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Last Updated: 09/11/2019

NCI Experimental Therapeutics (NExT) Program Supports Collaborative Project to Develop Inhibitors of p97 ATPase, a Novel Cancer Therapeutic Target

The NCI’s Experimental Therapeutic (NExT) Program provides resources to domestic and international researchers in academia, non-profit, government, and industry for projects focused on developing therapies for unmet needs that are not adequately addressed by the private sector.

The NExT Pipeline

NExT Program Mission

Advance clinical practice and bring improved therapies to patients with cancer by supporting the most promising new drug discovery and development projects

Background on p97 as a Therapeutic Target

p97 is a key driver of cellular protein homeostasis, which ensures that misfolded proteins are cleared from the cytoplasm. The clearance of potentially toxic cytoplasmic proteins can create a favorable environment for cancer cells and prolong their survival. By disrupting cellular protein homeostasis, a targeted therapy that inhibits p97 can lead to an accumulation of toxic cytoplasmic proteins and ultimately, cancer cell death. NExT is supporting the development of inhibitors of p97 ATPase, which is a novel therapeutic target.

Details about the p97 Inhibitor NExT Project

  • Two p97 inhibitors are being developed with NExT Program support.
  • Mechanism of action: the inhibitors prevent ATP from binding p97, which is necessary for its activity.
  • Studies are evaluating the efficacy and toxicity of the inhibitors in vitro and in vivo.
  • Drug development is a collaborative effort among:

    The NExT Program’s Chemical Biology Consortium (CBC) — contributes expertise to NExT projects to advance early-stage drug discovery projects

    Cleave Biosciences — performed initial drug development for one of the inhibitors and is a member of the CBC

    NCI’s Comparative Oncology Program, Center for Cancer Research — performed canine clinical trials of one of the inhibitors and continues to evaluate the treatment in pet dogs on a dose escalation trial

For more information on the NExT Program, read details on How to Apply, or contact NExT Program staff.