Curaxins are synthetic small molecules designed to simultaneously target major cell stress response pathways that are frequently deregulated in cancer. Although their ability to activate p53 and inhibit NF-kappaB has been known as a signature property of these molecules, the mechanism through which Curaxins caused these effects remained unknown. The peer-reviewed paper describes the manner in which Curaxins act by intercalating in the minor groove of DNA, resulting in FACT trapping chromatin, thus making the cell deficient in this factor. Trapped FACT stimulates activation of the major tumor suppressor protein p53 that is commonly inactive in tumors. At the same time, trapping FACT makes the tumor cell incapable of conducting its normal functions, such as promoting NF-kappaB, an important pro-survival factor that is constitutively active in tumors and plays the role of an oncogene. Importantly, the mechanism of action of Curaxins does not involve DNA damage, a typical side effect of conventional chemotherapy drugs.
Andrei Gudkov, Ph.D., D.Sci., Chief Scientific Officer of Cleveland BioLabs and Incuron, LLC, and Senior Vice President of Basic Science at Roswell Park Cancer Institute, commented, "The findings highlighted by this publication introduce both a novel anticancer target and a new class of DNA intercalators that exert their function without genotoxic effects. By hitting multiple cancer treatment targets, Curaxins resemble long known and very efficacious anticancer drugs, such as doxorubicin or cisplatin, but without their genotoxicity, which is the main challenge of historical chemotherapies. Our studies continue to reinforce our belief that Curaxins are promising drug candidates that may be effective against a wide range of cancer types. Our hope is that the lack of mutagenic activity and multi-targeted nature of Curaxins should make it difficult for tumors to develop treatment resistant variants, the most common obstacle of cancer therapy."
Curaxins are being developed by Incuron, LLC, a Moscow-based joint venture between Cleveland BioLabs and Bioprocess Capital Ventures. A multi-center, Phase I single-dose ascending trial of CBLC102 (the predecessor of these Curaxins, formerly known as anti-malaria drug quinacrine), is ongoing in patients with gastrointestinal and liver tumors in The Russian Federation.
A Phase I clinical trial of the oral formulation of next generation Curaxin CBLC137 in solid tumors is planned to start in the first quarter of 2012 in The Russian Federation. An intravenous formulation of the compound is currently being developed to further optimize the bioavailability of CBLC137, with plans to initiate a Phase I trial in the United States as soon as formal preclinical toxicology and other preparations supporting an Investigational New Drug Application (IND) filing are completed.
The Science Translational Medicine publication may be found online at: http://www.sciencetranslationalmedicine.org/
About Cleveland BioLabs, Inc.
Cleveland BioLabs, Inc. is a drug discovery and development company leveraging its proprietary discoveries around programmed cell death to develop treatments for cancer and protection of normal tissues from exposure to radiation and other stresses. The Company has strategic partnerships with the Cleveland Clinic, Roswell Park Cancer Institute, ChemBridge Corporation and the Armed Forces Radiobiology Research Institute. To learn more about Cleveland BioLabs, Inc., please visit the company's website at www.cbiolabs.com.
About Incuron, LLC
Incuron, LLC is a joint venture between Russian Closed Mutual Venture Fund "Bioprocess Capital Ventures," and Cleveland BioLabs, Inc. Bioprocess Capital Ventures is a Russian Federation Venture Capital Fund managed by "Bioprocess Capital Partners, LLC," which was founded by several Russian investors including "Russian Venture Company," JSC and state corporation VneshEconomBank (VEB). The Fund focuses on investments in innovative projects in the pharmaceutical, biotechnology, and fine chemistry sectors of the economy. Incuron's strategy includes preclinical and clinical development of breakthrough biotechnologies discovered by CBLI with the subsequent introduction of brand new anticancer drugs with novel mechanism of action ("Curaxins") to both Russian and American markets.