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encorafenib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
Raf (Rapidely Accelerated Fibrosarcoma) kinase inhibitors	5289	1269440-17-6

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: encorafenib braftovi NVP-LGX818-NXA	Encorafenib is a kinase inhibitor that targets BRAF V600E, as well as wild-type BRAF and CRAF. Mutations in the BRAF gene, such as BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Encorafenib was also able to bind to other kinases in vitro including JNK1, JNK2, JNK3, LIMK1, LIMK2, MEK4, and STK36 and substantially reduce ligand binding to these kinases at clinically achievable concentrations. Encorafenib inhibited in vitro growth of tumor cell lines expressing BRAF V600 E, D, and K mutations. In mice implanted with tumor cells expressing BRAF V600E, encorafenib induced tumor regressions associated with RAF/MEK/ERK pathway suppression. Molecular weight: 540.01 Formula: C22H27ClFN7O4S CLOGP: 2.88 LIPINSKI: 2 HAC: 11 HDO: 3 TPSA: 140.13 ALOGS: -4.68 ROTB: 9 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

encorafenib
braftovi
NVP-LGX818-NXA

Encorafenib is a kinase inhibitor that targets BRAF V600E, as well as wild-type BRAF and CRAF. Mutations in the BRAF gene, such as BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Encorafenib was also able to bind to other kinases in vitro including JNK1, JNK2, JNK3, LIMK1, LIMK2, MEK4, and STK36 and substantially reduce ligand binding to these kinases at clinically achievable concentrations. Encorafenib inhibited in vitro growth of tumor cell lines expressing BRAF V600 E, D, and K mutations. In mice implanted with tumor cells expressing BRAF V600E, encorafenib induced tumor regressions associated with RAF/MEK/ERK pathway suppression.

Molecular weight: 540.01
Formula: C22H27ClFN7O4S
CLOGP: 2.88
LIPINSKI: 2
HAC: 11
HDO: 3
TPSA: 140.13
ALOGS: -4.68
ROTB: 9

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.45	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
June 27, 2018	FDA	ARRAY BIOPHARMA INC
Jan. 8, 2019	PMDA	Ono Pharmaceutical Co., Ltd.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Serous retinal detachment	550.53	30.64	75	3060	292	63485595
Neoplasm progression	181.51	30.64	68	3067	36360	63449527
Serous retinopathy	118.33	30.64	15	3120	27	63485860
Death	93.57	30.64	103	3032	374278	63111609
Retinal detachment	77.59	30.64	23	3112	5946	63479941
Second primary malignancy	75.19	30.64	24	3111	7929	63477958
Off label use	69.66	30.64	121	3014	674341	62811546
Pyrexia	64.30	30.64	96	3039	470382	63015505
Colitis	64.12	30.64	36	3099	48492	63437395
Macular detachment	58.24	30.64	9	3126	95	63485792
Hepatic function abnormal	47.55	30.64	27	3108	37115	63448772
Uveitis	43.30	30.64	18	3117	12535	63473352
Hospice care	40.11	30.64	15	3120	7917	63477970
Diarrhoea	40.07	30.64	100	3035	715266	62770621
Dermatitis acneiform	38.81	30.64	13	3122	4983	63480904
Disease progression	37.98	30.64	38	3097	122720	63363167
Decreased appetite	36.66	30.64	53	3082	250999	63234888
Nausea	34.50	30.64	106	3029	854365	62631522
Intestinal obstruction	33.05	30.64	20	3115	30879	63455008
Large intestinal ulcer	30.93	30.64	10	3125	3434	63482453

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Serous retinal detachment	499.11	27.21	80	3244	532	34953075
Neoplasm progression	265.57	27.21	95	3229	23205	34930402
Serous retinopathy	122.48	27.21	19	3305	98	34953509
Second primary malignancy	63.51	27.21	25	3299	7861	34945746
Death	53.85	27.21	117	3207	397932	34555675
Nausea	44.82	27.21	99	3225	339809	34613798
Disease progression	44.49	27.21	53	3271	108024	34845583
Blood creatine phosphokinase increased	43.08	27.21	35	3289	44822	34908785
Dermatitis acneiform	40.81	27.21	17	3307	6172	34947435
Vision blurred	36.19	27.21	32	3292	45931	34907676
Pyrexia	34.10	27.21	88	3236	332925	34620682
Off label use	32.35	27.21	100	3224	419424	34534183
Subretinal fluid	29.38	27.21	7	3317	403	34953204

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Serous retinal detachment	1017.06	26.31	155	6142	879	79737212
Neoplasm progression	407.34	26.31	153	6144	51529	79686562
Serous retinopathy	234.41	26.31	34	6263	127	79737964
Death	149.25	26.31	202	6095	566312	79171779
Second primary malignancy	125.66	26.31	46	6251	14304	79723787
Off label use	92.35	26.31	213	6084	907002	78831089
Retinal detachment	82.27	26.31	30	6267	9217	79728874
Pyrexia	80.93	26.31	170	6127	678539	79059552
Dermatitis acneiform	80.00	26.31	30	6267	9963	79728128
Blood creatine phosphokinase increased	68.37	26.31	50	6247	66040	79672051
Uveitis	68.04	26.31	31	6266	16799	79721292
Macular detachment	66.11	26.31	12	6285	215	79737876
Colitis	63.75	26.31	50	6247	73257	79664834
Vision blurred	62.89	26.31	58	6239	105840	79632251
Nausea	62.72	26.31	191	6106	957005	78781086
Hepatic function abnormal	57.47	26.31	47	6250	73060	79665031
Disease progression	56.31	26.31	71	6226	184291	79553800
Diarrhoea	55.09	26.31	173	6124	880316	78857775
Hospice care	51.35	26.31	22	6275	10302	79727789
Decreased appetite	49.27	26.31	93	6204	342325	79395766
Retinopathy	43.65	26.31	15	6282	3876	79734215
Liver disorder	36.03	26.31	36	6261	72381	79665710
Subretinal fluid	35.35	26.31	9	6288	823	79737268
Amylase increased	34.15	26.31	17	6280	11192	79726899
Large intestinal ulcer	33.36	26.31	13	6284	4784	79733307
Lipase increased	33.28	26.31	19	6278	16447	79721644
Demyelinating polyneuropathy	33.10	26.31	10	6287	1716	79736375
Macular oedema	31.69	26.31	13	6284	5461	79732630
Hepatic cytolysis	31.40	26.31	22	6275	27129	79710962
Detachment of retinal pigment epithelium	30.64	26.31	8	6289	808	79737283
Underdose	29.63	26.31	23	6274	33128	79704963
Retinal oedema	29.31	26.31	8	6289	957	79737134
Paronychia	27.26	26.31	13	6284	7795	79730296

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EC03	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS B-Raf serine-threonine kinase (BRAF) inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID
Metastatic malignant melanoma	indication	443493003
Unresectable malignant melanoma with BRAF gene mutation	indication	830150003
BRAF mutation-positive colorectal cancer	indication

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.37	acidic
pKa2	13.42	acidic
pKa3	3.69	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	8541575	Feb. 26, 2030	TREATMENT OF MELANOMA
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	8541575	Feb. 26, 2030	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	8541575	Feb. 26, 2030	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	8541575	Feb. 26, 2030	TREATMENT OF MELANOMA
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	10005761	Aug. 27, 2030	TREATMENT OF MELANOMA
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	9850229	Aug. 27, 2030	INDICATED IN COMBINATION WITH BINIMETINIB FOR THE TREATMENT OF MELANOMA WITH A BRAF MUTATION
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	9850230	Aug. 27, 2030	TREATMENT OF MELANOMA WITH A BRAF MUTATION
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	10005761	Aug. 27, 2030	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	10005761	Aug. 27, 2030	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	10005761	Aug. 27, 2030	TREATMENT OF MELANOMA
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9850229	Aug. 27, 2030	INDICATED IN COMBINATION WITH BINIMETINIB FOR THE TREATMENT OF MELANOMA WITH A BRAF MUTATION
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9850230	Aug. 27, 2030	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9850230	Aug. 27, 2030	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9850230	Aug. 27, 2030	TREATMENT OF MELANOMA WITH A BRAF MUTATION
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	9314464	July 4, 2031	TREATMENT OF MELANOMA MEDIATED BY A B-RAF PROTEIN KINASE
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9314464	July 4, 2031	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA- APPROVED TEST
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9314464	July 4, 2031	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9314464	July 4, 2031	TREATMENT OF MELANOMA MEDIATED BY A B-RAF PROTEIN KINASE
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	9763941	Nov. 21, 2032	TREATMENT OF MELANOMA
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	10258622	Nov. 21, 2032	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9763941	Nov. 21, 2032	TREATMENT OF MELANOMA
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	9474754	Aug. 5, 2033	BRAFTOVI IS A KINASE INHIBITOR INDICATED IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULT PATIENTS WITH METASTATIC COLORECTAL CANCER (CRC) WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	April 8, 2023	ENCORAFENIB, IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULTPATIENTS WITH METASTATIC COLORECTAL CANCER WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	April 8, 2023	ENCORAFENIB, IN COMBINATION WITH CETUXIMAB, FOR THE TREATMENT OF ADULTPATIENTS WITH METASTATIC COLORECTAL CANCER WITH A BRAF V600E MUTATION, AS DETECTED BY AN FDA-APPROVED TEST, AFTER PRIOR THERAPY
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	June 27, 2023	NEW CHEMICAL ENTITY
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	June 27, 2023	NEW CHEMICAL ENTITY
50MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	DISCN	CAPSULE	ORAL	June 27, 2025	ENCORAFENIB IS INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA-APPROVED TEST
75MG	BRAFTOVI	ARRAY BIOPHARMA INC	N210496	June 27, 2018	RX	CAPSULE	ORAL	June 27, 2025	ENCORAFENIB IS INDICATED IN COMBINATION WITH BINIMETINIB, FOR THE TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600E OR V600K MUTATION, AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
RAF proto-oncogene serine/threonine-protein kinase	Kinase	P04049	RAF1_HUMAN	INHIBITOR	IC50	9.52	DRUG LABEL	DRUG LABEL
Serine/threonine-protein kinase B-raf	Kinase	P15056	BRAF_HUMAN	INHIBITOR	IC50	9.33	DRUG LABEL	DRUG LABEL
Mitogen-activated protein kinase 14	Kinase	Q16539	MK14_HUMAN		IC50	5.66	CHEMBL
Mitogen-activated protein kinase kinase kinase 4	Kinase	Q9Y6R4	M3K4_HUMAN		Kd	5.84	CHEMBL
Glycogen synthase kinase-3 beta	Kinase	P49841	GSK3B_HUMAN		Kd	6.37	CHEMBL
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		Kd	6.49	CHEMBL
Mitogen-activated protein kinase 9	Kinase	P45984	MK09_HUMAN		Kd	6.04	CHEMBL
Glycogen synthase kinase-3 alpha	Kinase	P49840	GSK3A_HUMAN		Kd	5.28	CHEMBL
MAP kinase-activated protein kinase 2	Kinase	P49137	MAPK2_HUMAN		Kd	4.83	CHEMBL
Mitogen-activated protein kinase kinase kinase MLT	Kinase	Q9NYL2	MLTK_HUMAN		Kd	6.11	CHEMBL
LIM domain kinase 2	Kinase	P53671	LIMK2_HUMAN		Kd	7.02	CHEMBL
Mitogen-activated protein kinase 8	Kinase	P45983	MK08_HUMAN		Kd	5.73	CHEMBL
Mitogen-activated protein kinase kinase kinase 11	Kinase	Q16584	M3K11_HUMAN		Kd	6.09	CHEMBL
Casein kinase I isoform alpha	Kinase	P48729	KC1A_HUMAN		Kd	5.48	CHEMBL
Cyclin-dependent kinase 4	Kinase	P11802	CDK4_HUMAN		Kd	6.95	CHEMBL
Interleukin-1 receptor-associated kinase 1	Kinase	P51617	IRAK1_HUMAN		Kd	6.61	CHEMBL
Serine/threonine-protein kinase TAO3	Kinase	Q9H2K8	TAOK3_HUMAN		Kd	5.48	CHEMBL
Receptor-interacting serine/threonine-protein kinase 3	Kinase	Q9Y572	RIPK3_HUMAN		Kd	6.01	CHEMBL
Membrane-associated progesterone receptor component 1	Enzyme	O00264	PGRC1_HUMAN		Kd	6.69	CHEMBL
Choline-phosphate cytidylyltransferase A	Enzyme	P49585	PCY1A_HUMAN		Kd	7.39	CHEMBL
Serine/threonine-protein kinase NLK	Kinase	Q9UBE8	NLK_HUMAN		Kd	6.13	CHEMBL
LIM domain kinase 1	Kinase	P53667	LIMK1_HUMAN		Kd	7.58	CHEMBL

External reference:

ID	Source
8L7891MRB6	UNII
C4079208	UMLSCUI
CHEMBL3301612	ChEMBL_ID
50922675	PUBCHEM_CID
DB11718	DRUGBANK_ID
D11053	KEGG_DRUG
9816	INN_ID
7908	IUPHAR_LIGAND_ID
283907	MMSL
34462	MMSL
d08817	MMSL
017615	NDDF
772091004	SNOMEDCT_US
772201002	SNOMEDCT_US
4037644	VANDF
2049106	RXNORM
C000601108	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
BRAFTOVI	HUMAN PRESCRIPTION DRUG LABEL	1	70255-025	CAPSULE	75 mg	ORAL	NDA	32 sections
BRAFTOVI	HUMAN PRESCRIPTION DRUG LABEL	1	70255-025	CAPSULE	75 mg	ORAL	NDA	32 sections
BRAFTOVI	HUMAN PRESCRIPTION DRUG LABEL	1	70255-025	CAPSULE	75 mg	ORAL	NDA	32 sections
BRAFTOVI	HUMAN PRESCRIPTION DRUG LABEL	1	70255-050	CAPSULE	50 mg	ORAL	EXPORT ONLY	1 sections
BRAFTOVI	HUMAN PRESCRIPTION DRUG LABEL	1	70255-050	CAPSULE	50 mg	ORAL	EXPORT ONLY	1 sections