Details of the Drug Combination

General Information of Drug Combination (ID: DCPY27I)

Drug Combination Name
Meglumine antimoniate Tofacitinib
Indication
Disease Entry Status REF
Cutaneous Leishmaniasis, American Phase 2 [1]
Component Drugs Meglumine antimoniate   DMINAG4 Tofacitinib   DMBS370
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Meglumine antimoniate
Disease Entry ICD 11 Status REF
Leishmania braziliensis infection 1F54.2 Approved [2]
Indication(s) of Tofacitinib
Disease Entry ICD 11 Status REF
Rheumatoid arthritis FA20 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [4]
Tofacitinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Janus kinase 3 (JAK-3) TTT7PJU JAK3_HUMAN Modulator [2]
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Tofacitinib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [7]
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Tofacitinib Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) OTPGHZB9 IFIT3_HUMAN Decreases Expression [6]
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Decreases Activity [5]
Cytochrome c oxidase subunit 1 (COX1) OTG3O9BN COX1_HUMAN Increases Expression [6]
2'-5'-oligoadenylate synthase 1 (OAS1) OT8ZLOCY OAS1_HUMAN Decreases Expression [6]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Decreases Expression [8]
Ubiquitin-like protein ISG15 (ISG15) OT53QQ7N ISG15_HUMAN Decreases Expression [6]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Expression [8]
Keratin, type I cytoskeletal 16 (KRT16) OTGA0EQN K1C16_HUMAN Decreases Expression [9]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) OTXOQDSG IFIT1_HUMAN Decreases Expression [10]
Interferon-induced transmembrane protein 1 (IFITM1) OTECO1G8 IFM1_HUMAN Decreases Expression [6]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Decreases Expression [8]
Interferon-induced GTP-binding protein Mx1 (MX1) OT6X8G5T MX1_HUMAN Decreases Expression [6]
Interferon-induced GTP-binding protein Mx2 (MX2) OT05NF37 MX2_HUMAN Decreases Expression [6]
Tyrosine-protein kinase JAK1 (JAK1) OT0X3D17 JAK1_HUMAN Decreases Activity [11]
2'-5'-oligoadenylate synthase 2 (OAS2) OT64CCTM OAS2_HUMAN Decreases Expression [6]
Succinate dehydrogenase flavoprotein subunit, mitochondrial (SDHA) OTOJ8QFF SDHA_HUMAN Increases Expression [6]
Interferon alpha-inducible protein 27, mitochondrial (IFI27) OTI2XGIT IFI27_HUMAN Decreases Expression [6]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Decreases Expression [6]
Signal transducer and activator of transcription 5B (STAT5B) OTZVPEBT STA5B_HUMAN Decreases Phosphorylation [12]
Interferon-induced 35 kDa protein (IFI35) OTV9RZ53 IN35_HUMAN Decreases Expression [6]
Interferon regulatory factor 9 (IRF9) OTK4MYQJ IRF9_HUMAN Decreases Expression [6]
AMP deaminase 2 (AMPD2) OTBS30JU AMPD2_HUMAN Decreases Expression [13]
Sonic hedgehog protein (SHH) OTOG2BXF SHH_HUMAN Increases Expression [6]
Secreted frizzled-related protein 5 (SFRP5) OTLCVVSH SFRP5_HUMAN Increases Expression [6]
Interferon-induced protein 44 (IFI44) OTOKSZVA IFI44_HUMAN Decreases Expression [6]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2) OTCA9WCM RSAD2_HUMAN Decreases Expression [6]
Interferon regulatory factor 7 (IRF7) OTC1A2PQ IRF7_HUMAN Decreases Expression [10]
Kelch-like protein 31 (KLHL31) OTXZVWDL KLH31_HUMAN Increases Expression [6]
Histone-lysine N-methyltransferase PRDM16 (PRDM16) OT0BGA27 PRD16_HUMAN Increases Expression [6]
Aldo-keto reductase family 1 member C1 (AKR1C1) OTQKR4CM AK1C1_HUMAN Increases Metabolism [14]
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⏷ Show the Full List of 30 DOT(s)

References

1 ClinicalTrials.gov (NCT06011343) Tofacitinib Associated With Meglumine Antimoniate in Cutaneous Leishmaniasis
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 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: 5677).
4 ClinicalTrials.gov (NCT04332042) TOFAcitinib in SARS-CoV2 Pneumonia. U.S. National Institutes of Health.
5 Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors. Eur J Pharmacol. 2015 Oct 15;765:188-97. doi: 10.1016/j.ejphar.2015.08.037. Epub 2015 Aug 20.
6 White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nat Cell Biol. 2015 Jan;17(1):57-67. doi: 10.1038/ncb3075. Epub 2014 Dec 8.
7 The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans. Drug Metab Dispos. 2014 Apr;42(4):759-73.
8 The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015 Jun;74(6):1311-6. doi: 10.1136/annrheumdis-2014-206028. Epub 2014 Nov 14.
9 Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study. J Allergy Clin Immunol. 2016 Apr;137(4):1079-1090. doi: 10.1016/j.jaci.2015.12.1318.
10 Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheum. 2012 Dec;64(12):3856-66. doi: 10.1002/art.37691.
11 JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res. 2014;2014:283617. doi: 10.1155/2014/283617. Epub 2014 May 5.
12 Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov. 2012 Jul;2(7):591-7. doi: 10.1158/2159-8290.CD-12-0028. Epub 2012 Jun 15.
13 Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes. Mod Rheumatol. 2015 Jul;25(4):522-7. doi: 10.3109/14397595.2014.995874. Epub 2015 Jan 13.
14 Elucidating the Mechanism of Tofacitinib Oxidative Decyanation. Drug Metab Lett. 2016;10(2):136-43. doi: 10.2174/1872312810666160427104954.