New Targeted Therapy for Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia


The invention describes the use of benzodiazepine compounds for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Specifically, the compounds can be used to treat core binding factor (CBF) leukemias, which are a subgroup of leukemia associated with the generation of fusion genes, arising from the binding between the transcription factors: core binding factor-beta (CBFbeta) and runt-related transcription factor 1 (RUNX1). The compounds described in this invention have been found to inhibit the binding of CBFbeta and RUNX1, resulting in selectively killing leukemia cells in culture and suppressing leukemia in a mouse model.

In addition, the binding of runt-related transcription factors from the RUNX family have been implicated in the development of other diseases, including (but not limited to): platelet disorders, solid tumours (e.g., lymphoma, breast cancer, osteosarcoma) and bone diseases (e.g., osteoporosis, cleidocranial dysplasia and intervertebral disk degeneration). Thus, the use of these compounds may represent new targeted therapies for AML and ALL as well as other RUNX-related disorders.

Potential Commercial Applications: Competitive Advantages:
  • Targeted drug therapies for AML and ALL.
  • Combination chemotherapies for AML and ALL.
  • Therapies for other RUNX related disorders, including platelet disorders, solid tumours (e.g., lymphoma, breast cancer, osteosarcoma) and bone diseases (e.g., osteoporosis, cleidocranial dysplasia and intervertebral disk degeneration).
 
  • Proof of concept demonstrated in a mouse model.
  • Compounds have been previously tested in clinical studies for anti-HIV drugs.


Development Stage:
  • Early-stage
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:

Pu Liu (NHGRI)  ➽ more inventions...

Wei Zheng (NCATS)  ➽ more inventions...

Juan Marugan (NCATS)  ➽ more inventions...

Noel Southall (NCATS)  ➽ more inventions...

Lea Cunningham (NCI)  ➽ more inventions...


Intellectual Property:
US Pat: 9,446,048 issued 2016-09-20
PCT Application No. PCT/US2012/029169 filed on 2012-03-15
US Application No. 14/005,534 filed on 2013-09-16

Publications:
Cunningham L, et al. PMID 22912405

Collaboration Opportunity:

The National Human Genome Research Institute (NHGRI), Oncogenesis and Development Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize benzodiazepine compounds described above to treat CBF leukemia, AML, ALL, and/or other RUNX-related disorders. Please contact Claire T. Driscoll, Director of NHGRI Technology Transfer Office (cdriscoll@mail.nih.gov; 301-594-2235) for more information.


Licensing Contact:
Eggerton Campbell, Ph.D.
Email: eggerton.campbell@nih.gov
Phone: 301-402-1648

OTT Reference No: E-060-2011-0
Updated: Sep 10, 2012