Fenoterol and Fenoterol Analogues for Treatment of Glioma, Glioblastoma, and Astrocytoma

To date there is no effective treatment for the brain tumors or brain cancers indentified as gliomas, glioblastomas, or astrocytomas.

This technology relates to the discovery that fenoterol and related analogues block astrocytoma and glioblastoma cell division at low doses. In a xenograft model utilizing the 1321N1 astrocytoma tumor implanted in the flank of SKID mice, the (R,R)-4-methoxyfenoterol analogue significantly decreased tumor growth relative to a control group receiving vehicle and studies utilizing [3H]-(R,R)-4-methoxyfenoterol have shown that the compound readily passes the blood-brain barrier. The anti-tumor effect is associated with the ability of fenoterol and related analogues to induce production of cyclic adenosine monophosphate (cAMP), which is normally decreased in glioblastomas and astrocytomas. Induced cAMP production inhibits brain tumor growth in vivo. Fenoterol and related analogues are beta-2 adrenergic receptor (beta2 AR) agonists and the anti-tumor effect is associated with the expression of this receptor. Since there is a heterogeneous expression of beta2 AR in human brain tumors, patients who will respond to fenoterol therapy can be predetermined leading to individualized treatment. In addition to use in the initial treatment of brain tumors, the systemic and CNS bioavailability of the drug after oral administration and the minimal systemic toxicity suggest that fenoterol and it analogs can be used in the adjuvant treatment of patients with beta2 AR-positive gliomas, glioblastomas or astrocytomas. Studies with a number of fenoterol analogs and CNS-implanted tumors are in progress.

The fenoterol analogues discussed in this technology are subject to HHS Ref. No. E-205-2006/2 (US Patent No. 8,703,826).

Potential Commercial Applications: Competitive Advantages:
  • Therapeutic in the front line and adjuvant treatment of glioma, glioblastoma and astrocytoma.
  • Potential first-in-class therapeutic for multiple types of brain tumors.

Development Stage:
In vivo: tumor models in SKID mice. In vitro: cell-based assays using human glioblastoma and astrocytoma cell lines. Further in vivo studies in animal models are underway.


Irving Wainer (NIA)  ➽ more inventions...

Intellectual Property:
U.S. Pat: 9,492,405 issued 2016-11-15
US Application No. 61/312,642
PCT Application No. PCT/US2011/027988
US Application No. 13/583,206
US Application No. 16/129,470

Collaboration Opportunity:

The National Institute on Aging, Laboratory of Clinical Investigation, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of fenoterol and fenoterol analogs in the front line and adjuvant treatment of CNS tumors and other beta2 AR expressing tumors. Please contact Nikki Darack Guyton, Ph.D. at 240-276-5493 or guytonn@mail.nih.gov for more information.

Licensing Contact:
Richard Girards, J.D., M.B.A.
Email: richard.girards@nih.gov
Phone: 240-276-6825

OTT Reference No: E-013-2010-0
Updated: Jun 6, 2018