General Information of Drug Combination (ID: DCXYRND)

Drug Combination Name
Raloxifene Vismodegib
Indication
Disease Entry Status REF
Adult T acute lymphoblastic leukemia Investigative [1]
Component Drugs Raloxifene   DMDKF3M Vismodegib   DM5IXKQ
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MOLT-4
Zero Interaction Potency (ZIP) Score: 8
Bliss Independence Score: 15.6
Loewe Additivity Score: 9.75
LHighest Single Agent (HSA) Score: 10.35

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Raloxifene
Disease Entry ICD 11 Status REF
Osteoporosis FB83.0 Approved [2]
Raloxifene Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Modulator [5]
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Raloxifene Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
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Raloxifene Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [8]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DEL5N6Y UD110_HUMAN Metabolism [9]
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Indication(s) of Vismodegib
Disease Entry ICD 11 Status REF
Basal cell carcinoma 2C32 Approved [3]
Primitive neuroectodermal tumour medulloblastoma 2A00.11 Phase 2 [4]
Vismodegib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Smoothened homolog (SMO) TT8J1S3 SMO_HUMAN Modulator [10]
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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 [11]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [11]
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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 [12]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [12]
Zinc finger protein GLI1 (GLI1) OT1BTAJO GLI1_HUMAN Decreases Expression [12]
Zinc finger protein GLI2 (GLI2) OTIRV97L GLI2_HUMAN Decreases Expression [12]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [12]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Expression [12]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [12]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [12]
Protein patched homolog 1 (PTCH1) OTMG07H5 PTC1_HUMAN Decreases Expression [12]
Protein smoothened (SMO) OTXXE208 SMO_HUMAN Decreases Expression [12]
Protein patched homolog 2 (PTCH2) OTOQ0K9V PTC2_HUMAN Decreases Expression [12]
Suppressor of fused homolog (SUFU) OT0IRYG1 SUFU_HUMAN Decreases Response To Substance [13]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Decreases Response To Substance [13]
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⏷ Show the Full List of 13 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Clear cell renal cell carcinoma DCI5WC5 TK-10 Investigative [1]
Invasive ductal carcinoma DCG5Y8E BT-549 Investigative [14]
Adenocarcinoma DCZNZPP DU-145 Investigative [15]
Adenocarcinoma DCEOVE3 HCC-2998 Investigative [15]
Large cell lung carcinoma DCJZ3UW NCI-H460 Investigative [15]
Malignant melanoma DCMXE2H UACC62 Investigative [15]
Malignant melanoma DC6ZGTO LOX IMVI Investigative [15]
Melanoma DC2MKCB UACC-257 Investigative [15]
Mixed endometrioid and clear cell carcinoma DCOBJRG IGROV1 Investigative [15]
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⏷ Show the Full List of 9 DrugCom(s)

References

1 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.
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: 6975).
4 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.
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. (Target id: 620).
6 Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308.
7 The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
8 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
9 Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.
10 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
11 The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7.
12 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.
13 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.
14 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.
15 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.