Arno Therapeutics today announced it has entered into a Cooperative Research and Development Agreement (CRADA) Material Transfer Agreement with the US Army Medical Research Institute of Infectious Diseases (USAMRIID) to evaluate the anti-viral activity of AR-12 and various analogues against Ebola and other viruses of biodefense interest.
AR-12 is an orally-available small molecule. Data reported previously demonstrate that the AR-12 mechanism of action may include induction of host cell autophagy and inhibition of fungal acetyl coenzyme A synthetase.
The precise antiviral mechanism of action of AR-12 continues to be evaluated but an established body of evidence demonstrates that AR-12 is an inducer of host effector cell autophagy. AR-12 is known to inhibit, or down regulate, GRP78 (also known as BiP, HSPA5) the master regulator of the unfolded protein response.
The down regulation of GRP78 results in the up-regulation of PERK which induces the formation of autophagosomes and, subsequently, host cell autophagy. AR-12 also down regulates the chaperone proteins HSP70 and HSP90. Previously, AR-12 has completed Phase 1 clinical trials in patients with cancer. Additional pre-clinical research indicates that AR-12 may have potential as an antimicrobial agent in various infectious diseases.
AR-12 has been granted two orphan drug designations in Europe for the treatment of cryptococcosis and tularaemia.
“This is an important step forward in the process of evaluating AR-12 and the other compounds in the AR-12 series against various microbial pathogens,” commented Alex Zukiwski, MD, Chief Executive Officer of Arno Therapeutics. “We look forward to working with USAMRIID to learn more about the potential activity of AR-12 and related compounds.”
Arno also has the rights to a broad portfolio of compounds in the “AR-12 series” which have been demonstrated to have broad spectrum antimicrobial activity.
