Details of the Drug Combination

General Information of Drug Combination (ID: DCE4S9Z)

Drug Combination Name

Vismodegib Indazole derivative 5

Indication

Disease Entry	Status	REF
Invasive ductal carcinoma	Investigative	[1]

Component Drugs

Vismodegib DM5IXKQ

Indazole derivative 5 DMM1I8R

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: BT-549

Zero Interaction Potency (ZIP) Score: 1.59

Bliss Independence Score: 3.69

Loewe Additivity Score: 1.53

LHighest Single Agent (HSA) Score: 1.88

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	[4]
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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	[5]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[5]
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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	[6]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[6]
Zinc finger protein GLI1 (GLI1)	OT1BTAJO	GLI1_HUMAN	Decreases Expression	[6]
Zinc finger protein GLI2 (GLI2)	OTIRV97L	GLI2_HUMAN	Decreases Expression	[6]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[6]
Platelet-derived growth factor receptor alpha (PDGFRA)	OTDJXUCN	PGFRA_HUMAN	Decreases Expression	[6]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[6]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[6]
Protein patched homolog 1 (PTCH1)	OTMG07H5	PTC1_HUMAN	Decreases Expression	[6]
Protein smoothened (SMO)	OTXXE208	SMO_HUMAN	Decreases Expression	[6]
Protein patched homolog 2 (PTCH2)	OTOQ0K9V	PTC2_HUMAN	Decreases Expression	[6]
Suppressor of fused homolog (SUFU)	OT0IRYG1	SUFU_HUMAN	Decreases Response To Substance	[7]
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Decreases Response To Substance	[7]
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⏷ Show the Full List of 13 DOT(s)

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	[8]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[8]
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Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DCX8AMS	MDA-MB-468	Investigative	[1]
Colon adenocarcinoma	DCH4TZ4	COLO 205	Investigative	[1]
Adenocarcinoma	DCV1OJ8	DU-145	Investigative	[9]
Adenocarcinoma	DCL6BWE	NCIH23	Investigative	[9]
Adult T acute lymphoblastic leukemia	DCMXN3J	MOLT-4	Investigative	[9]
Amelanotic melanoma	DCQAU75	M14	Investigative	[9]
Astrocytoma	DCTK2ZT	U251	Investigative	[9]
Clear cell renal cell carcinoma	DCV4ZSQ	TK-10	Investigative	[9]
Clear cell renal cell carcinoma	DCA2QGR	CAKI-1	Investigative	[9]
Cutaneous melanoma	DCWRHP8	SK-MEL-5	Investigative	[9]
Cutaneous melanoma	DC7X3TP	SK-MEL-28	Investigative	[9]
Glioblastoma	DCV4LX3	SNB-75	Investigative	[9]
High grade ovarian serous adenocarcinoma	DCFK8RC	OVCAR-8	Investigative	[9]
Lung adenocarcinoma	DCW3R2D	MDA-MB-231	Investigative	[9]
Lung adenocarcinoma	DCJG3EI	EKVX	Investigative	[9]
Lung adenocarcinoma	DCOID1N	HOP-62	Investigative	[9]
Melanoma	DC97S2G	UACC-257	Investigative	[9]
Melanoma	DCSW5V8	SK-MEL-2	Investigative	[9]
Non-small cell lung carcinoma	DC4A9HY	HOP-92	Investigative	[9]
Ovarian serous cystadenocarcinoma	DC1UX16	SK-OV-3	Investigative	[9]
Papillary renal cell carcinoma	DCN5VQH	ACHN	Investigative	[9]
Plasma cell myeloma	DC6UCGN	RPMI-8226	Investigative	[9]
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⏷ Show the Full List of 22 DrugCom(s)

References

1	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.
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	Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
5	The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7.
6	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.
7	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.
8	Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
9	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.