51193-27-2Relevant articles and documents
2-Aminomethylene-5-sulfonylthiazole Inhibitors of Lysyl Oxidase (LOX) and LOXL2 Show Significant Efficacy in Delaying Tumor Growth
Smithen, Deborah A.,Leung, Leo M. H.,Challinor, Mairi,Lawrence, Rae,Tang, Haoran,Niculescu-Duvaz, Dan,Pearce, Simon P.,McLeary, Robert,Lopes, Filipa,Aljarah, Mohammed,Brown, Michael,Johnson, Louise,Thomson, Graeme,Marais, Richard,Springer, Caroline
supporting information, p. 2308 - 2324 (2019/10/02)
The lysyl oxidase (LOX) family of extracellular proteins plays a vital role in catalyzing the formation of cross-links in fibrillar elastin and collagens leading to extracellular matrix (ECM) stabilization. These enzymes have also been implicated in tumor progression and metastatic disease and have thus become an attractive therapeutic target for many types of invasive cancers. Following our recently published work on the discovery of aminomethylenethiophenes (AMTs) as potent, orally bioavailable LOX/LOXL2 inhibitors, we report herein the discovery of a series of dual LOX/LOXL2 inhibitors, as well as a subseries of LOXL2-selective inhibitors, bearing an aminomethylenethiazole (AMTz) scaffold. Incorporation of a thiazole core leads to improved potency toward LOXL2 inhibition via an irreversible binding mode of inhibition. SAR studies have enabled the discovery of a predictive 3DQSAR model. Lead AMTz inhibitors exhibit improved pharmacokinetic properties and excellent antitumor efficacy, with significantly reduced tumor growth in a spontaneous breast cancer genetically engineered mouse model.
COMPOUNDS FOR TREATMENT OF CANCER
-
, (2011/10/03)
The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.
Circumventing anti-androgen resistance by molecular design
McGinley, Paula L.,Koh, John T.
, p. 3822 - 3823 (2007/10/03)
Nuclear/steroid hormone receptors (NHRs) function as ligand-dependent transcriptional regulators of diverse sets of genes involved in development and homeostasis. Mutations to the androgen receptor (AR), a member of NHRs, have been linked to the failure o
