Encorafenib

Summary

Encorafenib (CHEMBL3301612) is an approved small molecule (ATC L01EC03); indicated across 17 conditions including melanoma and neoplasm; with CIViC clinical evidence for 9 variant-indication associations (e.g. BRAF V600 in melanoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EC03
• Indications: 17 conditions
• Clinical trials: 83
• Precision-oncology evidence (CIViC): 9 variant–indication associations
• Chemistry: 540 Da · C22H27ClFN7O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3301612
Name	Encorafenib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	50922675
ATC	L01EC03
Molecular formula	C22H27ClFN7O4S
Molecular weight	540
InChIKey	CMJCXYNUCSMDBY-ZDUSSCGKSA-N

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

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

Also known as: Braftovi, Encorafenib, Lgx-818, Lgx818, NVP-LGX818, ENCORAFENIB, US9314464, 9, LGX818, Encorafenib (LGX818), encorafenib

Patent coverage: 1,955 distinct patent families (4,624 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,417 (96%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 30 (assay-derived). Sample: Receptor-interacting serine/threonine-protein kinase 3, 5-hydroxytryptamine receptor 2B, Equilibrative nucleoside transporter 1, MAP kinase-activated protein kinase 2, Mitogen-activated protein kinase 8, Kappa-type opioid receptor, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, Muscarinic acetylcholine receptor M3, Mitogen-activated protein kinase 14, Glycogen synthase kinase-3 beta.

Bioactivity

ChEMBL activities: 31 potent at pChembl ≥ 5 of 39 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BRAF	9.52	IC50	0.3	nM	CHEMBL_ACT_16888341
BRAF	9.52	IC50	0.3	nM	CHEMBL_ACT_17761535
BRAF	9.52	IC50	0.3	nM	CHEMBL_ACT_18810769
BRAF	9.52	IC50	0.3	nM	CHEMBL_ACT_27014672
BRAF	9.52	IC50	0.3	nM	CHEMBL_ACT_27014738
BRAF	9.52	IC50	0.3	nM	CHEMBL_ACT_27910940
BRAF	8.7	IC50	2	nM	CHEMBL_ACT_16888372
BRAF	8.4	IC50	4	nM	CHEMBL_ACT_20682886
BRAF	8.4	IC50	4	nM	CHEMBL_ACT_22929312
LIMK1	7.58	Kd	26	nM	CHEMBL_ACT_17909671
PCYT1A	7.39	Kd	41	nM	CHEMBL_ACT_17924344
LIMK2	7.02	Kd	96	nM	CHEMBL_ACT_17909956
CDK4	6.95	Kd	112	nM	CHEMBL_ACT_17890273
BRAF	6.91	Kd	124	nM	CHEMBL_ACT_17885860
PGRMC1	6.69	Kd	204	nM	CHEMBL_ACT_17925647
IRAK1	6.61	Kd	247	nM	CHEMBL_ACT_17908072
RIPK2	6.49	Kd	323	nM	CHEMBL_ACT_17935462
GSK3B	6.37	Kd	425	nM	CHEMBL_ACT_17905271
NLK	6.13	Kd	732	nM	CHEMBL_ACT_17922025
MAP3K20	6.11	Kd	785	nM	CHEMBL_ACT_17948634
MAP3K11	6.09	Kd	812	nM	CHEMBL_ACT_17912049
MAPK9	6.04	Kd	915	nM	CHEMBL_ACT_17916432
RIPK3	6.01	Kd	967	nM	CHEMBL_ACT_17935737
MAP3K4	5.84	Kd	1437	nM	CHEMBL_ACT_17912722
MAPK8	5.73	Kd	1865	nM	CHEMBL_ACT_17916167
MAPK14	5.66	IC50	2200	nM	CHEMBL_ACT_16888402
CSNK1A1	5.48	Kd	3334	nM	CHEMBL_ACT_17893425
TAOK3	5.48	Kd	3325	nM	CHEMBL_ACT_17943509
PDE4D	5.36	AC50	4404	nM	CHEMBL_ACT_25185146
GSK3A	5.28	Kd	5259	nM	CHEMBL_ACT_17905068

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

17 indications (8 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
melanoma	4	MONDO:0005105	EFO:0000756
neoplasm	4	MONDO:0005070	EFO:0000616
metastatic melanoma	4	MONDO:0005191	EFO:0002617
colorectal adenocarcinoma	4	MONDO:0005008	EFO:0000365
cutaneous melanoma	4	MONDO:0005012	EFO:0000389
colorectal neoplasm	4	MONDO:0005335	EFO:0004142
biliary tract neoplasm	3	MONDO:0005304	EFO:0003891
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
thyroid gland carcinoma	2	MONDO:0015075	EFO:0002892
hairy cell leukemia	2	MONDO:0018935	EFO:1000956
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
colon adenocarcinoma	2	MONDO:0002271	EFO:1001949
pancreatic ductal adenocarcinoma	1	MONDO:0005184	MONDO:0005184
skin carcinoma	0	MONDO:0002656	EFO:0009259

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 83.

Phase distribution

Phase	Trials
PHASE2	40
PHASE1	13
PHASE1/PHASE2	11
PHASE3	7
Not specified	6
EARLY_PHASE1	3
PHASE4	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05203172	PHASE4	RECRUITING	The FLOTILLA Study: Providing Continued Access to The Study Medicines Encorafenib and Binimetinib for Participants in Prior Clinical Trials
NCT07092410	PHASE4	WITHDRAWN	Surgical or Radiotherapeutic Intervention Concerning Large Singular Stable to Progressive Metastases in Patients With BRAFV600-mutated Melanoma Receiving Treatment With Encorafenib + Binimetinib
NCT03803553	PHASE3	RECRUITING	Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer
NCT04607421	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
NCT04657991	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma
NCT05270044	PHASE3	ACTIVE_NOT_RECRUITING	Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.
NCT05615818	PHASE3	RECRUITING	Personalized Medicine for Advanced Biliary Cancer Patients
NCT05710406	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer
NCT01909453	PHASE3	COMPLETED	Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
NCT02928224	PHASE3	COMPLETED	Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer
NCT02910700	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma
NCT03235245	PHASE2	ACTIVE_NOT_RECRUITING	Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib
NCT03563729	PHASE2	RECRUITING	Melanoma Metastasized to the Brain and Steroids
NCT03839342	PHASE2	ACTIVE_NOT_RECRUITING	Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations
NCT04017650	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Encorafenib, Cetuximab, and Nivolumab in Treating Patients With Microsatellite Stable, BRAFV600E Mutated Unresectable or Metastatic Colorectal Cancer
NCT04061980	PHASE2	ACTIVE_NOT_RECRUITING	Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer
NCT04074096	PHASE2	ACTIVE_NOT_RECRUITING	Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis
NCT04324112	PHASE2	RECRUITING	Encorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL
NCT04511013	PHASE2	RECRUITING	A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
NCT04526782	PHASE2	ACTIVE_NOT_RECRUITING	ENCOrafenib With Binimetinib in bRAF NSCLC
NCT05026983	PHASE2	RECRUITING	Binimetinib and Encorafenib for the Treatment of Metastatic Melanoma and Central Nervous System Metastases
NCT05195632	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Study Investigating the Combination of Encorafenib and Binimetinib in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung Cancer
NCT05217446	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer
NCT05308446	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation
NCT05725200	PHASE2	RECRUITING	Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer
NCT06194929	PHASE1/PHASE2	RECRUITING	Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma
NCT06411600	PHASE2	RECRUITING	Combination Therapy for BRAF-V600E Metastatic CRCm
NCT06578559	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Study of ctDNA-guided Encorafenib Plus Cetuximab Retreatment in Patients BRAF V600E Mutated mCRC
NCT06640166	PHASE2	RECRUITING	Encorafenib + Cetuximab Beyond Progression in Combination With FOLFIRI in Patients With BRAF V600E Mutated Metastatic Colorectal Cancer Progressing on Encorafenib + Cetuximab.
NCT06887088	PHASE2	RECRUITING	Encorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases
NCT07178717	PHASE2	NOT_YET_RECRUITING	A Study to Characterize Encorafenib Plus Cetuximab as Rechallenge Treatment for BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy With BRAF Inhibitors-based Combinations
NCT01543698	PHASE1/PHASE2	COMPLETED	A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
NCT01719380	PHASE2	COMPLETED	Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer
NCT01777776	PHASE1/PHASE2	TERMINATED	Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.
NCT01820364	PHASE2	TERMINATED	LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma
NCT01894672	PHASE2	COMPLETED	BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation
NCT01981187	PHASE2	TERMINATED	LGX818 for Patients With BRAFV600 Mutated Tumors
NCT02109653	PHASE2	WITHDRAWN	Efficacy and Safety of LGX818 in Patients With Advanced or Metastatic BRAF V600 Mutant NSCLC
NCT02159066	PHASE2	COMPLETED	LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma
NCT02278133	PHASE1/PHASE2	COMPLETED	Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations

Clinical evidence (CIViC)

Variant × indication × effect (9 predictive associations from 9 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
BRAF V600	Melanoma	Sensitivity/Response	Encorafenib + Binimetinib	CIViC A	EID7287
BRAF V600E	Colorectal Cancer	Sensitivity/Response	Cetuximab + Encorafenib	CIViC A	EID9851
BRAF V600	Colorectal Cancer	Sensitivity/Response	Encorafenib + Cetuximab	CIViC B	EID6046
BRAF V600	Colorectal Cancer	Sensitivity/Response	Cetuximab + Encorafenib + Alpelisib	CIViC B	EID6047
BRAF V600E	Colorectal Cancer	Sensitivity/Response	Cetuximab + Nivolumab + Encorafenib	CIViC B	EID12624
BRAF V600E	Colorectal Cancer	Sensitivity/Response	Encorafenib + Binimetinib + Cetuximab	CIViC B	EID7260
BRAF V600E	Colorectal Cancer	Sensitivity/Response	Encorafenib + Cetuximab + Binimetinib	CIViC B	EID7612
KRAS Amplification	Colorectal Cancer	Resistance	Cetuximab + Encorafenib	CIViC B	EID2928
BRAF V600E	Colorectal Cancer	Sensitivity/Response	Panitumumab + Encorafenib	CIViC C	EID11309

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).