“Protectans” mitigate effects of therapeutic radiation on healthy cells.

A company called Cleveland BioLabs, now based in Buffalo, NY, has an interesting discussion of their investigational pipeline involving radiation-sparing medicines. I have included the link here and also copied the webpage below.

“Background

The scientific foundation of Cleveland BioLabs’s product development efforts is based upon proprietary discoveries of the molecular mechanisms underlying a form of cell death called apoptosis. Apoptosis is a highly specific and tightly regulated form of cell death that can be initiated by a variety of external and internal stresses including exposure to radiation or toxic chemicals. For example, exposure to high doses of radiation is lethal due to massive cell loss through apoptosis in radiosensitive tissue such as the hematopoietic (HP) system and the gastrointestinal (GI) tract (“Acute Radiation Syndrome” (ARS)). In addition, apoptotic death of bystander non-tumor cells accounts for the dose-limiting toxicity of anti-cancer radio- and chemotherapy that affects more than 70% of patients. Apoptosis is also a major determinant of tissue damage caused by acute medical conditions involving ischemia (lack of sufficient blood flow) such as cerebral stroke, heart attack and acute renal failure. On the other hand, apoptosis can serve as a protective mechanism that allows the body to rid itself of defective cells, such as those that have gained malignant potential and would develop into tumors if not eliminated. Thus, strategic manipulation of apoptosis has a wide range of potential therapeutic applications.

Based upon research by the founder and Chief Scientific Officer of CBLI, Dr. Andrei Gudkov, we have developed novel proprietary strategies to target the molecular mechanisms controlling apoptotic cell death for therapeutic gain. These strategies exploit naturally occurring differences in the way tumor cells and normal cells respond to genotoxic (DNA-damage-inducing) stresses such as radiation. As illustrated in the Figure below, tumor cells are typically characterized by defects in stress-induced apoptotic pathways. Such defects frequently include inactivation of the p53 tumor suppressor and/or constitutive activation of NF-kappaB signaling. Thus, while normal cells undergo apoptosis in response to radiation, tumor cells die through other non-apoptotic pathways.

CBLI is focused on development of two general classes of apoptosis-modulating pharmaceuticals:

1. Protectans are compounds that block stress-induced apoptosis. Since the targeted pathway is typically only functional in normal cells, Protectans have the potential to specifically protect normal, but not tumor, cells from death in the face of stress. CBLI’s lead Protectan compounds, CBLB502 and CBLB600 Series, are optimized derivatives of microbial factors that are natural regulators of apoptosis. Our expectations for these rationally designed compounds have been borne out in extensive preclinical studies showing that Protectans rescue mammals exposed to lethal doses of radiation by protecting the vulnerable HP and/or GI systems. Protectans may be useful in counteracting the effects of radiation exposure in military, terrorist attack and nuclear accident settings, in protecting cancer patients from the negative side effects of radiation and chemotherapy, and in limiting ischemia-induced tissue damage. CBLI’s recent discovery that CBLB600 Series Protectans also regulate proliferation and mobilization of hematopoietic stem cells opens up another wide array of potential applications for these drugs.
2. Curaxins are small molecules designed to reactivate apoptotic pathways in tumor cells by simultaneously restoring p53 function and inhibiting NF-kappaB activity. Curaxins induce apoptosis in a broad range of human tumor cells, yet have no effect on normal cells. Curaxins also sensitize tumor cells to the apoptosis-inducing effects of other cancer treatments. Thus, Curaxins may be useful either as a monotherapy or as an adjuvant to other therapies for a number of human malignancies including renal cell carcinoma, hormone-refractory prostate cancer, soft-tissue sarcoma and myeloma. CBLI’s first generation Curaxin, CBLC102, has demonstrated safety and activity in a Phase II clinical trial in patients with hormone-refractory prostate cancer. In addition, CBLI has successfully identified a lead next generation Curaxin compounds that have demonstrated reliable anti-tumor effects in animal models of colon, breast, renal and prostate cancers. These next generation compounds have favorable pharmacological characteristics, are suitable for oral administration and demonstrate a complete lack of genotoxicity. They share all of the positive aspects of CBLC102, but significantly exceed the former compound’s activity and efficacy in pre-clinical tumor models. Development of the next generation compounds will be conducted through Incuron, a joint venture between CBLI and BioProcess Capital Ventures. “

I haven’t had a chance to investigate the literature publication record for these compounds, but they sound novel and potentially very useful.

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