生物活性

• 靶点	B-Raf (V600E) IC50:0.3nM

• 描述The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. Among them, B-RAF is the most frequently mutated protein kinase in human cancers. Encorafenib is a potent and selective B-Raf^V600E inhibitor, with no significant activity observed against a panel of 100 kinases (IC50>900nM). Encorafenib suppressed p-ERK with EC50 value of 3nM as well as led to potent inhibition of proliferation with EC50 value of 4nM in A375 cells (B-Raf^V600E), and did not inhibit proliferation of >400 cell lines expressing wild-type BRAF. Encorafenib showed good pharmacodynamics as single dose at 6mg/kg resulting in strong (75%) and sustained (>24h) decrease in p-MEK in PK/PD studies. Consistent with the in vitro data, Encorafenib can induce tumor regression in multiple BRAF mutant human tumor xenograft models grown in immune compromised mice and rats at doses as low as 1mg/kg, but inactive against BRAF wild-type tumors at doses up to 300 mg/kg bid^[1].

• 动物研究
  剂量	Mice: 0.6 mg/kg - 300 mg/kg[2] (p.o.) Rat: 5 mg/kg[3] (i.v.), 50 mg/kg[3] (p.o.)
  给药途径	p.o., i.v.
  动物药代数据	Animal Rats[3] Dose 5 mg/kg (i.v.) 50 mg/kg (p.o.) Administration i.v. p.o. AUCinf 58900 h·ng/ml (i.v.) 245000 h·ng/ml (p.o.) T1/2 62 h (i.v.) 7.6 h (p.o.) Tmax 0.083 h (i.v.) 2 - 4 h (p.o.) Cmax 43500 ng/ml (i.v.) 36400 ng/ml (p.o.) Protein binding (free drug %) 96.4% - 99%

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01519427	-	-	Terminated(Study terminated du... more >>e to slow accrual) Collapse <<	-	-
  NCT01519427	Recurrent Melanoma ... more >> Stage IIIA Melanoma Stage IIIB Melanoma Stage IIIC Melanoma Stage IV Melanoma Collapse <<	Phase 2	Terminated(Study terminated du... more >>e to slow accrual) Collapse <<	-	United States, Georgia ... more >> Emory University Atlanta, Georgia, United States, 30322 United States, New Jersey Cancer Institute of New Jersey New Brunswick, New Jersey, United States, 08903 United States, Tennessee Vanderbilt-Ingram Cancer Center Nashville, Tennessee, United States, 37232 United States, Virginia Virginia Commonwealth University/Massey Cancer Center Richmond, Virginia, United States, 23298 Collapse <<
  NCT02631447	Metastatic Melanoma	Phase 2	Recruiting	December 2021	Austria ... more >> Medical University of Vienna Not yet recruiting Wien, Austria, 1090 Contact: Christoph Hoeller, MD          Principal Investigator: Christoph Hoeller, MD          France APHM Hopital de la Timone Not yet recruiting Marseille, France, 13005 Contact: Jean Jacques Grob, MD          Principal Investigator: Jean Jacques Grob, MD          Hôpitaux Universitaires Saint-Louis Not yet recruiting Paris, France, 75010 Contact: Celeste Lebbè, MD          Principal Investigator: Celeste Lebbè, MD          Institut Gustave Roussy Not yet recruiting Villejuif, France, 94800 Contact: Caroline Robert, MD          Principal Investigator: Caroline Robert, MD          Germany University of Tuebingen Not yet recruiting Tuebingen, Germany, 72074 Contact: Benjamin Weide, MD          Principal Investigator: Benjamin Weide, MD          Greece University of Athens Not yet recruiting Athens, Greece, 11527 Contact: Helen Gogas, MD          Principal Investigator: Helen Gogas, MD          Italy IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori (I.R.S.T) S.r.l. Recruiting Meldola, Forlì-Cesena, Italy, 47014 Contact: Massimo Guidoboni, MD          Principal Investigator: Massimo Guidoboni, MD          National Institute of Cancer Recruiting Bari, Italy, 70124 Contact: Michele Guida, MD          Principal Investigator: Michele Guida, MD          Università degli Studi di Bari Aldo Moro Not yet recruiting Bari, Italy, 70124 Contact: Francesco Silvestris, MD          Principal Investigator: Francesco Silvestris, MD          Azienda Ospedaliera Papa Giovanni XXIII Recruiting Bergamo, Italy, 24127 Contact: Mario Mandalà, MD          Principal Investigator: Mario Mandalà, MD          IRCCS San Martino - IST Recruiting Genova, Italy, 16132 Contact: Paola Queirolo          Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori Recruiting Milano, Italy, 20133 Contact: Michele Del Vecchio, MD          Principal Investigator: Michele Del Vecchio, MD          IEO - Istituto Europeo di Oncologia - IRCCS Recruiting Milano, Italy Contact: Pierfrancesco Ferrucci          Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" Recruiting Naples, Italy, 80131 Contact: Paolo Ascierto, MD          Principal Investigator: Paolo Ascierto, Md          Azienda Ospedaliero Universitaria Federico II Not yet recruiting Naples, Italy Contact: Sabino De Placido          Istituto Oncologico Veneto Recruiting Padova, Italy, 35128 Contact: Vanna Chiarion-sileni, MD          Principal Investigator: Vanna Chiarion-sileni, MD          Istituto Nazionale Tumori Regina Elena Recruiting Roma, Italy, 00144 Contact: Virginia Ferraresi, MD          Principal Investigator: Virginia Ferraresi, MD          Istituto Dermopatico dell'Immacolata - IDI - IRCCS Recruiting Roma, Italy, 00167 Contact: Paolo Marchetti, MD          Contact: A          Principal Investigator: Paolo Marchetti, Md          IRCCS Casa Sollievo della Sofferenza Recruiting San Giovanni Rotondo, Italy Contact: Evaristo Maiello          Azienda Ospedaliera Universitaria - Città della Salute e della Scienza di Torino Not yet recruiting Torino, Italy, 10126 Contact: Maria Teresa Fierro, MD          Principal Investigator: Maria Teresa Fierro, MD          Azienda Ospedaliera Universitaria Integrata di Udine Not yet recruiting Udine, Italy Contact: Alessandro Minisini, MD          Spain Hospital Clínic Barcelona Not yet recruiting Barcelona, Spain, 08036 Contact: Ana Arance, MD          Principal Investigator: Ana Arance, MD          Clinica Universidad de Navarra Not yet recruiting Pamplona, Spain, 31008 Contact: Salvador Algarra, MD          Principal Investigator: Salvador Algarra, MD          Sweden Karolinska University Hospital Not yet recruiting Stockholm, Sweden, S-171 Contact: Johan Hansson, MD          Principal Investigator: Johan Hansson, MD          Switzerland Centre Hospitalier Universitaire Vaudois Not yet recruiting Lausanne, Switzerland Contact: Oliver Michielin          University Hospital Zurich Not yet recruiting Zurich, Switzerland, CH809 Contact: Reinhard Dummer, MD          Principal Investigator: Reinhard Dummer, MD          United Kingdom The Royal Marsden NHS Foundation Trust Not yet recruiting London, United Kingdom, SW36J Contact: James Larkin, MD          Principal Investigator: James Larkin, Md          The Christie NHS Foundation Trust Not yet recruiting Manchester, United Kingdom, M204B Contact: Paul Lorigan, MD          Principal Investigator: Paul Lorigan, MD Collapse <<

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