During the last decade, the research from many groups around the world, has contributed to our current understanding of Pannexin 1 as well as its involvement in many diseases.
Pannexin 1 channels are membrane channels, which are closed under normal, but open under pathophysiological conditions. Once open, they release ATP into the extracellular space with detrimental consequences. As part of the extracellular purinergic signaling, ATP activates purinoceptors, whose activation regulates cellular membrane potential and intracellular Ca2+ levels.
Discovery and validation of Panx1 opens path to develop selective Panx1 blockers to treat many severe diseases – Pannex Therapeutics leading development of effective Panx1 blocker
Overactivation of the Panx1-P2X7 signal some complex under pathological conditions, contributes to diseases like chronic pain, neurodegeneration, rheumatic immune diseases, inflammation, cancer and other diseases.
Blocking Pannexin 1 channels is a new pharmacological target and a new therapeutic approach to many severe diseases, with high unmet medical needs. Pannexin 1 channels have been vastly validated as a therapeutic target in animal models of many diseases.
To design and develop the best Pannexin 1 channel blockers we are using a modified version of rational drug design, using in silico models, channel docking studies with the 3D structure of human Panx1, ATP release tests and other screening tests.
We are developing a unique platform of first-in-class, highly effective and specific Pannexin1 blockers, to design specific candidates to target a variety of therapeutic areas/diseases.
Example of docking pose
painkillers to save lives
Chronic pain is dicult to cure and very commonly, treatment is only partially effective, and is geared toward optimizing pain management to improve function and reduce suffering. It has one of the biggest negative impact on quality of life with a high burden on sufferers and their familiess. High annual cost for health care system and society is estimated to be $635 billion (USA). In general, there are two broad categories of medications used for pain management: non- opioids and opioid classes of medications. The dilemma of treating chronic pain lays with the ecacy/risk ratio of these options and the risk of undertreating pain, if pain cannot be reduced through non-opioid approaches Current treatment for chronic pain traditionally involves a combination of non-steroidal anti-inflammatory drugs, opioids, antidepressants, anticonvulsants, muscle relaxant, surgical interventions as well as therapeutic exercise.
Chronic pain, opioid addiction
and Pannexin 1 channels.
Although discovered only during the last decade, the involvement of Pannexin 1 channels in chronic pain has been shown by several research groups, and has been validated by Dr. Bravo, the founder of Pannex Therapeutics, in animal models, showing that unspecific Pannexin1 channel blockers can significantly reduce chronic pain. In other animal models it could be demonstrated that mice without Pannexin1 expression (knock out model) and mice treated with an unspecific Pannexin1 channel blocker displayed no opioid addiction, after increase of morphine dosage. Therefore blocking Pannexin 1 channels could be a new approach to prevent opioid addiction.
Pannexin 1, a new target for many diseases
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