| 词条 | Encorafenib |
| 释义 |
| IUPAC_name = Methyl [(2S)-1- | image = LGX818 structure.svg | width = 240px | image2 = | width2 = | tradename =Braftovi | CAS_number =1269440-17-6 | CAS_supplemental = | ATC_prefix = L01 | ATC_suffix = XE46 | ATC_supplemental = | PubChem = 50922675 | DrugBank = DB11718 | KEGG = D11053 | ChemSpiderID = 28536139 | C=22 | H=27 | Cl=1 | F=1 | N=7 | O=4 | S=1 | molecular_weight = 540.011 g/mol | SMILES = C[C@@H](CNc1nccc(n1)c2cn(nc2c3cc(cc(c3F)NS(=O)(=O)C)Cl)C(C)C)NC(=O)OC | StdInChI = 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 | StdInChIKey = CMJCXYNUCSMDBY-ZDUSSCGKSA-N | synonyms = LGX818 | density = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | specific_rotation = | sec_combustion = | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | licence_EU = | licence_US = | DailyMedID = | pregnancy_AU = | pregnancy_US = | pregnancy_category= | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = Approved | dependency_liability = | routes_of_administration = |alt=|caption=|type=|MedlinePlus=|UNII=8L7891MRB6|ChEMBL=CHEMBL3301612}}Encorafenib (trade name Braftovi) is a drug for the treatment of certain melanomas. It is a small molecule BRAF inhibitor [1] that targets key enzymes in the MAPK signaling pathway. This pathway occurs in many different cancers including melanoma and colorectal cancers.[2] The substance was being developed by Novartis and then by Array BioPharma. In June 2018 it was approved by the FDA in combination with binimetinib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.[3] PharmacologyEncorafenib acts as an ATP-competitive RAF kinase inhibitor, decreasing ERK phosphorylation and down-regulation of CyclinD1.[4] This arrests the cell cycle in G1 phase, inducing senescence without apoptosis.[4] Therefore it is only effective in melanomas with a BRAF mutation, which make up 50% of all melanomas.[5] The plasma elimination half-life of encorafenib is approximately 6 hours, occurring mainly through metabolism via cytochrome P450 enzymes.[6] Clinical trialsSeveral clinical trials of LGX818, either alone or in combinations with the MEK inhibitor MEK162,[7] are being run. As a result of a successful Phase Ib/II trials, Phase III trials are currently being initiated.[8] References1. ^{{cite journal | vauthors = Koelblinger P, Thuerigen O, Dummer R | title = Development of encorafenib for BRAF-mutated advanced melanoma | journal = Current Opinion in Oncology | volume = 30 | issue = 2 | pages = 125–133 | date = March 2018 | pmid = 29356698 | pmc = 5815646 | doi = 10.1097/CCO.0000000000000426 }} {{Extracellular chemotherapeutic agents}}2. ^{{cite journal | vauthors = Burotto M, Chiou VL, Lee JM, Kohn EC | title = The MAPK pathway across different malignancies: a new perspective | journal = Cancer | volume = 120 | issue = 22 | pages = 3446–56 | date = November 2014 | pmid = 24948110 | pmc = 4221543 | doi = 10.1002/cncr.28864 }} 3. ^{{Cite web|url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm611981.htm|title=Approved Drugs - FDA approves encorafenib and binimetinib in combination for unresectable or metastatic melanoma with BRAF mutations|last=Research|first=Center for Drug Evaluation and|website=www.fda.gov |access-date=2018-06-28}} 4. ^1 {{cite journal | vauthors = Li Z, Jiang K, Zhu X, Lin G, Song F, Zhao Y, Piao Y, Liu J, Cheng W, Bi X, Gong P, Song Z, Meng S | title = Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells | journal = Cancer Letters | volume = 370 | issue = 2 | pages = 332–44 | date = January 2016 | pmid = 26586345 | doi = 10.1016/j.canlet.2015.11.015 }} 5. ^{{cite journal | vauthors = Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, Dicara D, Ramos AH, Lawrence MS, Cibulskis K, Sivachenko A, Voet D, Saksena G, Stransky N, Onofrio RC, Winckler W, Ardlie K, Wagle N, Wargo J, Chong K, Morton DL, Stemke-Hale K, Chen G, Noble M, Meyerson M, Ladbury JE, Davies MA, Gershenwald JE, Wagner SN, Hoon DS, Schadendorf D, Lander ES, Gabriel SB, Getz G, Garraway LA, Chin L | display-authors = 6 | title = A landscape of driver mutations in melanoma | journal = Cell | volume = 150 | issue = 2 | pages = 251–63 | date = July 2012 | pmid = 22817889 | pmc = 3600117 | doi = 10.1016/j.cell.2012.06.024 }} 6. ^{{cite journal | vauthors = Koelblinger P, Thuerigen O, Dummer R | title = Development of encorafenib for BRAF-mutated advanced melanoma | journal = Current Opinion in Oncology | volume = 30 | issue = 2 | pages = 125–133 | date = March 2018 | pmid = 29356698 | pmc = 5815646 | doi = 10.1097/CCO.0000000000000426 }} 7. ^{{cite web | url = https://clinicaltrials.gov/ct2/results?cond=&term=LGX818&cntry=&state=&city=&dist= | title = 18 Studies found for: LGX818 | work = Clinicaltrials.gove }} 8. ^{{ClinicalTrialsGov|NCT01909453|Study Comparing Combination of LGX818 Plus MEK162 and LGX818 Monotherapy Versus Vemurafenib in BRAF Mutant Melanoma (COLUMBUS)}} 2 : Cancer treatments|B-Raf inhibitor |
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