The Safety and Efficacy of KAI-1678— An Inhibitor of Epsilon Protein Kinase C (εPKC)—Versus Lidocaine and Placebo for the Treatment of Postherpetic Neuralgia: A Crossover Study Design

Abstract

We conclude that KAI-1678 is not efficacious as an acute analgesic for chronic neuropathic pain because of PHN. However, for the first time, the results demonstrate that subcutaneous infusions of lidocaine are effective in treating neuropathic pain. The results of lidocaine treatment also indicate that the crossover study design was adequate to detect a clinically meaningful response in this analgesia study.

Cell-penetrating peptides: strategies for anticancer treatment

“…Despite the large number of preclinical and clinical trials that have been conducted (or are currently underway), no CPP or CPP conjugate has gained US Food and Drug Administration (FDA) approval as a cancer therapeutic. The CPP conjugate cyclosporinoctaarginine (PsorBan, by CellGate Inc.) has been used for topical therapy in psoriasis [80], and CPPs have also been used to treat wrinkles [81], minimize fibrosis or scarring [82], in myocardial infarction and spinal cord injury [83,84], inflammation [83,84], and many other therapeutic applications. A few clinical trials are currently underway that use CPPs for cancer therapy.…”

Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease

“…However, the δV1-1 peptide did not show any significant effect in phase II trials in humans (Lincoff et al, 2014). A similar peptide derived from the C2 domain of PKCε, εV1–2 (aa 14–21, KAI-1678), has a 100-fold selectivity for PKCε over other enzymes and showed efficacy in animal models for prevention of heart failure (Inagaki, Koyanagi, Berry, Sun, & Mochly-Rosen, 2008) and for the inhibition of inflammatory pain (Sweitzer et al, 2004), but again did not show any significant effect in human clinical trials (Cousins, Pickthorn, Huang, Critchley, & Bell, 2013; Moodie, Bisley, Huang, Pickthorn, & Bell, 2013). …”

The Lipid Kinase PIP5K1C Regulates Pain Signaling and Sensitization

“…Indeed, drugs that block signaling proteins that are several steps downstream from receptor activation, including protein kinase Cε (PKCε) and mitogen activated protein kinases (MAPKs), reduce nociceptive neuron sensitization, thermal hyperalgesia and mechanical allodynia in animal models (Aley et al, 2001; Aley et al, 2000; Cesare et al, 1999; Cheng and Ji, 2008; Dai et al, 2002; Ji et al, 2009; Ji et al, 2002). However, drugs that inhibit PKCε or MAPKs have shown modest-to-no efficacy in treating different pain conditions in humans (Anand et al, 2011; Cousins et al, 2013; Ostenfeld et al, 2013; Tong et al, 2011). This limited efficacy does not mean that PKCε or MAPK inhibitors cannot be used to treat pain, as drugs can show limited-to-no efficacy for a number of reasons, including the drugs may not engage their molecular target in humans or the drugs may lack efficacy in some pain conditions but not others.…”