生物活性

• 靶点	HDAC1 IC50:0.57μM

• 描述The histone deacetylase (HDAC) is responsible for the regulation of reversible histone acetylation. CI-994 is an aminophenyl benzamide-type inhibitor of HDAC with IC50 values of 0.9, 0.9, and 1.2 µM for HDAC1, 2, and 3, respectively. It also showed whole-cell HDAC inhibitory activity in 293T cells with an IC50 value of 6 µM and anti-proliferative activity in human cancer cell line HCT116 with an IC50 value of 4 µM^[3]. In non-small cell lung cancer cells, the combination of CI-994 (40 µM) and antineoplastic agents (i.e. 0.01 µM gemcitabine, 0.001 µM docetaxel) caused a marked synergism of action at 48 and 72 h after the treatment^[4]. The administration of CI-994 (10 or 30 mg/kg) for 14 days increased acetylation of histone H3 in mice following spinal cord injury compared to the vehicle-treated group^[5].
• 作用机制CI-994 is an HDAC inhibitor that exerts antitumor effects probably through the inhibition of histone deacetylation and cell cycle arrest^[4].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  293T cells	-	Function assay	-	Inhibition of HDAC in 293T cells, IC50=6 μM	17941625
  human HCT116 cells	-	Cytotoxic assay	-	Cytotoxicity against human HCT116 cells by MTT assay, IC50=4 μM	17941625
  human LNCap	-	Proliferation assay	-	Antiproliferative activity against human LNCap by MTT assay， IC50=7.4 μM	18166465

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• 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
  NCT00004861	Pancreatic Cancer	Phase 2	Completed	-	United States, California ... more >> Cedars-Sinai Comprehensive Cancer Center Los Angeles, California, United States, 90048 United States, Florida H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida, United States, 33612 United States, Maryland Sinai Hospital of Baltimore Baltimore, Maryland, United States, 21225 United States, Michigan William Beaumont Hospital Royal Oak, Michigan, United States, 48073 United States, North Carolina Raleigh Hematology/Oncology Associates - Wake Practice Raleigh, North Carolina, United States, 27609 United States, Ohio Jewish Hospital of Cincinnati, Inc. Cincinnati, Ohio, United States, 45236 Ireland Cancer Center Cleveland, Ohio, United States, 44106-5065 United States, Tennessee West Clinic, P.C. Memphis, Tennessee, United States, 38117 Sarah Cannon-Minnie Pearl Cancer Center Nashville, Tennessee, United States, 37203 United States, Texas Tyler Cancer Center Tyler, Texas, United States, 75702 United States, Virginia Northern Virginia Oncology Group Fairfax, Virginia, United States, 22031 Canada, Manitoba St. Boniface General Hospital Winnipeg, Manitoba, Canada, R2H 2A6 Canada, Nova Scotia Nova Scotia Cancer Centre Halifax, Nova Scotia, Canada, B3H 1V7 Canada, Ontario Cancer Care Ontario-London Regional Cancer Centre London, Ontario, Canada, N6A 4L6 Ottawa Regional Cancer Center - General Division Ottawa, Ontario, Canada, K1H 8L6 Canada, Quebec Centre Hospitalier de l'Universite de Montreal Montreal, Quebec, Canada, H2L-4M1 Collapse <<
  NCT00005093	Lung Cancer	Phase 3	Completed	-	United States, California ... more >> Cedars-Sinai Comprehensive Cancer Center Los Angeles, California, United States, 90048 United States, Florida H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida, United States, 33612 United States, Massachusetts New England Medical Center Hospital Boston, Massachusetts, United States, 02111 United States, Michigan University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan, United States, 48109-0752 Barbara Ann Karmanos Cancer Institute Detroit, Michigan, United States, 48201 United States, North Carolina Raleigh Hematology/Oncology Associates - Wake Practice Raleigh, North Carolina, United States, 27609 United States, Ohio Arthur G. James Cancer Hospital - Ohio State University Columbus, Ohio, United States, 43210 United States, Tennessee West Clinic, P.C. Memphis, Tennessee, United States, 38117 United States, Texas Southwest Regional Cancer Center Austin, Texas, United States, 78705 Canada, Alberta Cross Cancer Institute Edmonton, Alberta, Canada, T6G 1Z2 Canada, British Columbia British Columbia Cancer Agency - Fraser Valley Cancer Centre Surrey, British Columbia, Canada, V3V 1Z2 BC Cancer Agency Vancouver, British Columbia, Canada, V5Z 4E6 British Columbia Cancer Agency - Vancouver Island Cancer Centre Victoria, British Columbia, Canada, V8R 1J8 Canada, Ontario Ottawa Regional Cancer Center - General Division Ottawa, Ontario, Canada, K1H 8L6 Mount Sinai Hospital - Toronto Toronto, Ontario, Canada, M5G 1X5 Princess Margaret Hospital Toronto, Ontario, Canada, M5G 2M9 Collapse <<
  NCT00005624	Multiple Myeloma	Phase 2	Completed	-	United States, Florida ... more >> H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida, United States, 33612 Collapse <<

• 参考文献

• [1] Moradei OM, Mallais TC, et al. Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. J Med Chem. 2007 Nov 15;50(23):5543-6.

  [2] Loprevite M, Tiseo M, et al. In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines. Oncol Res. 2005;15(1):39-48.

  [3] Moradei OM, Mallais TC, Frechette S, et al. Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. J Med Chem. 2007;50(23):5543-5546. doi:10.1021/jm701079h

  [4] Loprevite M, Tiseo M, Grossi F, et al. In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines. Oncol Res. 2005;15(1):39-48. doi:10.3727/096504005775082066

  [5] Zhang S, Fujita Y, Matsuzaki R, Yamashita T. Class I histone deacetylase (HDAC) inhibitor CI-994 promotes functional recovery following spinal cord injury. Cell Death Dis. 2018;9(5):460. Published 2018 May 1. doi:10.1038/s41419-018-0543-8

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