Details of the Drug

General Information of Drug (ID: DMNQXV8)

• Drug Name: LGX818
• Synonyms: Encorafenib; 1269440-17-6; LGX-818; Encorafenib (LGX818); UNII-8L7891MRB6; LGX 818; 8L7891MRB6; Encorafenib [USAN:INN]; LGX-818(Encorafenib)

Indication

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[1]

• Affected Organisms: Humans and other mammals
• ATC Code:
  L01EC03: LGX818
  L01EC: B-Raf serine-threonine kinase (BRAF) inhibitors
  L01E: PROTEIN KINASE INHIBITORS
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 540
  Logarithm of the Partition Coefficient (xlogp); 2.7
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 10
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2 h []
  Clearance: The clearance of drug is 14 L/h []
  Elimination: 47% (5% unchanged) of the administered dose was recovered in the feces and 47% (2% unchanged) was recovered in the urine []
  Half-life: The concentration or amount of drug in body reduced by one-half in 3.5 hours []
  Metabolism: The drug is metabolized via the liver []
  Vd: The volume of distribution (Vd) of drug is 164 L []
• Chemical Identifiers:
  Formula: C22H27ClFN7O4S
  IUPAC Name: methyl N-[(2S)-1-[[4-[3-[5-chloro-2-fluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate
  Canonical SMILES: C[C@@H](CNC1=NC=CC(=N1)C2=CN(N=C2C3=C(C(=CC(=C3)Cl)NS(=O)(=O)C)F)C(C)C)NC(=O)OC
  InChI: InChI=1S/C22H27ClFN7O4S/c1-12(2)31-11-16(17-6-7-25-21(28-17)26-10-13(3)27-22(32)35-4)20(29-31)15-8-14(23)9-18(19(15)24)30-36(5,33)34/h6-9,11-13,30H,10H2,1-5H3,(H,27,32)(H,25,26,28)/t13-/m0/s1
  InChIKey: CMJCXYNUCSMDBY-ZDUSSCGKSA-N
• Cross-matching ID:
  PubChem CID: 50922675
  ChEBI ID: CHEMBL3301612
  CAS Number: 1269440-17-6
  UNII: 8L7891MRB6
  DrugBank ID: DB11718
  TTD ID: D0TK7R
  INTEDE ID: DR0578
  ACDINA ID: D01046
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug Pharmacogenomic Perturbation (DPP)NEW: Click to Jump to the Detailed DPP Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Melanoma
• ICD Disease Classification: 2C30

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serine/threonine-protein kinase B-raf (BRAF)	DTT	BRAF	3.00E-01	0.1	0.2
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	9.10E-03	5.38E-02	2.83E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.75E-01	3.78E-02	1.44E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from LGX818 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of LGX818 and Ivosidenib.	Acute myeloid leukaemia [2A60]	[4]
Arn-509	DMT81LZ	Major	Increased metabolism of LGX818 caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[5]
Levalbuterol	DM5YBO1	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Levalbuterol.	Asthma [CA23]	[6]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of LGX818 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[5]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of LGX818 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[5]
LY2835219	DM93VBZ	Moderate	Increased metabolism of LGX818 caused by LY2835219 mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[5]
PF-04449913	DMSB068	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[5]
Osilodrostat	DMIJC9X	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Osilodrostat.	Cushing syndrome [5A70]	[5]
Deutetrabenazine	DMUPFLI	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Deutetrabenazine.	Dystonic disorder [8A02]	[7]
Ingrezza	DMVPLNC	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Ingrezza.	Dystonic disorder [8A02]	[5]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of LGX818 caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[5]
Bay 80-6946	DMLOS5R	Moderate	Increased metabolism of LGX818 caused by Bay 80-6946 mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[5]
Ripretinib	DM958QB	Moderate	Decreased clearance of LGX818 due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[8]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of LGX818 and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[9]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[5]
Berotralstat	DMWA2DZ	Major	Decreased clearance of LGX818 due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[10]
Brigatinib	DM7W94S	Moderate	Increased metabolism of LGX818 caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[5]
PF-06463922	DMKM7EW	Major	Increased metabolism of LGX818 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[5]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of LGX818 and Selpercatinib.	Lung cancer [2C25]	[9]
IPI-145	DMWA24P	Major	Decreased metabolism of LGX818 caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[5]
Ubrogepant	DM749I3	Moderate	Decreased clearance of LGX818 due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[11]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of LGX818 due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[12]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of LGX818 and Ozanimod.	Multiple sclerosis [8A40]	[13]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of LGX818 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[5]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Entrectinib.	Non-small cell lung cancer [2C25]	[8]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Rucaparib.	Ovarian cancer [2C73]	[5]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Triclabendazole.	Parasitic worm infestation [1F90]	[5]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of LGX818 and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[14]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of LGX818 and Lefamulin.	Pneumonia [CA40]	[15]
Relugolix	DMK7IWL	Moderate	Increased risk of prolong QT interval by the combination of LGX818 and Relugolix.	Prostate cancer [2C82]	[9]
Voxelotor	DMCS6M5	Major	Decreased metabolism of LGX818 caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[5]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of LGX818 caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[5]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of LGX818 and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[16]
Elagolix	DMB2C0E	Moderate	Increased metabolism of LGX818 caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[5]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Succinic acid	E00044	1110	Buffering agent
Crospovidone	E00626	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Gelatin	E00630	Not Available	Other agent
Magnesium stearate	E00208	11177	lubricant
Poloxamer 188	E00645	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Copovidone	E00693	Not Available	Film/membrane-forming agent; Modified-release agent; Binding agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Encorafenib 75 mg capsule	75 mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] Development of encorafenib for BRAF-mutated advanced melanoma. Curr Opin Oncol. 2018 Mar;30(2):125-133.
• [4] Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
• [5] Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
• [6] Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
• [7] Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
• [8] Cerner Multum, Inc. "Australian Product Information.".
• [9] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [10] Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
• [11] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [12] Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
• [13] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [14] Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
• [15] Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
• [16] Canadian Pharmacists Association.