Details of the Drug Combination

General Information of Drug Combination (ID: DC993H4)

Drug Combination Name

ARRY-162 LEE011

Indication

Disease Entry	Status	REF
Solid Tumors Harboring a BRAF V600 Mutation	Phase 1	[1]

Component Drugs

ARRY-162 DM1P6FR

LEE011 DMMX75K

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of ARRY-162

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[2]

ARRY-162 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Modulator	[5]
ERK activator kinase (MEK)	TTZCRP3	NOUNIPROTAC	Inhibitor	[2]
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ARRY-162 Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[6]
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ARRY-162 Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[8]
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Indication(s) of LEE011

LEE011 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Modulator	[9]
Cyclin-dependent kinase 6 (CDK6)	TTO0FDJ	CDK6_HUMAN	Modulator	[9]
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LEE011 Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[10]
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Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Locally Advanced or Metastatic NRAS Mutant Melanoma	DCPPDY6	N. A.	Phase 1	[11]
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References

1	ClinicalTrials.gov (NCT01543698) A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
2	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	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: 7383).
5	MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
6	The impact of P-glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors. Int J Cancer. 2018 Jan 15;142(2):381-391.
7	FDA Label of Binimetinib. The 2020 official website of the U.S. Food and Drug Administration.
8	Binimetinib - European Medicines Agency - European Union
9	Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
10	Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
11	ClinicalTrials.gov (NCT01781572) A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma