General Information of Drug Combination (ID: DC4T49Z)

Drug Combination Name
Plicamycin Chlorambucil
Indication
Disease Entry Status REF
Clear cell renal cell carcinoma Investigative [1]
Component Drugs Plicamycin   DM7C8YV Chlorambucil   DMRKE63
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: TK-10
Zero Interaction Potency (ZIP) Score: 2.66
Bliss Independence Score: 4.03
Loewe Additivity Score: 1.11
LHighest Single Agent (HSA) Score: 2.04

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [2]
Testicular cancer 2C80 Approved [2]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [3]
Lung cancer 2C25.0 Investigative [4]
Ovarian cancer 2C73 Investigative [4]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [8]
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Plicamycin Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Expression [9]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [10]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [11]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [12]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [7]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [11]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [13]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [14]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Chlorambucil
Disease Entry ICD 11 Status REF
Chronic lymphocytic leukaemia 2A82.0 Approved [5]
Small lymphocytic lymphoma 2A82.0 Approved [6]
Classic Hodgkin lymphoma N.A. Investigative [6]
Follicular lymphoma 2A80 Investigative [6]
Chlorambucil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA replication (DNA repli) TTABD5E NOUNIPROTAC Intercalator [15]
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Chlorambucil Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [16]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [17]
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Chlorambucil Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [18]
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Chlorambucil Interacts with 21 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [19]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Decreases Expression [20]
Aldo-keto reductase family 1 member C2 (AKR1C2) OTQ2XMO3 AK1C2_HUMAN Decreases Expression [20]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [20]
F-box only protein 30 (FBXO30) OTD1P6LA FBX30_HUMAN Decreases Expression [20]
Histone chaperone ASF1A (ASF1A) OT4S44GP ASF1A_HUMAN Decreases Expression [20]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Affects Expression [21]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [22]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Affects Expression [23]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [24]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [25]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1) OT7OG7Y2 DPA1_HUMAN Affects Expression [26]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [27]
14-3-3 protein sigma (SFN) OTLJCZ1U 1433S_HUMAN Increases Expression [22]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [28]
Histone H4 (H4C1) OTB71W46 H4_HUMAN Decreases Expression [25]
kinase isozyme 4, mitochondrial (PDK4) OTCMHMBZ PDK4_HUMAN Affects Expression [29]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [23]
Fanconi anemia group G protein (FANCG) OT7MC8TZ FANCG_HUMAN Increases Response To Substance [30]
Baculoviral IAP repeat-containing protein 2 (BIRC2) OTFXFREP BIRC2_HUMAN Decreases Response To Substance [31]
Fanconi anemia group C protein (FANCC) OTTIDM3P FANCC_HUMAN Increases Response To Substance [30]
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⏷ Show the Full List of 21 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult T acute lymphoblastic leukemia DCFMYUH MOLT-4 Investigative [1]
Childhood T acute lymphoblastic leukemia DCY9LX0 CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DCBPG8U K-562 Investigative [1]
Papillary renal cell carcinoma DCDQ2K1 ACHN Investigative [1]
Breast adenocarcinoma DCV0MWR MDA-MB-468 Investigative [32]
Invasive ductal carcinoma DC8UGUM T-47D Investigative [32]
Adenocarcinoma DC0NGWR HCT116 Investigative [33]
High grade ovarian serous adenocarcinoma DCZPIWH OVCAR-5 Investigative [33]
Ovarian serous cystadenocarcinoma DCLVOU2 SK-OV-3 Investigative [33]
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⏷ Show the Full List of 9 DrugCom(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
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: 8394).
4 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
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: 7143).
6 Chlorambucil FDA Label
7 The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
8 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
9 SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
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12 The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
13 Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
14 Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
15 Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A. Mol Cancer Ther. 2009 Jun;8(6):1714-23.
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18 The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol. 2008 Jun 27;380(1):131-44.
19 Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
20 Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
21 Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene. 2003 Nov 13;22(51):8356-69. doi: 10.1038/sj.onc.1207004.
22 Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells. J Cell Biochem. 2008 May 15;104(2):595-605. doi: 10.1002/jcb.21649.
23 Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70. J Cell Physiol. 2007 Oct;213(1):229-36. doi: 10.1002/jcp.21116.
24 Theophylline synergizes with chlorambucil in inducing apoptosis of B-chronic lymphocytic leukemia cells. Blood. 1996 Sep 15;88(6):2172-82.
25 A two-hit mechanism for pre-mitotic arrest of cancer cell proliferation by a polyamide-alkylator conjugate. Cell Cycle. 2006 Jul;5(14):1537-48. doi: 10.4161/cc.5.14.2913. Epub 2006 Jul 17.
26 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
27 Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
28 Disruption of gene expression and induction of apoptosis in prostate cancer cells by a DNA-damaging agent tethered to an androgen receptor ligand. Chem Biol. 2005 Jul;12(7):779-87. doi: 10.1016/j.chembiol.2005.05.009.
29 The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
30 In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res. 2005 Oct 15;11(20):7508-15. doi: 10.1158/1078-0432.CCR-05-1048.
31 Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
32 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
33 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976