Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMNQXV8)

• Drug Name: LGX818 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 50922675
  CAS Number: CAS 1269440-17-6
  TTD Drug ID: DMNQXV8
  INTEDE Drug ID: DR0578
  ACDINA Drug ID: D01046

Molecule-Related Drug Atlas

Drug(s) Targeting Serine/threonine-protein kinase B-raf (BRAF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dabrafenib	DMX6OE3	Melanoma	2C30	Approved	[4]
Vemurafenib	DM62UG5	Melanoma	2C30	Approved	[5]
PLX8394	DMRTD7I	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
CEP-32496	DMAO04B	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[7]
BGB-283	DMVYTG7	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
ARQ 736	DMP9ZT1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
RO-5212054	DML4C3Q	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
ASN003	DMJCX6D	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
BMS-908662	DM3K8VM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
ABM-1310	DMS1HR3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[23]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[24]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[25]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[26]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[27]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[28]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[29]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[30]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[31]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[32]

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]

References

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• [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] Clinical pipeline report, company report or official report of GlaxoSmithKline (2011).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell Melanoma Res. 2014 Mar;27(2):253-62.
• [7] Clinical pipeline report, company report or official report of Ambit Biosciences.
• [8] BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther. 2015 Oct;14(10):2187-97.
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• [10] National Cancer Institute Drug Dictionary (drug id 680347).
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• [12] Clinical pipeline report, company report or official report of Exelixis (2011).
• [13] Clinical pipeline report, company report or official report of ABM Therapeutics.
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• [18] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [19] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [22] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [23] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [24] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [25] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [26] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [27] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [28] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [29] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [30] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [31] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [32] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.