生物活性

• 描述Farnesylation is a posttranslational modification of proteins by which an isoprenyl group is added to a cysteine residue. In mammalian cells, newly synthesized proteins like Ras must be posttranslationally modified by farnesylation through farnesyl protein transferase to allow its proper membrane localization. Tipifarnib is a potent and selective farnesyl protein transferase (FPT) inhibitor with IC50 values of 0.86 nM and 7.9 nM for inhibition of the farnesylation of lamin B and K-RasB peptide substrates, respectively. Treatment with Tipifarnib at concentration ranging in 5-50nM for 3 days inhibited Ras (p21ras) processing in intact NIH 3T3 cells stably transfected with the T24 H-ras oncogene cells, observed by ratio of soluble and total particulate fractions. Tipifarnib exhibited a panel of human tumor cell lines of various tissue types with wide-type ras gene with IC50 values ranging in 2.7-111nM. Oral administration of Tipifarnib at dose ranging in 6.25–100 mg/kg, b.i.d, dose-dependently inhibited the growth of tumors bearing mutant H-ras, mutant K-ras, and wild-type ras genes in nude mice bearing s.c. tumors.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  human 786-0 cell	-	Growth inhibition assay	-	Inhibition of human 786-0 cell growth in a cell viability assay, IC50=0.32173 μM	SANGER
  human 8505C cell	-	Growth inhibition assay	-	Inhibition of human 8505C cell growth in a cell viability assay, IC50=0.43109 μM	SANGER
  human A375 cell	-	Growth inhibition assay	-	Inhibition of human A375 cell growth in a cell viability assay, IC50=0.61648 μM	SANGER

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• 动物研究
  剂量	Mice: 3 mg/kg[3] (s.c.); 10 mg/kg[4] (i.p.); 100 mg/kg[5] (p.o.)
  给药途径	s.c., i.p., 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
  NCT00076102	Neurofibromatosis 1 ... more >> Neurofibroma, Plexiform Collapse <<	Phase 2	Completed	-	United States, Alabama ... more >> University of Alabama Birmingham, Alabama, United States, 35233 United States, District of Columbia Childrens National Medical Center Washington, District of Columbia, United States, 20010 United States, Illinois Childrens Memorial Hospital, Chicago Chicago, Illinois, United States, 60614 United States, Maryland Johns Hopkins Oncology Center Baltimore, Maryland, United States, 21287 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland, United States, 20892 United States, Massachusetts Childrens Hospital, Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, Minnesota Mayo Clinic, Rochester Rochester, Minnesota, United States, 55905 United States, Missouri St. Louis Children's Hospital Saint Louis, Missouri, United States, 63110 United States, New York Beth Israel Medical Center New York, New York, United States, 10003 SUNY Upstate Medical University Syracuse, New York, United States, 13210 United States, Ohio Cleveland Clinic Cleveland, Ohio, United States, 44195 United States, Oregon Oregon Health Sciences University Portland, Oregon, United States, 97201-3098 United States, Pennsylvania Childrens Hospital, Philadelphia Philadelphia, Pennsylvania, United States, 19104 Childrens Hospital, Pittsburgh Pittsburgh, Pennsylvania, United States, 15213 United States, Texas Texas Children's Hospital Houston, Texas, United States, 77030 Collapse <<
  NCT00076102	-	-	Completed	-	-
  NCT02845232	-	-	Completed	-	France ... more >> Hospices Civils de Lyon - Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet Pierre-benite, France, 69310 Collapse <<

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