OXiGENE, Inc., a clinical-stage, biopharmaceutical company developing novel therapeutics to treat cancer and eye diseases, announced the presentation of positive preclinical data supporting development of its novel, non-peptidic cathepsin L inhibitors as anticancer agents. The data were presented at the 102nd Annual Meeting of the American Association of Cancer Research in Orlando, Florida.
Cysteine cathepsins are a family of lysosomal proteases that are often up-regulated in a variety of cancers and that have been implicated in key processes in cancer progression. Small molecule inhibitors of the cysteine protease cathepsin L have the potential to limit degradation of extracellular matrix in the normal tissue surrounding the tumor, thus retarding cancer metastasis. It has also been established that cathepsin L is involved in blood vessel development, and thus inhibitors have the potential to suppress tumor growth and dissemination through an anti-angiogenic effect.
“The discovery of new chemotherapeutic strategies for inhibiting the growth and spread of cancer, such as our novel class of cathepsin inhibitors, represents an important achievement in the effort to enhance both cancer patient quality of life and survival. We are very encouraged by the preclinical safety and efficacy data presented at the AACR meeting with our small molecule cathepsin L inhibitors. Our goal is to advance these promising agents towards clinical evaluation,” said Dr. Dai Chaplin, OXiGENE’s Chief Scientific Officer
In a presentation titled, Abrogation of Prostate Cancer Cell Metastatic Phenotype by Cathepsin L Inhibition, Dhivya Sudhan and Professor Dietmar Siemann from The Shands Cancer Center at The University of Florida demonstrated that OXiGENE’s lead cathepsin L inhibitor, KGP94, inhibited the metastatic phenotype in the three human prostate cancer cell lines. KGP94 mediated abrogation of tumor cell migration and invasion occurred in the absence of cytotoxic effects and was a consequence of an inhibitory effect on secreted and not nuclear cathespsin-L.
Professor Siemann commented: “Our findings strongly support a mechanism of action where KGP94 affects the ability of cathepsin-L to break down extracellular matrix, which is important in invasive and angiogenic processes.”
A second presentation, titled Development and Initial Evaluation of the Antitumor Activity of a Functionalized Benzophenone Thiosemicarbazone Inhibitor of Cathepsin L, by Professors Mary Lynn Trawick and Kevin G. Pinney from Baylor University and Professor Michael Horsman from Arhus University Hospital in Denmark, demonstrated that KGP94 and other structurally related compounds inhibited the invasion and migration of DU145 prostate cancer cells through matrigel. In addition, the professors presented initial in vivo data from a mouse breast cancer model showing significant antitumor effects against both recently implanted and established tumors. These antitumor effects are consistent with a mechanism impacting tumor growth and vascularization.
Date: April 4, 2011
Source: OXiGENE, Inc.