生物活性

• 描述MLN2480 is a brain-penetrant pan-RAF kinase inhibitor with IC50 values of 190nM and 248nM for KIAA1549:BRAF fusion or the BRAF^V600E, respectively, exhibiting antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models. Treatment with MLN2480 led to a dose-dependent decrease of p-ERK in murine p53^-/- neuroprogenitor cells expressed KIAA1549:BRAF fusion or the BRAF^V600E at dose ranging in 30-1000nM and wide-type BRAF at dose ranging in 1000-3000nM. MLN2480 at concentration at 1μM led to decreased level of p-MEK1 and p-ERK in both murine p53^-/- neuroprogenitor cells expressed KIAA1549:BRAF fusion and the BRAF^V600E, but not with T529N mutant which blocks drug binding. MLN2480 exhibited the ability to cross the blood–brain barrier and retard growth of BRAF^V600E and KIAA1549:BRAF intracranial tumors in NCr-NU mice oral dose with 30mg/kg MLN2480, BID.

• 动物研究
  剂量	Mice: 12.5 mg/kg[2] (p.o.), 30 mg/kg[3] (p.o.)
  给药途径	p.o.

• 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
  NCT02723006	Melanoma	Phase 1	Terminated(Business decision P... more >>rotocol efficacy futility met) Collapse <<	-	United States, Arizona ... more >> University of Arizona Cancer Center Tucson, Arizona, United States United States, California University of California Los Angeles - Jonsson Comprehensive Cancer Center Los Angeles, California, United States University of California San Francisco Medical Center San Francisco, California, United States United States, Colorado University of Colorado Cancer Center Aurora, Colorado, United States United States, Georgia Emory University Hospital Atlanta, Georgia, United States United States, Massachusetts Dana-Farber Cancer Institute Boston, Massachusetts, United States Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States United States, Minnesota Virginia Piper Cancer Institute Minneapolis, Minnesota, United States United States, Missouri Washington University School of Medicine Saint Louis, Missouri, United States United States, New York New York University Langone Medical Center New York, New York, United States United States, Pennsylvania Saint Luke's Cancer Center - Bethlehem Easton, Pennsylvania, United States Fox Chase Cancer Center Philadelphia, Pennsylvania, United States United States, Texas Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas, Texas, United States United States, Virginia Inova Fairfax Hospital Fairfax, Virginia, United States Collapse <<
  NCT02327169	Advanced Nonhematologic Malign... more >>ancies Collapse <<	Phase 1	Completed	-	United States, Massachusetts ... more >> Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 2114 Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 2115 Dana Farber Cancer Institute Boston, Massachusetts, United States, 2115 United States, Pennsylvania Fox Chase Cancer Center Philadelphia, Pennsylvania, United States, 19111 United States, Texas The University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030 France Institut Bergonie Bordeaux cedex, Gironde, France, 33076 Institut Claudius Regaud-Oncopole Toulouse cedex 09, Haute Garonne, France, 31059 Institut Gustave Roussy Villejuif cedex, Val De Marne, France, 94805 Spain Hospital Universitari Vall d'Hebron Barcelona, Spain, 8035 START Madrid. Fundacion Jimenez Diaz Madrid, Spain, 28040 Hospital Clinico Universitario Virgen de la Victoria Malaga, Spain, 29010 United Kingdom Sarah Cannon Research Institure UK London, Greater London, United Kingdom, W1G 6AD The Chrisie Manchester, Greater Manchester, United Kingdom, M20 4BX Churchill Hospital Oxford, Oxfordshire, United Kingdom, OX3 7LJ Collapse <<
  NCT01425008	Melanoma Meta... more >>static Melanoma Solid Tumor Collapse <<	Phase 1	Completed	-	United States, California ... more >> San Francisco, California, United States United States, Colorado Denver, Colorado, United States United States, Georgia Augusta, Georgia, United States United States, Indiana Indianapolis, Indiana, United States United States, New York New York, New York, United States United States, Pennsylvania Easton, Pennsylvania, United States Philadelphia, Pennsylvania, United States United States, Texas San Antonio, Texas, United States United States, Washington Lakewood, Washington, United States United Kingdom Bristol, Avon, United Kingdom Cambridge, Cambridgeshire, United Kingdom Chelmsford, Essex, United Kingdom London, Greater London, United Kingdom Manchester, Greater Manchester, United Kingdom Oxford, Oxfordshire, United Kingdom Newcastle upon Tyne, Tyne & Wear, United Kingdom Collapse <<

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