Details of the Drug Combination

General Information of Drug Combination (ID: DCK529K)

• Drug Combination Name: LGK974 + LGX818
• Indication: Metastatic Colorectal Cancer; Status: Phase 1 [1]
• Component Drugs:
  LGK974 (DMAG6BV): Small molecular drug
  LGX818 (DMNQXV8): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of LGK974

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

LGK974 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Protein-serine O-palmitoleoyltransferase porcupine (PORCN)	TTNFBTO	PORCN_HUMAN	Inhibitor	[4]

Indication(s) of LGX818

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[3]

LGX818 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Modulator	[5]

LGX818 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]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[6]

References

• [1] ClinicalTrials.gov (NCT02278133) Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations
• [2] Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20224-9.
• [3] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [6] Development of encorafenib for BRAF-mutated advanced melanoma. Curr Opin Oncol. 2018 Mar;30(2):125-133.