Detail of "209783-80-2"

Reference

Treatment of patients with chronic lymphocytic leukemia

Treatment of patients with chronic lymphocytic leukemia. Lucas, David M.; Parthun, Mark R.; Byrd, John C.; Grever, Michael R. ( The Ohio State University, USA). U.S. US 6841565 B1 11 Jan 2005, 13 pp. (English). (United States of America). CODEN: USXXAM. CLASS: ICM: A61K031-44. NCL: 514346000; 514352000; 514357000. APPLICATION: US 2003-403667 31 Mar 2003. PRIORITY: US 2002-PV368775 29 Mar 2002. DOCUMENT TYPE: Patent CA Section: 1 (Pharmacology) Section cross-reference(s): 15 The invention provides methods for treating a patient with chronic lymphocytic leukemia of B cells (B-CLL). One method comprises administering to a patient with B-CLL, one or more benzamide derivs. (Markush structure is given), the benzamide derivs. including MS-275 and related compds. Another method comprises administering to a patient with B-CLL, one or more of the benzamide derivs., and addnl. administering to the patient one or more antibodies immunospecific for 1D10 antigen. Addnl.In this experiment, several chemicals are used like 209783-80-2 and 209783-77-7 methods for inducing apoptosis of B-CLL cells and for increasing expression of 1D10 antigen in B-CLL cells using the benzamide derivs. are also provided. .

Identification of novel isoform-selective inhibitors within class I histone deacetylases

Identification of novel isoform-selective inhibitors within class I histone deacetylases. Hu, Erding; Dul, Edward; Sung, Chiu-Mei; Chen, Zunxuan; Kirkpatrick, Robert; Zhang, Gui-Feng; Johanson, Kyung; Liu, Ronggang; Lago, Amparo; Hofmann, Glenn; MacArron, Ricardo; de los Frailes, Maite; Perez, Paloma; Krawiec, John; Winkler, James; Jaye, Michael ( Department of Vascular Biology, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA). Journal of Pharmacology and Experimental Therapeutics, 307(2), 720-728 (English) 2003 American Society for Pharmacology and Experimental Therapeutics. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Histone deacetylases (HDACs) represent an expanding family of protein modifying-enzymes that play important roles in cell proliferation, chromosome remodeling, and gene transcription. We have previously shown that recombinant human HDAC8 can be expressed in bacteria and retain its catalytic activity. To further explore the catalytic activity of HDACs, we expressed two addnl. human class I HDACs, HDAC1 and HDAC3, in baculovirus. Recombinant HDAC1 and HDAC3 fusion proteins remained sol. and catalytically active and were purified to near homogeneity. Interestingly, trichostatin (TSA) was found to be a potent inhibitor for all three HDACs (IC50 value of ~0.1 - 0.3 mM), whereas another HDAC inhibitor MS-27-275 (N-(2-aminophenyl)-4-[N-(pyridin-3-methyloxycarbonyl)-aminomethyl]be nzamide) preferentially inhibited HDAC1 (IC50 value of ~0.3 mM) vs. HDAC3 (IC50 value of ~8 mM) and had no inhibitory activity toward HDAC8 (IC50 value >100 mM). MS-27-275 as well as TSA increased histone H4 acetylation, induced apoptosis in the human colon cancer cell line SW620, and activated the simian virus 40 early promoter. HDAC1 protein was more abundantly expressed in SW620 cells compared with that of HDAC3 and HDAC8. 209783-80-2 and 119978-65-3 which are cas registry numbers of substances are two of reagents here. Using purified recombinant HDAC proteins, we identified several novel HDAC inhibitors that preferentially inhibit HDAC1 or HDAC8. These inhibitors displayed distinct properties in inducing histone acetylation and reporter gene expression. These results suggest selective HDAC inhibitors could be identified using recombinantly expressed HDACs and that HDAC1 may be a promising therapeutic target for designing HDAC inhibitors for proliferative diseases such as cancer. .