General Information of Drug Combination (ID: DCEHX1L)

Drug Combination Name
Indazole derivative 5 Plicamycin
Indication
Disease Entry Status REF
Melanoma Investigative [1]
Component Drugs Indazole derivative 5   DMM1I8R Plicamycin   DM7C8YV
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: UACC-257
Zero Interaction Potency (ZIP) Score: 10.12
Bliss Independence Score: 12.44
Loewe Additivity Score: 13.34
LHighest Single Agent (HSA) Score: 11.65

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indazole derivative 5 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ABL T315I mutant (ABL T315I) TTZJTWA ABL1_HUMAN Inhibitor [5]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I) TTIV39N BCR_HUMAN-ABL1_HUMAN Inhibitor [5]
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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Solid tumour/cancer 2A00-2F9Z Withdrawn from market [3]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 [7]
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Plicamycin Interacts with 16 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 [8]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [9]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [9]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [9]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [10]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [10]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [11]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [6]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [12]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [13]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [14]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [6]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [15]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [12]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [16]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [17]
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⏷ Show the Full List of 16 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCUMFTB HL-60(TB) Investigative [18]
Adult T acute lymphoblastic leukemia DCPAJ95 MOLT-4 Investigative [18]
Anaplastic large cell lymphoma DCRHUXF SR Investigative [18]
Astrocytoma DC9FAPK SNB-19 Investigative [18]
Chronic myelogenous leukemia DC6VYXF K-562 Investigative [18]
Clear cell renal cell carcinoma DCF2XJ0 A498 Investigative [18]
Clear cell renal cell carcinoma DC3M1GY 786-0 Investigative [18]
Clear cell renal cell carcinoma DCB9QWN TK-10 Investigative [18]
Clear cell renal cell carcinoma DCQBU9J CAKI-1 Investigative [18]
Glioblastoma DCY0AHD SNB-75 Investigative [18]
Glioma DCHPYBC SF-295 Investigative [18]
Papillary renal cell carcinoma DCFJYS8 ACHN Investigative [18]
Plasma cell myeloma DCI9O4R RPMI-8226 Investigative [18]
Renal cell carcinoma DCFAM6W UO-31 Investigative [18]
Breast adenocarcinoma DC4KB76 MDA-MB-468 Investigative [19]
Carcinoma DCNT3XE MCF7 Investigative [19]
Colon adenocarcinoma DCCAG7O COLO 205 Investigative [19]
Colon carcinoma DC62AHJ KM12 Investigative [19]
Invasive ductal carcinoma DCO8X0V BT-549 Investigative [19]
Invasive ductal carcinoma DCK3F0N T-47D Investigative [19]
Invasive ductal carcinoma DCDMYCJ HS 578T Investigative [19]
Adenocarcinoma DCZG6WP DU-145 Investigative [1]
Adenocarcinoma DCCCLGJ OVCAR3 Investigative [1]
Adenocarcinoma DC4Q8XF HCC-2998 Investigative [1]
Adenocarcinoma DC659YG HT29 Investigative [1]
Amelanotic melanoma DCDCF5O MDA-MB-435 Investigative [1]
Amelanotic melanoma DC8EKGK M14 Investigative [1]
Cutaneous melanoma DCW5TKR SK-MEL-5 Investigative [1]
High grade ovarian serous adenocarcinoma DCHTQRX OVCAR-4 Investigative [1]
High grade ovarian serous adenocarcinoma DCXFSYB OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DCDLKVS OVCAR-5 Investigative [1]
High grade ovarian serous adenocarcinoma DC1V6R7 NCI\\/ADR-RES Investigative [1]
Lung adenocarcinoma DC4DQKT MDA-MB-231 Investigative [1]
Malignant melanoma DCKJGRV LOX IMVI Investigative [1]
Melanoma DCU5XVY MALME-3M Investigative [1]
Melanoma DC66JV2 SK-MEL-2 Investigative [1]
Minimally invasive lung adenocarcinoma DC3LJKY NCI-H322M Investigative [1]
Mixed endometrioid and clear cell carcinoma DCUTBHH IGROV1 Investigative [1]
Ovarian serous cystadenocarcinoma DC32BYX SK-OV-3 Investigative [1]
Prostate carcinoma DC1XBEP PC-3 Investigative [1]
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⏷ Show the Full List of 40 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 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 Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
6 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.
7 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
8 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.
9 Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression. Toxicol Appl Pharmacol. 2014 Oct 1;280(1):138-48.
10 Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
11 Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter. Gene. 2014 Feb 15;536(1):135-44. doi: 10.1016/j.gene.2013.11.053. Epub 2013 Dec 4.
12 Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
13 Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. Lung. 2004;182(4):251-64. doi: 10.1007/s00408-004-2507-2.
14 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.
15 CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
16 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.
17 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.
18 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.
19 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.