Delving into the Latest Updates on KAI-1678 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Target

PKCε

Mechanism

PKCε inhibitors(protein kinase C epsilon inhibitors)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Neuralgia, PostherpeticPain, PostoperativeSpinal Cord Injuries

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

KAI Pharmaceuticals, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC107H190N44O28

InChIKeyUVKJMACBAZMKAL-IAPYPFBNSA-N

CAS Registry1041004-14-1

Gene Sequence

Sequence Code 1661307

Source: *****

OBJECTIVEKAI-1678, a novel inhibitor of the interaction of the epsilon isoform of protein kinase C (εPKC) with its intracellular receptor, has demonstrated activity in countering hyperalgesia in several models of pain. In this controlled randomized trial, KAI-1678 was tested for analgesic activity in an orthopedic acute postoperative pain setting.DESIGNFollowing hip or knee replacement surgery, subjects were treated with KAI-1678, ketorolac, or saline. Subjects recorded their pain intensity on a visual analog scale and rated their quality of analgesia. The pain intensity differences between baseline and the evaluations were summed over the first 4 hours.RESULTSThe analysis revealed that, while ketorolac displayed good analgesic activity, KAI-1678 was not significantly different than placebo. Analgesia quality ratings similarly did not show a difference between KAI-1678 and placebo in this pain model. A small excess of infusion site erythema was seen with KAI-1678, but otherwise the drug was safe and well tolerated.CONCLUSIONSWe investigated the safety and efficacy of a novel inhibitor of εPKC and provide clinical evidence that inhibition of εPKC with KAI-1678 is not effective in the treatment of acute postoperative orthopedic pain.

01 Apr 2013·Pain MedicineQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: Michael J. Cousins ; Karen Pickthorn ; Linda Critchley ; Saling Huang ; Gregory Bell

OBJECTIVEPostherpetic neuralgia (PHN) occurs in approximately 10-20% of patients with herpes zoster, and the risk increases with age. In this clinical trial, we evaluated the analgesic properties of KAI-1678-an inhibitor of epsilon protein kinase C-in the treatment of neuropathic pain in patients with PHN.DESIGNThe study was a three-treatment period, double-blind, randomized, placebo and active comparator crossover trial evaluating subcutaneous infusions of KAI-1678 (25 mg), placebo, and lidocaine hydrochloride (700 mg; active comparator).PATIENTSA total of 17 men and 6 women (N = 23) were enrolled after fulfilling diagnosis of PHN with pain persisting for ≥3 months after a segmental herpes zoster eruption. Patients had to have a mean average pain score of ≥4 points on an 11-point numerical rating scale (NRS; ranging from 0 to 10) based on at least three daily entries prior to participation in the subsequent treatment period.RESULTSOverall, administration of KAI-1678 was generally safe and well tolerated. However, compared with placebo, KAI-1678 did not improve clinical pain scores as recorded using the NRS (0-10). In contrast, subcutaneous infusions of lidocaine were associated with a significant reduction in pain intensity at the end of the infusion.CONCLUSIONSWe 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.

01 Jun 2009·Recent Patents on DNA & Gene Sequences

PKC Delta and Epsilon in Drug Targeting and Therapeutics

Review

Author: Inoko, Hidetoshi ; Kurata, Riho ; Kimura, Minoru ; Yonezawa, Tomo

Protein kinase C (PKC) belongs to the serine and threonine kinase family. At least ten PKC isoforms have been identified and subdivided into three groups: classical (alpha, beta I, beta II and gamma), novel (delta, epsilon, theta and eta), and atypical (zeta and iota/lambda). Two calcium-insensitive isoforms of novel PKC, PKC delta and epsilon, have received particular attention as promising targets for new drugs. PKCs play a multifaceted role in cellular responses in a range of tissues. Professor Mochly-Rosen's group and KAI Pharmaceuticals Inc. have developed drugs targeted against PKC delta (KAI-9803) and epsilon (KAI-1678). These drugs ameliorate pathological conditions in acute myocardial infarction and reduce pain via specific modulation of membrane-translocation of PKC delta or epsilon. Another research group has recently used the KinAce() approach to produce PKC epsilon-abrogating peptides (KCe-12 and KCe-16) that are based on the catalytic domain of PKC. These peptides specifically inhibit PKC epsilon and ameliorate pathological conditions in a rodent insulin resistance model. This review describes the development of these therapeutic drugs targeting PKC delta and epsilon by two independent groups in the light of recent patents.

100 Deals associated with KAI-1678

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16211

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neuralgia, Postherpetic	Phase 2	AU	KAI Pharmaceuticals, Inc.	01 Mar 2009
Spinal Cord Injuries	Phase 2	AU	KAI Pharmaceuticals, Inc.	01 Mar 2009
Pain, Postoperative	Discovery	NZ	KAI Pharmaceuticals, Inc.	01 Dec 2008