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Kindolor: the network approach to treating chronic pain

Network models suggest that partial inhibition of a surprisingly small number of targets can be more efficient than the complete inhibition of a single target.

Csermely et al., 2005

Lohocla Research Corporation rationally designed a novel small molecule that we named Kindolor for treatment of chronic pain syndromes. The molecule reduces the over-activity of the nociceptive (pain-sensing) peripheral neural network that generates chronic pain. Kindolor has negligible penetrance into the brain, thus reducing deleterious CNS side effects. Accordingly, Kindolor’s actions are confined to the peripheral nervous system, where Kindolor has been shown to produce significant anti-hyperalgesic effects in five animal models of chronic pain. No genotoxic effects of Kindolor have been noted. Acute dosing levels 20 to 30 times higher than doses producing therapeutic effects produced no overt signs of toxicity, and we estimate the therapeutic index for Kindolor to be greater than 30.
Fig. A
Kindolor and network pharmacology.
Illustrates the peripheral nociceptive transmission pathway. Kindolor selectively modulates the activity of key nodes in this nociceptive pathway, attenuating over-activity.


Over 100 million adults in the U.S. suffer from intermittent or constant chronic pain, and chronic pain affects at least 10 percent of the world’s population. The primary pharmaceuticals for treatment of chronic pain have been natural or synthetic opioids. However, the use of opioids for pain treatment has resulted in an “epidemic” of opioid abuse, addiction, and lethal overdoses. Through a process of rational drug design, Lohocla Research has generated a new chemical entity (NCE) called Kindolor. Kindolor is a non-opiate, non-addicting molecule that was developed specifically to target the aberrant over-activity of the peripheral sensory system that is integral in the initiation and propagation of chronic pain. Kindolor dampens the over-activity of the signaling network that conducts and magnifies pain signals (Fig. A), but leaves the normal response to acute painful stimuli intact. Lohocla Research has developed a process to synthesize Kindolor at 99 percent purity. Pre-clinical studies have demonstrated the efficacy of Kindolor to reduce or eliminate chronic pain generated in five animal models at doses compatible with use of Kindolor in humans. Initial evidence demonstrates the safety (high TI) of Kindolor as well as its uneventful metabolism. Additional attractive features of Kindolor are that it can prevent the development of chronic pain if given soon after tissue injury. Additionally, if combined with low doses of opiates, Kindolor produces a substantial “opiate sparing” effect through synergistic actions with the opiates. Lohocla Research is working to bring Kindolor to the public. An IND application is in process, and Phase 1 trials are planned for early 2023, followed by Phase 2 trials for efficacy in treating diabetic neuropathy. In all, our goal is to license to or partner with a Pharma company willing and able to bring this innovative medication to the chronic pain sufferer.

Public Health Relevance Statement

The U.S. and other countries around the world are facing “dual crises of pain and opioid addiction.” Lohocla Research Corporation has responded to the opioid crisis and medication development challenge by designing, synthesizing, and demonstrating, in pre-clinical studies, the efficacy and safety of a non-opiate, non-addictive new chemical entity (NCE) for treatment of chronic pain. This NCE, called Kindolor, has significant additional benefits of being able to prevent the development of chronic pain if administered soon after tissue injury, including post-operative conditions. Kindolor also has a highly significant “opiate sparing” effect in conditions that may require the use of opiates, since Kindolor demonstrates a strong synergistic effect with morphine. Given the FDA approval of our IND status, we will complete first-in-human, Phase I clinical studies for safety and Phase 2a studies of efficacy to bring our medication to chronic pain sufferers.