17_HUMAN Increases Secretion [6]
Sulfiredoxin-1 (SRXN1) OTYDBO4L SRXN1_HUMAN Increases Expression [6]
Gamma-butyrobetaine dioxygenase (BBOX1) OTKEX4RK BODG_HUMAN Increases Expression [15]
Alpha-fetoprotein (AFP) OT9GG3ZI FETA_HUMAN Decreases Expression [15]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1) OTTO6ZP4 AT1B1_HUMAN Increases Expression [15]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Increases Expression [15]
Osteopontin (SPP1) OTJGC23Y OSTP_HUMAN Decreases Expression [15]
Mucin-1 (MUC1) OTHQI7IY MUC1_HUMAN Increases Expression [15]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Decreases Expression [15]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Decreases Expression [15]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Decreases Expression [15]
Claudin-2 (CLDN2) OTRF3D6Y CLD2_HUMAN Increases Expression [15]
Large neutral amino acids transporter small subunit 1 (SLC7A5) OT2WPVXD LAT1_HUMAN Decreases Expression [15]
Tribbles homolog 3 (TRIB3) OTG5OS7X TRIB3_HUMAN Increases Expression [15]
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) OTKOZRZP PLOD2_HUMAN Increases Expression [16]
Transmembrane protease serine 2 (TMPRSS2) OTN44YQ5 TMPS2_HUMAN Affects Expression [17]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Increases Expression [18]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [18]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [19]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Increases Expression [18]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Activity [20]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [20]
Glucose-6-phosphate 1-dehydrogenase (G6PD) OT300SMK G6PD_HUMAN Decreases Activity [20]
5-aminolevulinate synthase, non-specific, mitochondrial (ALAS1) OTQY6ZSF HEM1_HUMAN Increases Expression [21]
Ferrochelatase, mitochondrial (FECH) OTDWEI6C HEMH_HUMAN Decreases Expression [21]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [11]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [11]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [18]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [22]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [20]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [20]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [11]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [18]
Nuclear respiratory factor 1 (NRF1) OTOXWNV8 NRF1_HUMAN Decreases Expression [23]
Natural cytotoxicity triggering receptor 3 ligand 1 (NCR3LG1) OT15YWU7 NR3L1_HUMAN Increases Expression [24]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [18]
NAD-dependent protein deacetylase sirtuin-1 (SIRT1) OTAYZMOY SIR1_HUMAN Decreases Expression [23]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [17]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Decreases Expression [23]
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Decreases Acetylation [25]
Eosinophil peroxidase (EPX) OTFNDFOK PERE_HUMAN Increases Oxidation [26]
Myeloperoxidase (MPO) OTOOXLIN PERM_HUMAN Increases Oxidation [27]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Response To Substance [28]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Decreases Response To Substance [29]
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⏷ Show the Full List of 59 DOT(s)
Indication(s) of Rifapentine
Disease Entry ICD 11 Status REF
Pulmonary tuberculosis 1B10.Z Approved [4]
Tuberculosis 1B10-1B1Z Approved [3]
Macular degeneration 9B78.3 Investigative [5]
Rifapentine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA-directed RNA polymerase (RNAP) TTHKJLN NOUNIPROTAC Binder [30]
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Rifapentine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [31]
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Rifapentine Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [32]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [33]
Arylacetamide deacetylase (AADAC) OT8VACT2 AAAD_HUMAN Decreases Acetylation [34]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
HIV Infections DCRMHA9 N. A. Phase 1 [35]
Tuberculosis DCW9U5X N. A. Phase 1 [36]
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References

1 ClinicalTrials.gov (NCT05454345) Sitafloxacin-containing Regimens for Shortening Tuberculosis Treatment
2 Isoniazid FDA Label
3 Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
4 Rifapentine FDA Label
5 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
6 Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
7 Diversity in enoyl-acyl carrier protein reductases. Cell Mol Life Sci. 2009 May;66(9):1507-17.
8 Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93.
9 Crystal structure of the catalase-peroxidase KatG W78F mutant from Synechococcus elongatus PCC7942 in complex with the antitubercular pro-drug isoniazid. FEBS Lett. 2015 Jan 2;589(1):131-7.
10 The actinobacterium Tsukamurella paurometabola has a functionally divergent arylamine N-acetyltransferase (NAT) homolog. World J Microbiol Biotechnol. 2019 Oct 31;35(11):174.
11 Quercetin protected against isoniazide-induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway. J Biochem Mol Toxicol. 2019 Sep;33(9):e22369. doi: 10.1002/jbt.22369. Epub 2019 Jul 23.
12 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
13 Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007.
14 Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
15 Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq. Arch Toxicol. 2018 Aug;92(8):2517-2531.
16 Identification of differentially expressed genes in hepatic HepG2 cells treated with acetaminophen using suppression subtractive hybridization. Biol Pharm Bull. 2005 Jul;28(7):1148-53. doi: 10.1248/bpb.28.1148.
17 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
18 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
19 Auto-oxidation of Isoniazid Leads to Isonicotinic-Lysine Adducts on Human Serum Albumin. Chem Res Toxicol. 2015 Jan 20;28(1):51-8. doi: 10.1021/tx500285k. Epub 2014 Dec 9.
20 Isoniazid-induced apoptosis in HepG2 cells: generation of oxidative stress and Bcl-2 down-regulation. Toxicol Mech Methods. 2010 Jun;20(5):242-51. doi: 10.3109/15376511003793325.
21 The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis. Toxicol Sci. 2019 Mar 1;168(1):209-224. doi: 10.1093/toxsci/kfy294.
22 Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes. Toxicol Appl Pharmacol. 2013 Dec 15;273(3):435-41. doi: 10.1016/j.taap.2013.10.005. Epub 2013 Oct 12.
23 AMPK activator acadesine fails to alleviate isoniazid-caused mitochondrial instability in HepG2 cells. J Appl Toxicol. 2017 Oct;37(10):1219-1224. doi: 10.1002/jat.3483. Epub 2017 May 29.
24 Enhanced activation of human NK cells by drug-exposed hepatocytes. Arch Toxicol. 2020 Feb;94(2):439-448. doi: 10.1007/s00204-020-02668-8. Epub 2020 Feb 14.
25 Effects of N-acetyltransferase 2 (NAT2), CYP2E1 and Glutathione-S-transferase (GST) genotypes on the serum concentrations of isoniazid and metabolites in tuberculosis patients. J Toxicol Sci. 2008 May;33(2):187-95. doi: 10.2131/jts.33.187.
26 Eosinophil peroxidase oxidizes isoniazid to form the active metabolite against M. tuberculosis, isoniazid-NAD(). Chem Biol Interact. 2019 May 25;305:48-53. doi: 10.1016/j.cbi.2019.03.019. Epub 2019 Mar 25.
27 Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD(+) adduct formation: A comparison of the reactivity of isoniazid with its known human metabolites. Biochem Pharmacol. 2016 Apr 15;106:46-55. doi: 10.1016/j.bcp.2016.02.003. Epub 2016 Feb 9.
28 Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation. Drug Metab Dispos. 2011 Aug;39(8):1388-95. doi: 10.1124/dmd.110.037077. Epub 2011 May 3.
29 Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury. Arch Toxicol. 2018 Jan;92(1):383-399. doi: 10.1007/s00204-017-2036-4. Epub 2017 Jul 31.
30 Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1998 Jul;42(7):1853-7.
31 Inhibitory potential of twenty five anti-tuberculosis drugs on CYP activities in human liver microsomes. Biol Pharm Bull. 2015;38(9):1425-9.
32 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
33 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
34 Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine. Biochem Pharmacol. 2011 Dec 1;82(11):1747-56.
35 ClinicalTrials.gov (NCT00057122) Tuberculosis Prevention for HIV Infected Adults
36 ClinicalTrials.gov (NCT01404312) Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)