79722-22-8Relevant articles and documents
Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer
Shouksmith, Andrew E.,Shah, Fenil,Grimard, Michelle L.,Gawel, Justyna M.,Raouf, Yasir S.,Geletu, Mulu,Berger-Becvar, Angelika,De Araujo, Elvin D.,Luchman, H. Artee,Heaton, William L.,Bakhshinyan, David,Adile, Ashley A.,Venugopal, Chitra,O'Hare, Thomas,Deininger, Michael W.,Singh, Sheila K.,Konieczny, Stephen F.,Weiss, Samuel,Fishel, Melissa L.,Gunning, Patrick T.
supporting information, p. 2651 - 2665 (2019/03/17)
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing.
Acyloxybenzyl and Alkoxyalkyl Prodrugs of a Fosmidomycin Surrogate as Antimalarial and Antitubercular Agents
Courtens, Charlotte,Risseeuw, Martijn,Caljon, Guy,Cos, Paul,Van Calenbergh, Serge
supporting information, p. 986 - 989 (2018/09/25)
Two classes of prodrugs of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. To this end, a novel efficient synthesis route was developed involving a cross metathe
Structural Requirements of Histone Deacetylase Inhibitors: SAHA Analogs Modified on the Hydroxamic Acid
Bieliauskas, Anton V.,Weerasinghe, Sujith V.W.,Negmeldin, Ahmed T.,Pflum, Mary Kay H.
, p. 373 - 382 (2016/05/19)
Histone deacetylase (HDAC) proteins have emerged as targets for anti-cancer therapeutics, with several inhibitors used in the clinic, including suberoylanilide hydroxamic acid (SAHA, vorinostat). Because SAHA and many other inhibitors target all or most o
