General Information of Drug Combination (ID: DCC02C4)

Drug Combination Name
Silver sulfadiazine Tacrolimus
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Silver sulfadiazine   DMVTHWQ Tacrolimus   DMZ7XNQ
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 2.62
Bliss Independence Score: 2.62
Loewe Additivity Score: 13.87
LHighest Single Agent (HSA) Score: 13.88

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Silver sulfadiazine
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [2]
Skin ulcer ME60.Z Approved [3]
Silver sulfadiazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial Dihydropteroate synthetase (Bact folP) TT4ILYC DHPS_ECOLI Binder [6]
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Indication(s) of Tacrolimus
Disease Entry ICD 11 Status REF
Graft-versus-host disease 4B24 Approved [4]
Hepatosplenic T-cell lymphoma N.A. Approved [4]
Kidney transplant rejection NE84 Approved [4]
Large granular lymphocytic leukemia 2A90.1 Approved [4]
Leukemia N.A. Approved [4]
Lupus nephritis 4A40.0Y Approved [4]
MALT lymphoma N.A. Approved [4]
Myeloproliferative neoplasm 2A20 Approved [4]
Nodal marginal zone lymphoma 2A85.0 Approved [4]
Organ transplant rejection NE84 Approved [5]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [4]
Recurrent adult burkitt lymphoma 2A85.6 Approved [4]
Small intestine lymphoma N.A. Approved [4]
Splenic marginal zone lymphoma N.A. Approved [4]
Testicular lymphoma N.A. Approved [4]
Ocular allergy 4A81 Phase 3 [5]
Classic Hodgkin lymphoma N.A. Investigative [4]
Tacrolimus Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Calcineurin (PPP3CA) TTA4LDE PP2BA_HUMAN Inhibitor [9]
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Tacrolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
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Tacrolimus Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [12]
NADPH-cytochrome P450 reductase (CPR) DE3N2FM NCPR_HUMAN Metabolism [13]
Ribosomal 23S RNA methyltransferase Erm (erm) DEW6V07 A0A5N1AHF6_CORAY Metabolism [14]
Ribosomal 23S RNA methyltransferase Erm (erm) DEA65D8 A0A381KDL2_CORJE Metabolism [14]
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Tacrolimus Interacts with 49 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Methylation [15]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Decreases Methylation [15]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Affects Response To Substance [16]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Response To Substance [17]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [18]
Cytochrome b-245 light chain (CYBA) OT16N9ZO CY24A_HUMAN Increases Expression [18]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Increases Expression [18]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [19]
Natural cytotoxicity triggering receptor 3 (NCR3) OT20M764 NCTR3_HUMAN Increases Expression [20]
Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) OTCYYCAC HGS_HUMAN Increases Expression [8]
Rho guanine nucleotide exchange factor 11 (ARHGEF11) OTDOMEH6 ARHGB_HUMAN Increases Expression [8]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [21]
Actin-related protein 2/3 complex subunit 5 (ARPC5) OTFNMMDL ARPC5_HUMAN Increases Expression [8]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [21]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Increases Expression [7]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [22]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [23]
Interferon gamma (IFNG) OTXG9JM7 IFNG_HUMAN Decreases Expression [24]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [25]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Increases Expression [26]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [26]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Decreases Expression [24]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [24]
Interleukin-5 (IL5) OTAFPSCO IL5_HUMAN Decreases Expression [27]
Interleukin-3 (IL3) OT0CQ35N IL3_HUMAN Decreases Expression [24]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [28]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Decreases Expression [7]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [27]
Ras-related protein Rab-4A (RAB4A) OT7BL9WW RAB4A_HUMAN Increases Expression [8]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Degradation [23]
T-lymphocyte activation antigen CD80 (CD80) OTJBLUQE CD80_HUMAN Decreases Expression [29]
T-lymphocyte activation antigen CD86 (CD86) OTJCSBPC CD86_HUMAN Decreases Expression [29]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [30]
Troponin T, cardiac muscle (TNNT2) OT80NN7R TNNT2_HUMAN Increases Expression [31]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Decreases Secretion [32]
Glycogen synthase kinase-3 alpha (GSK3A) OT0F6DWV GSK3A_HUMAN Increases Phosphorylation [7]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Phosphorylation [7]
Eotaxin (CCL11) OT3BIFPK CCL11_HUMAN Decreases Expression [27]
C-C chemokine receptor type 3 (CCR3) OT6GBUFA CCR3_HUMAN Decreases Expression [27]
LIM domain kinase 1 (LIMK1) OTFZ8MZ0 LIMK1_HUMAN Increases Expression [8]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Decreases Expression [24]
Neutrophil gelatinase-associated lipocalin (LCN2) OTSB42BR NGAL_HUMAN Increases Expression [26]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [30]
Lethal(2) giant larvae protein homolog 1 (LLGL1) OTAIQSXZ L2GL1_HUMAN Increases Expression [8]
Calcineurin subunit B type 1 (PPP3R1) OTGQNFJQ CANB1_HUMAN Increases ADR [33]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Response To Substance [34]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Response To Substance [34]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Affects Response To Substance [16]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Decreases Methylation [15]
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⏷ Show the Full List of 49 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4126).
3 Silver sulfadiazine FDA Label
4 Tacrolimus FDA Label
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6784).
6 Comparative evaluation of transdermal formulations of norfloxacin with silver sulfadiazine cream, USP, for burn wound healing property. J Burns Wounds. 2006 Jun 7;5:e4.
7 GSK3, snail, and adhesion molecule regulation by cyclosporine A in renal tubular cells. Toxicol Sci. 2012 Jun;127(2):425-37. doi: 10.1093/toxsci/kfs108. Epub 2012 Mar 12.
8 Calcineurin is an important factor involved in glucose uptake in human adipocytes. Mol Cell Biochem. 2018 Aug;445(1-2):157-168. doi: 10.1007/s11010-017-3261-0. Epub 2018 Jan 27.
9 Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20.
10 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
11 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
12 Tacrolimus pharmacokinetics and pharmacogenetics: influence of adenosine triphosphate-binding cassette B1 (ABCB1) and cytochrome (CYP) 3A polymorphisms. Fundam Clin Pharmacol. 2007 Aug;21(4):427-35.
13 Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
14 High frequency of macrolide resistance mechanisms in clinical isolates of Corynebacterium species. Microb Drug Resist. 2010 Dec;16(4):273-7.
15 Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clin Chem. 2005 Aug;51(8):1374-81.
16 Single-nucleotide polymorphisms in P450 oxidoreductase and peroxisome proliferator-activated receptor- are associated with the development of new-onset diabetes after transplantation in kidney transplant recipients treated with tacrolimus. Pharmacogenet Genomics. 2013 Dec;23(12):649-57. doi: 10.1097/FPC.0000000000000001.
17 Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene. Transplantation. 2002 Aug 27;74(4):571-2. doi: 10.1097/00007890-200208270-00024.
18 Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. J Cardiovasc Pharmacol. 2002 Oct;40(4):625-31.
19 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
20 Mycophenolic acid inhibits natural killer cell proliferation and cytotoxic function: a possible disadvantage of including mycophenolate mofetil in the graft-versus-host disease prophylaxis regimen. Biol Blood Marrow Transplant. 2011 Feb;17(2):205-13. doi: 10.1016/j.bbmt.2010.08.014. Epub 2010 Aug 22.
21 CyclinB2 and BIRC5 genes as surrogate biomarkers for neurite outgrowth in SH-SY5Y subclonal cells. Neuropharmacology. 2006 Jun;50(8):1041-7. doi: 10.1016/j.neuropharm.2006.02.004. Epub 2006 Mar 30.
22 Effects of immunosuppressive drugs on in vitro neogenesis of human islets: mycophenolate mofetil inhibits the proliferation of ductal cells. Am J Transplant. 2007 Apr;7(4):1021-6. doi: 10.1111/j.1600-6143.2006.01728.x.
23 FK506 inhibits tumour necrosis factor-alpha secretion in human keratinocytes via regulation of nuclear factor-kappaB. Br J Dermatol. 2005 Oct;153(4):725-32. doi: 10.1111/j.1365-2133.2005.06779.x.
24 Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids). Int Immunopharmacol. 2001 Jun;1(6):1219-26. doi: 10.1016/s1567-5769(01)00059-5.
25 Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.
26 Tacrolimus-induced nephrotoxicity in mice is associated with microRNA deregulation. Arch Toxicol. 2018 Apr;92(4):1539-1550. doi: 10.1007/s00204-018-2158-3. Epub 2018 Jan 23.
27 Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis. Br J Dermatol. 2005 Jun;152(6):1173-81. doi: 10.1111/j.1365-2133.2005.06474.x.
28 A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
29 Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no Langerhans cell apoptosis in patients with atopic dermatitis. J Allergy Clin Immunol. 2004 Jul;114(1):137-43. doi: 10.1016/j.jaci.2004.03.021.
30 Immunosuppressive calcineurin inhibitor cyclosporine A?induces proapoptotic endoplasmic reticulum stress in renal tubular cells. J Biol Chem. 2022 Mar;298(3):101589. doi: 10.1016/j.jbc.2022.101589. Epub 2022 Jan 14.
31 Multicenter prospective investigation on cardiovascular adverse effects of tacrolimus in kidney transplantations. Cardiovasc Drugs Ther. 2003 Mar;17(2):141-9. doi: 10.1023/a:1025339819051.
32 Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis. J Allergy Clin Immunol. 2001 Nov;108(5):839-46. doi: 10.1067/mai.2001.118796.
33 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.
34 Hydrogen peroxide mediates FK506-induced cytotoxicity in renal cells. Kidney Int. 2004 Jan;65(1):139-47. doi: 10.1111/j.1523-1755.2004.00380.x.