Details of the Drug Combination

General Information of Drug Combination (ID: DCAB9X9)

Drug Combination Name
Artesunate Romidepsin
Indication
Disease Entry Status REF
Hiv Phase 2 [1]
Component Drugs Artesunate   DMR27C8 Romidepsin   DMT5GNL
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 Artesunate
Disease Entry ICD 11 Status REF
Infection of P. falciparum 1F40 Approved [2]
Malaria 1F40-1F45 Approved [3]
Plasmodium falciparum malaria 1F40 Approved [2]
Artesunate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A) TTZVSJ2 NOUNIPROTAC Inhibitor [3]
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Artesunate Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [10]
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Artesunate Interacts with 57 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Catalase (CAT) OTHEBX9R CATA_HUMAN Increases Expression [7]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [7]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Expression [7]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [7]
Serine/threonine-protein kinase Chk1 (CHEK1) OTTTI622 CHK1_HUMAN Increases Phosphorylation [11]
Ubiquitin-like protein ATG12 (ATG12) OTJRO09Y ATG12_HUMAN Increases Expression [12]
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Affects Localization [13]
Serine/threonine-protein kinase Chk2 (CHEK2) OT8ZPCNS CHK2_HUMAN Increases Phosphorylation [11]
Metalloproteinase inhibitor 1 (TIMP1) OTOXC51H TIMP1_HUMAN Increases Expression [12]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Decreases Expression [12]
Ferritin heavy chain (FTH1) OT6IFS0O FRIH_HUMAN Decreases Expression [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [14]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [13]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [13]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [12]
Replication protein A 32 kDa subunit (RPA2) OTZ54WAF RFA2_HUMAN Increases Phosphorylation [11]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [11]
Desmin (DES) OTI09KBW DESM_HUMAN Decreases Expression [12]
Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4) OTRAFFX2 GPX4_HUMAN Decreases Activity [12]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [8]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Affects Expression [13]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [12]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [13]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [12]
Nuclear receptor coactivator 4 (NCOA4) OTRVU0UA NCOA4_HUMAN Decreases Expression [12]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Affects Localization [15]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) OTUYHB84 MLP3B_HUMAN Increases Lipidation [8]
Autophagy protein 5 (ATG5) OT4T5SMS ATG5_HUMAN Increases Expression [12]
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) OTPL0AI1 ABC3C_HUMAN Increases Expression [11]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3) OT28VBVK ATG3_HUMAN Increases Expression [12]
Small ribosomal subunit protein uS8 (RPS15A) OT0BUA12 RS15A_HUMAN Decreases Response To Substance [9]
Mitochondrial thiamine pyrophosphate carrier (SLC25A19) OT157TY3 TPC_HUMAN Decreases Response To Substance [9]
Atypical kinase COQ8A, mitochondrial (COQ8A) OT1ETSA2 COQ8A_HUMAN Decreases Response To Substance [9]
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2) OT1LQSGX MTDC_HUMAN Decreases Response To Substance [9]
Large ribosomal subunit protein uL30 (RPL7) OT4WCQBE RL7_HUMAN Decreases Response To Substance [9]
Glutamate--cysteine ligase regulatory subunit (GCLM) OT6CP234 GSH0_HUMAN Decreases Response To Substance [16]
Integrin beta-1 (ITGB1) OT6G1IAR ITB1_HUMAN Increases Response To Substance [9]
CAP-Gly domain-containing linker protein 4 (CLIP4) OT75KVQK CLIP4_HUMAN Increases Response To Substance [9]
Glutathione S-transferase theta-2 (GSTT2) OTANW3TJ GST2_HUMAN Affects Response To Substance [16]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1) OTAV5SE7 BST1_HUMAN Increases Response To Substance [9]
Small ribosomal subunit protein eS12 (RPS12) OTBRQ8MS RS12_HUMAN Decreases Response To Substance [9]
Dopamine beta-hydroxylase (DBH) OTC6I2SP DOPO_HUMAN Increases Response To Substance [9]
Glutamate--cysteine ligase catalytic subunit (GCLC) OTESDI4D GSH1_HUMAN Decreases Response To Substance [16]
Nck-associated protein 1 (NCKAP1) OTEZQXXJ NCKP1_HUMAN Increases Response To Substance [9]
Small ribosomal subunit protein eS32 (RPL41) OTFW5IFO RS32_HUMAN Decreases Response To Substance [9]
Translationally-controlled tumor protein (TPT1) OTHMTRJU TCTP_HUMAN Affects Response To Substance [17]
Nascent polypeptide-associated complex subunit alpha (NACA) OTLP1KR3 NACA_HUMAN Decreases Response To Substance [9]
Glutathione S-transferase Mu 4 (GSTM4) OTOTF8DU GSTM4_HUMAN Affects Response To Substance [16]
Maleylacetoacetate isomerase (GSTZ1) OTQ43JCE MAAI_HUMAN Affects Response To Substance [16]
Large ribosomal subunit protein eL6 (RPL6) OTRU71O4 RL6_HUMAN Decreases Response To Substance [9]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Response To Substance [9]
Frizzled-7 (FZD7) OTTK3F6E FZD7_HUMAN Increases Response To Substance [9]
Serine/arginine-rich splicing factor 2 (SRSF2) OTVDHO6U SRSF2_HUMAN Decreases Response To Substance [9]
T-complex protein 1 subunit beta (CCT2) OTW1VV4E TCPB_HUMAN Decreases Response To Substance [9]
Glutathione S-transferase 3, mitochondrial (MGST3) OTYK80JA MGST3_HUMAN Affects Response To Substance [16]
Filamin-A (FLNA) OTYZ9JXM FLNA_HUMAN Increases Response To Substance [9]
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⏷ Show the Full List of 57 DOT(s)
Indication(s) of Romidepsin
Disease Entry ICD 11 Status REF
Cutaneous T-cell lymphoma 2B01 Approved [4]
Gastrin-producing neuroendocrine tumor N.A. Approved [5]
Glucagonoma N.A. Approved [5]
Insulinoma 2C10.1 Approved [5]
Lung carcinoid tumor N.A. Approved [5]
Melanoma 2C30 Approved [5]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [5]
Primary cutaneous T-cell lymphoma N.A. Approved [5]
Urethral cancer 2C93 Approved [5]
Peripheral T-cell lymphoma 2A90.C Phase 3 [6]
Renal cell carcinoma 2C90 Phase 3 [4]
Romidepsin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Histone deacetylase 1 (HDAC1) TT6R7JZ HDAC1_HUMAN Inhibitor [20]
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Romidepsin Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [21]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [21]
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Romidepsin Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [22]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [23]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [24]
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Romidepsin Interacts with 41 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [25]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Expression [26]
E3 SUMO-protein ligase CBX4 (CBX4) OT4XVRRF CBX4_HUMAN Increases Expression [27]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [28]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [29]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [30]
Serine/threonine-protein kinase 17B (STK17B) OT4NYNO8 ST17B_HUMAN Increases Expression [27]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [31]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Expression [31]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Expression [31]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [31]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [32]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Increases Expression [27]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [31]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [19]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [27]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [32]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [31]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [32]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [19]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [19]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [33]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Phosphorylation [19]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Increases Expression [27]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [34]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [31]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [32]
Friend leukemia integration 1 transcription factor (FLI1) OT0EV3LX FLI1_HUMAN Decreases Expression [35]
RNA-binding protein EWS (EWSR1) OT7SRHV3 EWS_HUMAN Decreases Expression [35]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [19]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [33]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [27]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1) OT6VY3A3 SPTN1_HUMAN Increases Expression [27]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Expression [36]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [33]
Histone H3.1t (H3-4) OTY6ITYF H31T_HUMAN Increases Acetylation [36]
Sodium/iodide cotransporter (SLC5A5) OTU7E9G7 SC5A5_HUMAN Increases Expression [37]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) OT53LJGW M3K3_HUMAN Increases Expression [27]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Affects Metabolism [38]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Response To Substance [39]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Response To Substance [32]
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⏷ Show the Full List of 41 DOT(s)

References

1 ClinicalTrials.gov (NCT03041012) Early Administration of Romidepsin and 3BNC117 in Treatment-nave HIV Patients Starting ART
2 Artesunate FDA Label
3 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
4 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: 7006).
5 Romidepsin FDA Label
6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7 Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. Int J Oncol. 2009 Jul;35(1):149-58.
8 Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells. Chem Biol Interact. 2020 Nov 1;331:109273. doi: 10.1016/j.cbi.2020.109273. Epub 2020 Sep 28.
9 Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.
10 Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42.
11 Induction of APOBEC3C Facilitates the Genotoxic Stress-Mediated Cytotoxicity of Artesunate. Chem Res Toxicol. 2019 Dec 16;32(12):2526-2537. doi: 10.1021/acs.chemrestox.9b00358. Epub 2019 Nov 11.
12 Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother. 2019 Jan;109:2043-2053. doi: 10.1016/j.biopha.2018.11.030. Epub 2018 Nov 26.
13 Artesunate induces apoptosis through caspase-dependent and -independent mitochondrial pathways in human myelodysplastic syndrome SKM-1 cells. Chem Biol Interact. 2014 Aug 5;219:28-36. doi: 10.1016/j.cbi.2014.03.011. Epub 2014 Apr 3.
14 AMG900 as novel inhibitor of the translationally controlled tumor protein. Chem Biol Interact. 2021 Jan 25;334:109349. doi: 10.1016/j.cbi.2020.109349. Epub 2020 Nov 28.
15 Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
16 Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. In Vivo. 2005 Jan-Feb;19(1):225-32.
17 Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. Drug Resist Updat. 2005 Feb-Apr;8(1-2):85-97. doi: 10.1016/j.drup.2005.04.003.
18 Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin. Fertil Steril. 2011 Apr;95(5):1579-83. doi: 10.1016/j.fertnstert.2010.12.058. Epub 2011 Feb 4.
19 Inhibitors of class I HDACs and of FLT3 combine synergistically against leukemia cells with mutant FLT3. Arch Toxicol. 2022 Jan;96(1):177-193. doi: 10.1007/s00204-021-03174-1. Epub 2021 Oct 19.
20 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
21 Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503.
22 A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03. Neuro Oncol. 2011 May;13(5):509-16.
23 Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503.
24 FDA Label of Romidepsin. The 2020 official website of the U.S. Food and Drug Administration.
25 Chemoresistance to depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is mediated by reversible MDR1 induction in human cancer cell lines. J Pharmacol Exp Ther. 2005 Jul;314(1):467-75. doi: 10.1124/jpet.105.083956. Epub 2005 Apr 15.
26 Aberrant promoter methylation of the ABCG2 gene in renal carcinoma. Mol Cell Biol. 2006 Nov;26(22):8572-85.
27 5-Aza-2'-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer). Biochem Biophys Res Commun. 2006 Dec 15;351(2):455-61. doi: 10.1016/j.bbrc.2006.10.055. Epub 2006 Oct 18.
28 Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity. Cancer Res. 2006 Jul 15;66(14):7317-25. doi: 10.1158/0008-5472.CAN-06-0680.
29 Histone deacetylase inhibitors FK228, N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)amino- methyl]benzamide and m-carboxycinnamic acid bis-hydroxamide augment radiation-induced cell death in gastrointestinal adenocarcinoma cells. Int J Cancer. 2004 Jun 10;110(2):301-8. doi: 10.1002/ijc.20117.
30 A sequential treatment of depsipeptide followed by 5-azacytidine enhances Gadd45beta expression in hepatocellular carcinoma cells. Anticancer Res. 2007 Nov-Dec;27(6B):3783-9.
31 Abrogation of p21 expression by flavopiridol enhances depsipeptide-mediated apoptosis in malignant pleural mesothelioma cells. Clin Cancer Res. 2004 Mar 1;10(5):1813-25. doi: 10.1158/1078-0432.ccr-0901-3.
32 Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells. Clin Cancer Res. 2008 Jan 15;14(2):549-58. doi: 10.1158/1078-0432.CCR-07-1934.
33 Blocking downstream signaling pathways in the context of HDAC inhibition promotes apoptosis preferentially in cells harboring mutant Ras. Oncotarget. 2016 Oct 25;7(43):69804-69815. doi: 10.18632/oncotarget.12001.
34 Up-regulation of MDR1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (FK228) and ATRA in acute promyelocytic leukemia cells. Blood. 2006 Feb 15;107(4):1546-54. doi: 10.1182/blood-2004-10-4126. Epub 2005 Oct 13.
35 Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors. Int J Cancer. 2005 Sep 20;116(5):784-92. doi: 10.1002/ijc.21069.
36 Enhanced transgene expression in urothelial cancer gene therapy with histone deacetylase inhibitor. J Urol. 2005 Aug;174(2):747-52. doi: 10.1097/01.ju.0000164723.20555.e6.
37 Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer. 2006 Sep;13(3):797-826. doi: 10.1677/erc.1.01143.
38 Identification of cytochrome P450 enzymes involved in the metabolism of FK228, a potent histone deacetylase inhibitor, in human liver microsomes. Biol Pharm Bull. 2005 Jan;28(1):124-9.
39 Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing's sarcoma cells. Int J Cancer. 2006 Jan 1;118(1):90-7. doi: 10.1002/ijc.21297.