Details of the Drug Combination

General Information of Drug Combination (ID: DCKXEXF)

Drug Combination Name
Deferoxamine Hydroxyurea
Indication
Disease Entry Status REF
Iron Overload Phase 2 [1]
Component Drugs Deferoxamine   DMG0C81 Hydroxyurea   DMOQVU9
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Deferoxamine
Disease Entry ICD 11 Status REF
Acute iron or aluminum toxicity FB83.20 Approved [2]
Subarachnoid hemorrhage 8B01 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 1/2 [4]
Indication(s) of Hydroxyurea
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [5]
Desmoid tumour 2F7C Approved [6]
Fibromatosis N.A. Approved [6]
Head and neck cancer 2D42 Approved [6]
Melanoma 2C30 Approved [6]
Pulmonary hypertension BB01 Approved [6]
Sickle-cell anaemia 3A51 Approved [6]
Hydroxyurea Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ribonucleoside-diphosphate reductase M2 (RRM2) TTBWDI0 RIR2_HUMAN Modulator [12]
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Hydroxyurea Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [14]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [14]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [14]
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Hydroxyurea Interacts with 113 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Increases Uptake [14]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Uptake [14]
Solute carrier organic anion transporter family member 1A2 (SLCO1A2) OTO70C5O SO1A2_HUMAN Increases Uptake [14]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Increases ADR [15]
Serine/threonine-protein kinase Sgk1 (SGK1) OT301T1U SGK1_HUMAN Increases Expression [7]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [7]
TP53-regulated inhibitor of apoptosis 1 (TRIAP1) OTEAUJXN TRIA1_HUMAN Increases Expression [7]
Heat shock cognate 71 kDa protein (HSPA8) OTJI2RCI HSP7C_HUMAN Increases Expression [7]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Increases Expression [7]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Increases Expression [7]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [7]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [7]
Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B) OTE8GBUR RIR2B_HUMAN Increases Expression [7]
DNA damage-binding protein 2 (DDB2) OTO8HVVB DDB2_HUMAN Increases Expression [7]
Transcription factor E2F8 (E2F8) OTQKZGFP E2F8_HUMAN Increases Expression [10]
Transmembrane protein 250 (TMEM250) OTLJ4G5G TM250_HUMAN Increases Expression [10]
E3 ubiquitin-protein ligase TRIM38 (TRIM38) OT6SP1M9 TRI38_HUMAN Decreases Expression [9]
Torsin-1A (TOR1A) OTYCLGJU TOR1A_HUMAN Decreases Expression [9]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Phosphorylation [16]
Transcription factor EC (TFEC) OTUST8MR TFEC_HUMAN Decreases Expression [9]
Protein phosphatase 1D (PPM1D) OT8NLZ9D PPM1D_HUMAN Increases Expression [9]
Regulator of G-protein signaling 16 (RGS16) OTBKZASI RGS16_HUMAN Increases Expression [9]
E3 ubiquitin-protein ligase RNF113A (RNF113A) OTR6N7HU R113A_HUMAN Decreases Expression [9]
DNA repair protein RAD51 homolog 3 (RAD51C) OTUD6SY5 RA51C_HUMAN Increases Expression [17]
Protein regulator of cytokinesis 1 (PRC1) OTHD0XS0 PRC1_HUMAN Decreases Expression [8]
HMG box-containing protein 1 (HBP1) OTDPGGDV HBP1_HUMAN Decreases Expression [9]
Kinesin-like protein KIF20A (KIF20A) OTXOQHE0 KI20A_HUMAN Decreases Expression [9]
Myelin protein zero-like protein 1 (MPZL1) OTJSUUHR MPZL1_HUMAN Decreases Expression [9]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [16]
Cystatin-A (CSTA) OT1K68KE CYTA_HUMAN Affects Expression [17]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Secretion [18]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Increases Expression [19]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [20]
Endothelin-3 (EDN3) OTN7Q9BE EDN3_HUMAN Decreases Expression [21]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Increases Expression [22]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [23]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Decreases Expression [24]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Increases Expression [22]
Lactoperoxidase (LPO) OTJ9QKX9 PERL_HUMAN Decreases Expression [24]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2) OTIN6G20 CPT2_HUMAN Decreases Expression [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Expression [22]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Increases Expression [22]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [25]
Tripeptidyl-peptidase 2 (TPP2) OT91OVAU TPP2_HUMAN Affects Localization [26]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Increases Expression [22]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Increases Expression [22]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Decreases Expression [24]
Cyclin-dependent kinases regulatory subunit 2 (CKS2) OTPTMHIV CKS2_HUMAN Decreases Expression [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [25]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Expression [24]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [27]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Increases Expression [28]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [28]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Decreases Expression [29]
LIM/homeobox protein Lhx2 (LHX2) OTK61NP8 LHX2_HUMAN Decreases Expression [9]
Max-interacting protein 1 (MXI1) OTUQ9E0D MXI1_HUMAN Decreases Expression [10]
Cyclin-G1 (CCNG1) OT17IA9L CCNG1_HUMAN Increases Expression [25]
Importin subunit alpha-1 (KPNA2) OTU7FOE6 IMA1_HUMAN Decreases Expression [8]
DNA mismatch repair protein Msh6 (MSH6) OT46FP09 MSH6_HUMAN Decreases Expression [9]
Serine/threonine-protein kinase PLK1 (PLK1) OTRZX45T PLK1_HUMAN Decreases Phosphorylation [29]
RecQ-like DNA helicase BLM (BLM) OTEJOAJX BLM_HUMAN Decreases Expression [9]
Ataxin-1 (ATXN1) OTQF0HNR ATX1_HUMAN Decreases Expression [9]
Ras-related protein Rap-2b (RAP2B) OTD2NDQP RAP2B_HUMAN Decreases Expression [9]
Protein BTG2 (BTG2) OTZF6K1H BTG2_HUMAN Increases Expression [9]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Decreases Expression [9]
Runt-related transcription factor 1 (RUNX1) OTU7J84H RUNX1_HUMAN Increases Expression [30]
Histone-lysine N-methyltransferase MECOM (MECOM) OTP983W8 MECOM_HUMAN Increases Expression [30]
Glutamate receptor ionotropic, NMDA 1 (GRIN1) OTZ5YBO8 NMDZ1_HUMAN Decreases Expression [24]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [25]
Unconventional myosin-Ie (MYO1E) OTM9YSIZ MYO1E_HUMAN Decreases Expression [10]
E3 ubiquitin-protein ligase TRIM32 (TRIM32) OTJOV0PG TRI32_HUMAN Decreases Expression [9]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [29]
Oligodendrocyte transcription factor 2 (OLIG2) OTMCN6D3 OLIG2_HUMAN Decreases Expression [24]
Protein BTG3 (BTG3) OT9ANHVT BTG3_HUMAN Decreases Expression [9]
Histone RNA hairpin-binding protein (SLBP) OTVYYQRT SLBP_HUMAN Decreases Expression [9]
Cyclin-dependent kinase 5 activator 1 (CDK5R1) OTJELWK0 CD5R1_HUMAN Increases Expression [10]
Neutral amino acid transporter B(0) (SLC1A5) OTE2H26Q AAAT_HUMAN Decreases Expression [9]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Decreases Expression [24]
Flap endonuclease GEN homolog 1 (GEN1) OT1XFQXF GEN_HUMAN Increases Expression [31]
Borealin (CDCA8) OT17D55D BOREA_HUMAN Decreases Expression [8]
Proline/serine-rich coiled-coil protein 1 (PSRC1) OT7MDJMN PSRC1_HUMAN Decreases Expression [8]
Protein aurora borealis (BORA) OTV2ZPKP BORA_HUMAN Decreases Expression [8]
Leucine-rich repeat-containing protein 47 (LRRC47) OTSE8NAO LRC47_HUMAN Decreases Expression [9]
Lipase member H (LIPH) OTRGYLKL LIPH_HUMAN Decreases Expression [10]
Cytochrome c oxidase assembly factor 7 (COA7) OTRQJYL6 COA7_HUMAN Decreases Expression [9]
Mitochondrial potassium channel (CCDC51) OTOJNHNA MITOK_HUMAN Decreases Expression [9]
Integrator complex subunit 15 (INTS15) OT3O4INM INT15_HUMAN Decreases Expression [9]
Small integral membrane protein 14 (SMIM14) OT47IF19 SIM14_HUMAN Decreases Expression [10]
Growth/differentiation factor 15 (GDF15) OTWQN50N GDF15_HUMAN Increases Expression [9]
Protein pelota homolog (PELO) OTF3WLIM PELO_HUMAN Decreases Expression [9]
TIMELESS-interacting protein (TIPIN) OT9PZHXV TIPIN_HUMAN Decreases Expression [9]
tRNA pseudouridine(38/39) synthase (PUS3) OT6WG6M2 PUS3_HUMAN Decreases Expression [9]
Transmembrane protein 185B (TMEM185B) OTGNYS0J T185B_HUMAN Decreases Expression [9]
Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2) OT3Q11WQ I20L2_HUMAN Decreases Expression [9]
GrpE protein homolog 1, mitochondrial (GRPEL1) OT8O00YJ GRPE1_HUMAN Decreases Expression [9]
Forkhead box protein J2 (FOXJ2) OTPT639J FOXJ2_HUMAN Decreases Expression [9]
Protein CLN8 (CLN8) OT0D4CB5 CLN8_HUMAN Decreases Expression [9]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2) OT9I1XUO CEIP2_HUMAN Decreases Expression [10]
rRNA methyltransferase 2, mitochondrial (MRM2) OTRYA1HU MRM2_HUMAN Decreases Expression [9]
ERBB receptor feedback inhibitor 1 (ERRFI1) OT7VZ2IZ ERRFI_HUMAN Decreases Expression [10]
Frizzled-1 (FZD1) OTZATHVS FZD1_HUMAN Decreases Expression [9]
RING finger protein 24 (RNF24) OTUZI597 RNF24_HUMAN Decreases Expression [10]
DNA polymerase eta (POLH) OTN07WXU POLH_HUMAN Increases Expression [32]
5'-AMP-activated protein kinase subunit beta-1 (PRKAB1) OT1OG4QZ AAKB1_HUMAN Increases Expression [9]
V-type proton ATPase 116 kDa subunit a 2 (ATP6V0A2) OTJBDX0Y VPP2_HUMAN Decreases Expression [24]
Pleckstrin homology-like domain family A member 3 (PHLDA3) OTXFUDO2 PHLA3_HUMAN Increases Expression [9]
Sestrin-1 (SESN1) OTSFDZWL SESN1_HUMAN Increases Expression [9]
Solute carrier family 22 member 4 (SLC22A4) OT4LOVI9 S22A4_HUMAN Increases Uptake [14]
Organic cation/carnitine transporter 2 (SLC22A5) OTC36TYB S22A5_HUMAN Increases Uptake [14]
Urea transporter 1 (SLC14A1) OTH7UUV0 UT1_HUMAN Increases Uptake [14]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Affects Response To Substance [33]
Protein artemis (DCLRE1C) OTW3KB1I DCR1C_HUMAN Increases Response To Substance [11]
Urea transporter 2 (SLC14A2) OTYI6SX1 UT2_HUMAN Increases Uptake [14]
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⏷ Show the Full List of 113 DOT(s)

References

1 ClinicalTrials.gov (NCT04292314) Hydroxy Urea, Omega 3, Nigella Sativa,Honey on Oxidative Stress and Iron Chelation in Pediatric Major Thalassemia
2 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 207384.
3 Deferoxamine FDA Label
4 ClinicalTrials.gov (NCT04333550) Application of Desferal to Treat COVID-19. U.S. National Institutes of Health.
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: 6822).
6 Hydroxyurea FDA Label
7 Differential expression of TP53 associated genes in Fanconi anemia cells after mitomycin C and hydroxyurea treatment. Mutat Res. 2008 Oct 30;656(1-2):1-7.
8 Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
9 Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
10 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
11 Differences in sensitivity to DNA-damaging Agents between XRCC4- and Artemis-deficient human cells. J Radiat Res. 2011;52(4):415-24. doi: 10.1269/jrr.10168.
12 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
13 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.
14 Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
15 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.
16 Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells. Int J Mol Sci. 2020 May 25;21(10):3735. doi: 10.3390/ijms21103735.
17 Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
18 Plasma levels of TNF-alpha in sickle cell patients receiving hydroxyurea. Hematology. 2004 Feb;9(1):61-4. doi: 10.1080/1024533032000158869.
19 Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease. Blood. 2009 Nov 19;114(21):4639-44. doi: 10.1182/blood-2009-04-218040. Epub 2009 Sep 1.
20 Senescence-like changes induced by hydroxyurea in human diploid fibroblasts. Exp Gerontol. 2000 Aug;35(5):553-71. doi: 10.1016/s0531-5565(00)00108-x.
21 Circulating endothelin-3 levels in patients with sickle cell disease during hydroxyurea treatment. Haematologica. 2004 Mar;89(3):360-1.
22 The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents, IV: The mechanisms involved in inhibiting cell-cycle progression. Blood. 2001 Aug 1;98(3):842-50. doi: 10.1182/blood.v98.3.842.
23 Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.
24 Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
25 Hydroxyurea (HU)-induced apoptosis in the mouse fetal lung. Exp Mol Pathol. 2005 Aug;79(1):59-67. doi: 10.1016/j.yexmp.2005.02.007. Epub 2005 Apr 22.
26 MAP kinase-signaling controls nuclear translocation of tripeptidyl-peptidase II in response to DNA damage and oxidative stress. Biochem Biophys Res Commun. 2010 Aug 27;399(3):324-30. doi: 10.1016/j.bbrc.2010.06.133. Epub 2010 Jul 17.
27 Dibutyryl cyclic AMP-induced enhancement of RB protein degradation in human hepatoma cells. Anticancer Res. 1999 Nov-Dec;19(6B):5181-5.
28 Hydroxyurea induces a senescence-like change of K562 human erythroleukemia cell. J Cancer Res Clin Oncol. 2000 Aug;126(8):455-60.
29 PLK1 targets NOTCH1 during DNA damage and mitotic progression. J Biol Chem. 2019 Nov 22;294(47):17941-17950. doi: 10.1074/jbc.RA119.009881. Epub 2019 Oct 9.
30 t(3;21)(q26;q22) in myeloid leukemia: an aggressive syndrome of blast transformation associated with hydroxyurea or antimetabolite therapy. Cancer. 2006 Apr 15;106(8):1730-8. doi: 10.1002/cncr.21797.
31 Expression and localization of GEN1 in mouse mammary epithelial cells. J Biochem Mol Toxicol. 2014 Oct;28(10):450-5. doi: 10.1002/jbt.21584. Epub 2014 Jun 30.
32 Translesion polymerase is upregulated by cancer therapeutics and confers anticancer drug resistance. Cancer Res. 2014 Oct 1;74(19):5585-96. doi: 10.1158/0008-5472.CAN-14-0953. Epub 2014 Aug 14.
33 DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008 Jan;28(2):752-71. doi: 10.1128/MCB.01799-07. Epub 2007 Nov 8.