KAI-1678: A novel PKC-epsilon inhibitor



KAI-1678, a synthetic 21-amino acid, is a novel PKC-epsilon (ε-PKC) inhibitor with a molecular weight of 2541 Daltons. Meanwhile, it is a cell-permeable peptide composed of an active inhibitor of ε-PKC conjugated to a carrier peptide to aid delivery to the targeted intracellular site of action. The active moiety, an inhibitor of ε-PKC, is an 8-amino acid peptide, termed ε-V1-2 (EAVSLKPT). The carrier moiety is an arginine-rich 11-amino acid peptide derived from the transactivator (TAT) protein. It was developed to competitively and selectively inhibit the interaction of ε-PKC and its ε-RACK. Meanwhile, it can reduce hyperalgesia in a variety of inflammatory and neuropathic pain models. These studies suggest that KAI-1678 may represent a new therapeutic approach for the treatment of pain.

Pharmacologic action

KAI-1678 is a novel peptide that competes with activated ε-PKC for binding to its isozyme-specific docking protein, thus preventing ε-PKC translocation. Furthermore, KAI-1678 contains the peptide sequence -EAVSLKPT- that has been shown to block ε-PKC translocation and reduce hyperalgesia in a variety of inflammatory and neuropathic pain models. Preclinical pharmacology studies evaluated the efficacy of KAI-1678 in a carrageenan acute inflammatory pain model, as well as chronic constriction injury and L5 spinal nerve transaction rodent models of peripheral neuropathy. At the same time, the safety profile of KAI-1678 reveals that the compound is safe and well tolerated.


KAI-1678 has been shown to be highly effective in reversing pain for both neuropathic and inflammatory pain, both of which have well validated epsilon PKC. Phase II clinical trial validated a selective, intracellular peptide-based ε-PKC inhibitor is effective in reversing allodynia, which is a primary component of neuropathic pain. Laboratory abnormalities of two patients were reported at prespecified clinically significant levels during the KAI-1678 infusion periods; levels of hemoglobin, hematocrit, and calcium is decreased in one patient, and calcium levels is decreased in another patient. Overall, administration of KAI-1678 and lidocaine is generally safe and well tolerated, with the most common adverse effects being headache and pain at the infusion site.

Pharmacokinetics and metabolism

The ε-PKC amino acid sequence that is mimicked in KAI-1678 is identical in rat and human, suggesting that similar pharmacology should occur in both species. Some studies have been conducted to demonstrate that KAI-1678 is taken up by various tissues after an intravenous injection. Fortunately, it can be quickly cleared from the systemic circulation.


1. Michael J. Cousins, MBBS, Karen Pickthorn, The safety and efficacy of KAI-1678-An inhibitor of epsilon protein kinase C (ε-PKC)-versus lidocaine and placebo for the treatment of postherpetic neuralgia: A crossover study design. Pain Medicine, 2013, 14, 533-540.

2. John E. Moodie, MB ChB, FRCA, FANZCA, A single-center, randomized, double-blind, active, and placebo-controlled study of KAI-1678, a novel PKC-epsilon inhibitor, in the treatment of acute postoperative orthopedic pain. Pain Medicine, 2013, 14, 916-924.

3. Velazquez KT, Mohammad H, Sweitzer SM. Protein kinase C in pain: Involvement of multiple isoforms. Pharmacol Res, 2007, 55, 578-589.

Creative Peptides has accumulated a huge library of peptide knowledge including frontier peptide articles, application of peptides, useful tools, and more!

  Resveratrol is also known as stilbene III. Its chemical name is (E)-3,5,4-trihydroxystilbene. It is a non-fla ...

An overview of Tripeptide-10 Citrulline  Signal oligopeptides are commonly synthesized from portions of EMPs and from natural ...

 Corticotropin-releasing factor (CRF) is a 41 amino acid peptide that is an important hormone in the hypothalamic ...

 The peptide st-Ht31 P, A-kinase anchoring protein (AKAP) inhibitor, has the negative control for st-Ht31. In DRG ...

 DAPTA (D-[Ala]-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-amide), D-Ala-Peptide T amide, is one of analogue of peptide T, which ...

Contact Us



Tel: |




Copyright © 2024 Creative Peptides. All rights reserved.