Pipeline

Scientific Background on ATP and NO

Adenosine triphosphate (ATP)

ATP is a natural substance found in every cell of the human body. The energy of chemical bonds within each molecule of ATP is used to fuel all functions of the human body. ATP is released from cells into the extracellular space under physiologic as well as disease conditions. Extracellular ATP activates the P2 receptors (P2R) and thereby exerts specific actions depending on the subtype of receptor activated and the targeted cell type. Thus, ATP is a physiologic regulator acting as a natural agonist that activates P2R. Fifteen P2 receptors have been cloned heretofore. They are divided into two main categories: P2Y – G protein coupled receptors that control intracellular signal transduction pathways, and P2X ionic channels embedded in the cell membrane that once activated, allow the flux of certain ions across the cell membrane.

MOLECULAR STRUCTURE OF ATP
The chemical formula of the sodium salt form of ATP is: C₁₀H₁₄N₅Na₂O₁₃P₃

Cordex’s investigational products, ATPace, Vagonixen and ATPotent, target specific P2Y and P2X receptor subtypes. The activation or blockade of these receptors can be used for diagnostic and therapeutic purposes. Cordex’s proprietary technology enables it to expand its product portfolio.

ATP formulations have been marketed as approved pharmaceuticals in Europe for a number of medical indications for over 50 years. Significant clinical data that have been generated with ATP by clinical scientists in Europe is used by Cordex in support of its 505(b)(2) New Drug Application for ATPace.

Nitric Oxide (NO)

Nitric oxide (NO), an endogenously produced gas molecule, is believed to play a key role in cellular signal transduction. In 1995, Science Magazine named NO “Molecule of the Year.” In 1998, the Nobel Prize was awarded for the discovery of the physiological regulatory functions of NO. Furthermore, the manipulations of NO signal transduction pathways have been proven as a validated pharmaceutical commercial opportunity. It is the mechanism of action behind the blockbusters VIAGRA®, Cialis® and LEVITRA®.

Cordex's scientific consultants have conducted research on nitric oxide-redox imbalance in the failing heart and cardiovascular system. This research has yielded key evidence that altered production and distribution of reactive oxygen and nitric oxide species damages the cardiovascular system and contributes to the poor pumping capacity that characterizes the failing heart.

Until recently, researchers were unaware that a major way in which nitric oxide influences heart function is by activating the main calcium channel in the heart to release calcium from intracellular stores. Calcium is the primary determinant of contractility in the heart. A deficiency in nitric oxide disrupts the calcium cycle, inhibits heart contractility, and ultimately causes the heart to fail.

Hare J. — New England Journal of Medicine, 2004

Hare JM. Nitroso-Redox Balance in the Cardiovascular System. The New England Journal of Medicine. 2004;351:2112-2114. Link to Article

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