Two distinct late stage preclinical lead series of highly specific inhibitors of MAP4K4

Reference number 8377, 8717, 10459, 10460

Sectors: Pharmaceuticals

Industries: Cardiovascular

A late-stage, pre-clinically validated inhibitor of MAP4K4 for a range of indications including anthracycline cardiotoxicity

Proposed use

Anthracycline chemotherapy leads to acute cardiotoxicity in up to 30% of patients. The MAP4K4 inhibitors can be commercialized to be used for protective agents against anthracycline therapy-induced cardiotoxicity.

Additionally, MAP4K4 is a pivotal mediator of a number of key pathways and a target in a range of clinical applications with significant unmet need. These targets include:

  • Neurodegeneration
  • Vascular disease
  • Cancer (including glioblastoma)
  • Anti-tumour and antiviral immunity
  • Autoimmune disorders including diabetes

Technology overview

  • Novel, potent, highly-selective, non-toxic inhibitors
  • Protection against anthracycline therapy validated in human and rat cardiomyocytes.
  • Good inhibitors of MAP4K4 with DMPK work undertaken
  • Range of assays focused on developing highly-specific MAP4K4 inhibitor targeting ATP-binding pocket
  • Multiple screen cascade/in vivo and in vitro validation of target and pre-lead candidates
  • Encouraging safety profile with no adverse effect on cloned human channels
  • Growing excitement in targeting MAP4K4 for other clinical applications

 Benefits

  • The compounds inhibit MAP4K4 in the low-mid nanomolar range
  • Pre-clinically validated protection against anthracycline cardiotoxicity
  • Demonstrated safety in murine and porcine models
  • MAP4K4 an attractive target in other indications

Intellectual property information

This technology is protected by a family of patents covering composition of matter and use  of two distinct chemical series number WO2018035563A1 and number WO2019073253A1.

Inventor

Professor Michael Schneider

Chair in Cardiology
Faculty of Medicine, National Heart & Lung Institute

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Contact us about this technology

8377 - contact

Contact

Stephanie Morris

Director of Industry Partnerships and Commercialisation, Medicine

Stephanie Morris is Director of Industry Partnerships and Commercialisation for the Faculty of Medicine at Imperial College London.

Contact Stephanie

+44 (0)20 7594 2717

stephanie.morris@imperial.ac.uk

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