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New Targeted Therapy for Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia

Posted Sep 09 2012 8:00pm

Description of Invention:
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.

Applications:
  • 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).


Advantages:
  • Proof of concept demonstrated in a mouse model.
  • Compounds have been previously tested in clinical studies for anti-HIV drugs.


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


Inventors:
Pu Liu (NHGRI)
Wei Zheng (NCATS)
Juan J Marugan (NCATS)
Noel T Southall (NCATS)
Lea C Cunningham (NCI)


Patent Status:
HHS, Reference No. E-060-2011/0
PCT, Application No. PCT/US2012/29169 filed 15 Mar 2012


Relevant Publication:
  1. Cunningham L, et al. [ PMID 22912405 ]


Collaborative Research 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.


For Licensing Information Please Contact:
Sabarni Chatterjee Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: chatterjeesa@mail.nih.gov
Phone: 301-435-5587
Fax: 301-402-0220


Ref No: 2477

Updated: 09/2012

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