General Information of Drug Combination (ID: DCUZ4PK)

Drug Combination Name
Romidepsin Valrubicin
Indication
Disease Entry Status REF
Ovarian serous cystadenocarcinoma Investigative [1]
Component Drugs Romidepsin   DMT5GNL Valrubicin   DMOYJFK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: SK-OV-3
Zero Interaction Potency (ZIP) Score: 6.79
Bliss Independence Score: 10.68
Loewe Additivity Score: 8.8
LHighest Single Agent (HSA) Score: 9.3

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Romidepsin
Disease Entry ICD 11 Status REF
Cutaneous T-cell lymphoma 2B01 Approved [2]
Gastrin-producing neuroendocrine tumor N.A. Approved [3]
Glucagonoma N.A. Approved [3]
Insulinoma 2C10.1 Approved [3]
Lung carcinoid tumor N.A. Approved [3]
Melanoma 2C30 Approved [3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [3]
Primary cutaneous T-cell lymphoma N.A. Approved [3]
Urethral cancer 2C93 Approved [3]
Peripheral T-cell lymphoma 2A90.C Phase 3 [4]
Renal cell carcinoma 2C90 Phase 3 [2]
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 [10]
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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 [11]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [11]
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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 [12]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [13]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [14]
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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 [15]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Expression [16]
E3 SUMO-protein ligase CBX4 (CBX4) OT4XVRRF CBX4_HUMAN Increases Expression [17]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [18]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [19]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Increases Expression [20]
Serine/threonine-protein kinase 17B (STK17B) OT4NYNO8 ST17B_HUMAN Increases Expression [17]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Expression [21]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Expression [21]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Expression [21]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [21]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [22]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Increases Expression [17]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [21]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [9]
Transcription factor JunD (JUND) OTNKACJD JUND_HUMAN Increases Expression [17]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [22]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [21]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [22]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [9]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [23]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Phosphorylation [9]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Increases Expression [17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [24]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [21]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [22]
Friend leukemia integration 1 transcription factor (FLI1) OT0EV3LX FLI1_HUMAN Decreases Expression [25]
RNA-binding protein EWS (EWSR1) OT7SRHV3 EWS_HUMAN Decreases Expression [25]
DNA repair protein RAD51 homolog 1 (RAD51) OTNVWGC1 RAD51_HUMAN Decreases Expression [9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [23]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [17]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1) OT6VY3A3 SPTN1_HUMAN Increases Expression [17]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Expression [26]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [23]
Histone H3.1t (H3-4) OTY6ITYF H31T_HUMAN Increases Acetylation [26]
Sodium/iodide cotransporter (SLC5A5) OTU7E9G7 SC5A5_HUMAN Increases Expression [27]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) OT53LJGW M3K3_HUMAN Increases Expression [17]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Affects Metabolism [28]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Response To Substance [29]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Decreases Response To Substance [22]
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⏷ Show the Full List of 41 DOT(s)
Indication(s) of Valrubicin
Disease Entry ICD 11 Status REF
Bladder cancer 2C94 Approved [5]
In situ carcinoma N.A. Approved [6]
Urinary bladder cancer N.A. Approved [6]
Psoriasis vulgaris EA90 Phase 2 [7]
Valrubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Inhibitor [30]
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Valrubicin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [31]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DC4EPFT MOLT-4 Investigative [32]
Anaplastic large cell lymphoma DCUY1GF SR Investigative [32]
Clear cell renal cell carcinoma DCYSS6E A498 Investigative [32]
Clear cell renal cell carcinoma DCVNXTC 786-0 Investigative [32]
Clear cell renal cell carcinoma DC20IEW CAKI-1 Investigative [32]
Papillary renal cell carcinoma DC92CL0 ACHN Investigative [32]
Plasma cell myeloma DCY8QRE RPMI-8226 Investigative [32]
Renal cell carcinoma DC3M47H SN12C Investigative [32]
Carcinoma DCZXCRU MCF7 Investigative [33]
Colon carcinoma DCMBDUU KM12 Investigative [33]
Invasive ductal carcinoma DCNADWX HS 578T Investigative [33]
Adenocarcinoma DCT8H5O NCIH23 Investigative [1]
Adenocarcinoma DC4JSF3 HCC-2998 Investigative [1]
Amelanotic melanoma DC4BGTA MDA-MB-435 Investigative [1]
Amelanotic melanoma DCPLV6P M14 Investigative [1]
High grade ovarian serous adenocarcinoma DCH0KT7 NCI\\/ADR-RES Investigative [1]
Lung adenocarcinoma DCXVAQL HOP-62 Investigative [1]
Minimally invasive lung adenocarcinoma DCNSBOI NCI-H322M Investigative [1]
Non-small cell lung carcinoma DCD3T2V HOP-92 Investigative [1]
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⏷ Show the Full List of 19 DrugCom(s)

References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
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: 7006).
3 Romidepsin FDA Label
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
6 Valrubicin FDA Label
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
8 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.
9 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.
10 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
11 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.
12 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.
13 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.
14 FDA Label of Romidepsin. The 2020 official website of the U.S. Food and Drug Administration.
15 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.
16 Aberrant promoter methylation of the ABCG2 gene in renal carcinoma. Mol Cell Biol. 2006 Nov;26(22):8572-85.
17 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.
18 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.
19 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.
20 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.
21 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.
22 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.
23 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.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.
30 Metabolic activation of N-acylanthracyclines precedes their interaction with DNA topoisomerase II. NCI Monogr. 1987;(4):111-5.
31 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
32 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.
33 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.