MENU

Novel Druggable Targets on the Interface of Oncogenic and Metabolic Pathways

FCCC Ref. 494-AP
 

Background

A fundamental feature of tumor progression is reprogramming metabolic pathways and gene regulation. ATP citrate lyase (ACLY) is a key enzyme that is a gatekeeper for the synthesis of Acetyl-CoA, a critical precursor delivering acetyl groups for fatty acid/lipid synthesis and histone acetylation/gene regulation. ACLY and the resulting lipid production and histone acetylation are found upregulated in cancer, but the molecular mechanisms underlying the ACLY upregulation have not been deciphered up to date. The recently-solved crystal structure of the homo-tetrameric enzyme ACLY (published in Nature journal on April 3, 2019) opened new avenues for targeted drug discovery of novel ACLY inhibitors. As of today, only one ACLY inhibitor, Bempedoic Acid (ETC-1002), was approved by FDA as a cholesterol lowering drug in 2019.

Summary of the Invention

Scientists at Fox Chase Cancer Center identified two oncogenic molecules that can bind directly to and activate ACLY in Acute Myeloid Leukemia cells. The discovery lays on the basis of a novel target linking the oncogenic pathways to ACLY/Acetyl-CoA metabolic pathways in leukemia and possibly in solid tumors as pancreatic cancer, breast cancer, and glioma. Testing existing inhibitors and developing novel class of inhibitors as drug candidates towards cancer (and perhaps cholesterol lowering in atherosclerotic cardiovascular disease andnonalcoholic fatty liver disease), are envisioned in collaboration with industry partner.

Advantages

  • New druggable target in cancer (leukemia and solid tumors) and likely for cholesterol lowering in atherosclerotic cardiovascular disease and nonalcoholic fatty liver disease.
  • Foundation for design and screening of new class of drugs and/or existing drugs targeting of oncogene binding to ACLY interaction interface.IP Status Patent application has been filed.

For Licensing/Partnering information, please contact:
Inna Khartchenko, MSc, MBADirector,
Technology Transfer and New Ventures
Fox Chase Cancer Center
Inna.Khartchenko@fccc.edu

Connect with Fox Chase