Details of the Drug Combination

General Information of Drug Combination (ID: DC3K6RB)

Drug Combination Name
Vismodegib SY-1425
Indication
Disease Entry Status REF
Adult acute myeloid leukemia Investigative [1]
Component Drugs Vismodegib   DM5IXKQ SY-1425   DMH8UF0
Small molecular drug N.A.
High-throughput Screening Result Testing Cell Line: HL-60(TB)
Zero Interaction Potency (ZIP) Score: 23.22
Bliss Independence Score: 23.72
Loewe Additivity Score: 14.05
LHighest Single Agent (HSA) Score: 22.07

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 [5]
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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 [6]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [6]
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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 [7]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [7]
Zinc finger protein GLI1 (GLI1) OT1BTAJO GLI1_HUMAN Decreases Expression [7]
Zinc finger protein GLI2 (GLI2) OTIRV97L GLI2_HUMAN Decreases Expression [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [7]
Platelet-derived growth factor receptor alpha (PDGFRA) OTDJXUCN PGFRA_HUMAN Decreases Expression [7]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [7]
Protein patched homolog 1 (PTCH1) OTMG07H5 PTC1_HUMAN Decreases Expression [7]
Protein smoothened (SMO) OTXXE208 SMO_HUMAN Decreases Expression [7]
Protein patched homolog 2 (PTCH2) OTOQ0K9V PTC2_HUMAN Decreases Expression [7]
Suppressor of fused homolog (SUFU) OT0IRYG1 SUFU_HUMAN Decreases Response To Substance [8]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Decreases Response To Substance [8]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of SY-1425
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Phase 1 [4]
Myelodysplastic syndrome 2A37 Phase 1 [4]
SY-1425 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Retinoic acid receptor alpha (RARA) TTW38KT RARA_HUMAN Agonist [4]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Invasive ductal carcinoma DC47ESM T-47D Investigative [9]
Adenocarcinoma DC64GFT NCIH23 Investigative [1]
Anaplastic large cell lymphoma DC20KFI SR Investigative [1]
Chronic myelogenous leukemia DC9SCRX K-562 Investigative [1]
Cutaneous melanoma DCY4JSZ SK-MEL-5 Investigative [1]
Large cell lung carcinoma DCI34HU NCI-H460 Investigative [1]
Malignant melanoma DCHUDOA LOX IMVI Investigative [1]
Melanoma DCQZPQM MALME-3M Investigative [1]
Minimally invasive lung adenocarcinoma DC5RESX NCI-H322M Investigative [1]
Prostate carcinoma DCSA2CS PC-3 Investigative [1]
Renal cell carcinoma DC8YA03 UO-31 Investigative [1]
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⏷ Show the Full List of 11 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: 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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
6 The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7.
7 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.
8 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.
9 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.