First-in-class IKK-alpha Selective Inhibitors for Cancer Treatment

The first reported potent and selective IKK alpha inhibitors, with the lead compound achieving 60% tumour growth inhibition

Technology Overview

Scientists at Strathclyde have developed the first reported potent and selective IKK alpha inhibitors, and the lead compound has been shown to achieve 60% tumour growth inhibition in the metastatic PC3m xenograph prostate cancer model, despite its current sub-optimal PK (optimisation is ongoing). Consistent with this, in vitro studies have demonstrated a reduction in androgen receptor levels. Intriguingly, our scientists have identified a major cohort of prostate cancer patients with a specific molecular marker who have a significantly worse prognosis and in which an IKKα inhibitor could therefore potentially be of particular therapeutic benefit. This may enable an informative early-stage trial design (further data available under CDA).

Background

The pharmaceutical industry has devoted considerable effort toward generating NF-κβ pathway inhibitors, and a leading approach has been to target the IκB kinases (IKK), focused on either pan-IKK or IKKβ-selective inhibitors. However, inhibition of IKKβ has been associated with a number of side effects, including the development of inflammatory skin disease and sensitisation of colonic epithelium to a range of insults. In addition, IKKβ knockout mice display severe liver toxicity, and reports suggest intestinal and liver toxicity has been an issue in clinical trials of IKKβ inhibitors. Given the growing evidence that IKKα has an important role in a number of cancers, the development of selective IKKα inhibitors is an attractive approach, and selectivity over IKKβ may help facilitate the use of such compounds clinically.

Stage of Development

Strathclyde researchers have developed first-in-class IKKα selective compounds with in vivo data showing strong inhibition of tumour growth.

Benefits

  • first-in-class compounds
  • target unmet need
  • 60% tumour inhibition in PC3M mice

Applications

There were 1.3 million new cases of prostate cancer in 2018. Pancreatic cancer is the fifth most common cause of cancer death and has the worst survival rate of all cancers. New and effective treatments are urgently needed.