General Information of Drug Combination (ID: DCKX3NP)

Drug Combination Name
Vismodegib Plicamycin
Indication
Disease Entry Status REF
Papillary renal cell carcinoma Investigative [1]
Component Drugs Vismodegib   DM5IXKQ 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: ACHN
Zero Interaction Potency (ZIP) Score: 18.46
Bliss Independence Score: 22.49
Loewe Additivity Score: 20.54
LHighest Single Agent (HSA) Score: 20.7

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Vismodegib
Disease Entry ICD 11 Status REF
Basal cell carcinoma 2C32 Approved [2]
Primitive neuroectodermal tumour medulloblastoma 2A00.11 Phase 2 [3]
Vismodegib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Smoothened homolog (SMO) TT8J1S3 SMO_HUMAN Modulator [7]
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Vismodegib Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [8]
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Vismodegib Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Increases Expression [9]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [9]
Zinc finger protein GLI1 (GLI1) OT1BTAJO GLI1_HUMAN Decreases Expression [9]
Zinc finger protein GLI2 (GLI2) OTIRV97L GLI2_HUMAN Decreases Expression [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [9]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Expression [9]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [9]
Protein patched homolog 1 (PTCH1) OTMG07H5 PTC1_HUMAN Decreases Expression [9]
Protein smoothened (SMO) OTXXE208 SMO_HUMAN Decreases Expression [9]
Protein patched homolog 2 (PTCH2) OTOQ0K9V PTC2_HUMAN Decreases Expression [9]
Suppressor of fused homolog (SUFU) OT0IRYG1 SUFU_HUMAN Decreases Response To Substance [10]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Decreases Response To Substance [10]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Plicamycin
Disease Entry ICD 11 Status REF
Hypercalcaemia 5B91.0 Approved [4]
Testicular cancer 2C80 Approved [4]
Solid tumour/cancer 2A00-2F9Z Withdrawn from market [5]
Lung cancer 2C25.0 Investigative [6]
Ovarian cancer 2C73 Investigative [6]
Plicamycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RNA synthesis (hRNA synth) TTX2AYW NOUNIPROTAC Modulator [12]
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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 [13]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Expression [14]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [14]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Expression [14]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [15]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [15]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Decreases Expression [16]
Transcription factor Sp1 (SP1) OTISPT4X SP1_HUMAN Decreases Expression [11]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Expression [17]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [18]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Expression [19]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Expression [11]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [20]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Decreases Expression [17]
TNFAIP3-interacting protein 1 (TNIP1) OTRAOTEW TNIP1_HUMAN Decreases Expression [21]
Sphingomyelin phosphodiesterase 3 (SMPD3) OTHQBETH NSMA2_HUMAN Decreases Expression [22]
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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
Breast adenocarcinoma DCLEA4E MDA-MB-468 Investigative [23]
Carcinoma DCBKWNH RXF 393 Investigative [23]
Carcinoma DCGGB2G MCF7 Investigative [23]
Colon adenocarcinoma DCB1RJN COLO 205 Investigative [23]
Colon carcinoma DCIHIS4 KM12 Investigative [23]
Invasive ductal carcinoma DC7MKIN HS 578T Investigative [23]
Invasive ductal carcinoma DC1JVD5 BT-549 Investigative [23]
Invasive ductal carcinoma DCMEQRO T-47D Investigative [23]
Adenocarcinoma DCTXME4 DU-145 Investigative [1]
Adenocarcinoma DCG2MMK OVCAR3 Investigative [1]
Adenocarcinoma DCM5SO5 NCIH23 Investigative [1]
Adenocarcinoma DCVBNR2 A549 Investigative [1]
Adenocarcinoma DCX2KEU SW-620 Investigative [1]
Adenocarcinoma DCKN4FX HT29 Investigative [1]
Adenocarcinoma DCCUBBT HCT116 Investigative [1]
Adenocarcinoma DCQV22I HCC-2998 Investigative [1]
Adenocarcinoma DC1BDZS HCT-15 Investigative [1]
Adult acute myeloid leukemia DCPXMVW HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DCC6DIU MOLT-4 Investigative [1]
Amelanotic melanoma DCCZ9ZH M14 Investigative [1]
Amelanotic melanoma DCGDOKI MDA-MB-435 Investigative [1]
Anaplastic large cell lymphoma DC7NMBP SR Investigative [1]
Astrocytoma DCRJWU1 U251 Investigative [1]
Astrocytoma DCW91Z3 SNB-19 Investigative [1]
Childhood T acute lymphoblastic leukemia DCS9T4Y CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DCZQRX8 K-562 Investigative [1]
Clear cell renal cell carcinoma DCKN4HV TK-10 Investigative [1]
Clear cell renal cell carcinoma DCCHRLV 786-0 Investigative [1]
Clear cell renal cell carcinoma DCHJ0BT A498 Investigative [1]
Clear cell renal cell carcinoma DC73YCW CAKI-1 Investigative [1]
Cutaneous melanoma DCBCLMM SK-MEL-5 Investigative [1]
Cutaneous melanoma DC9TDZB SK-MEL-28 Investigative [1]
Glioblastoma DCJWXRD SNB-75 Investigative [1]
Glioma DCA2JMR SF-539 Investigative [1]
Glioma DCO0DKH SF-268 Investigative [1]
Glioma DCUO9ZK SF-295 Investigative [1]
High grade ovarian serous adenocarcinoma DCQMY29 OVCAR-5 Investigative [1]
High grade ovarian serous adenocarcinoma DC4B6II OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DCG83A6 OVCAR-4 Investigative [1]
Large cell lung carcinoma DCGOKUU NCI-H460 Investigative [1]
Lung adenocarcinoma DC4KTV5 MDA-MB-231 Investigative [1]
Lung adenocarcinoma DCY9RJ5 EKVX Investigative [1]
Lung adenocarcinoma DCB4OVA HOP-62 Investigative [1]
Lung adenocarcinoma DCZQ6NC NCI-H522 Investigative [1]
Malignant melanoma DCSNYNM UACC62 Investigative [1]
Malignant melanoma DC5RVLC LOX IMVI Investigative [1]
Melanoma DCQZCEW SK-MEL-2 Investigative [1]
Melanoma DCFCDEV UACC-257 Investigative [1]
Melanoma DC7AS3H MALME-3M Investigative [1]
Minimally invasive lung adenocarcinoma DC63WZ7 NCI-H322M Investigative [1]
Mixed endometrioid and clear cell carcinoma DC3NCKM IGROV1 Investigative [1]
Non-small cell lung carcinoma DCWU77T HOP-92 Investigative [1]
Ovarian serous cystadenocarcinoma DCZ20C5 SK-OV-3 Investigative [1]
Plasma cell myeloma DC0B4ID RPMI-8226 Investigative [1]
Pleural epithelioid mesothelioma DCVJQT0 NCI-H226 Investigative [1]
Prostate carcinoma DCV43TU PC-3 Investigative [1]
Renal cell carcinoma DCLRXZY UO-31 Investigative [1]
Renal cell carcinoma DCL41I9 SN12C Investigative [1]
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⏷ Show the Full List of 58 DrugCom(s)

References

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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: 6975).
3 A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma. J Am Acad Dermatol. 2015 Jul;73(1):99-105.e1.
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 8394).
6 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
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8 The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7.
9 Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One. 2011;6(11):e27306. doi: 10.1371/journal.pone.0027306. Epub 2011 Nov 8.
10 Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med. 2014 Jul;20(7):732-40. doi: 10.1038/nm.3613. Epub 2014 Jun 29.
11 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.
12 Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.
21 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.
22 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.
23 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.