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KDM5 Selective Inhibitors for the Treatment of Multiple Myeloma and Other KDM-dependent Diseases

Novel compounds inhibit KDM5’s enzymatic activity with greater potency compared with current KDM5 inhibitors.

  • Therapeutics

Project Overview

  • Recent studies provided new pathophysiological insights in the role of epigenetic proteins including histone lysine demethylases (KDMs) in multiple myeloma (MM). Specifically, inhibition of KDMs has demonstrated antitumor effects. 
  • One of these KDMs is lysine demethylase 5A (KDM5), which is involved in the development, differentiation, tumorigenesis, metastasis, and drug resistance in various cancers making makes it a promising therapeutic target.
  • Dana-Farber scientists have created a number of KDM5 inhibitors that are available for licensing.

Technology

Dana-Farber scientists have developed a series of novel compounds that inhibit KDM5’s enzymatic activity with greater potency compared to reported KDM5 inhibitors. Importantly, the new KDM5 inhibitors have a proven selectivity for the KDM5 family over other KDM subfamilies. Both in vitro and in vivo findings reveal the promise of these inhibitors as novel therapeutic strategies in MM and other KDM5A-dependent malignancies. 

The series of new KDM5 inhibitors offers the following advantages: 

  • Superior potency over reported KDM5A inhibitors as demonstrated by double-digit nM IC50 cell assay values. 
  • High selectivity for the KDM5 subfamily of KDMs, illustrated by a KDM5B_alphascreen activity assay. 
  • Significantly prolonged survival rates in mice treated with KDM5 inhibitors compared to a control group. 

Team Members: Jun Qi, PhD, Paul M. Park, PhD, Chengkui Pei, PhD

Applications

The technology offers a new research tool to study the role of KDM5 while the proven selectivity and early efficacy in vivo data show great promise for these KDM5 inhibitors as a new therapeutic strategy for MM and related cancers, and cardiovascular disease.

Interested in learning more?

Interview with Jun Qi explaining KDM5 function and inhibition in multiple myeloma – 2021

Jun Qi KDM5 AACR 2021 interview

Opportunities

Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development into new oncology therapeutics. 

Get in touch

Team Members

Jun Qi, PhD

Department of Cancer Biology and Medical Oncology, Dana-Farber

Assistant Professor, Harvard Medical School