Identification and Development of Agents to Treat Glioblastoma and Other Tumors Over-expressing Nuclear Receptor CoRepressor

The National Institute of Neurological Disorders and Stroke (NINDS) and Lixte Biotechnology Holdings, Inc. (Lixte) are collaborating to identify and develop agents that target the Nuclear Receptor CoRepressor (N-COR) pathway. Dr. Zhengping Zhuang’s laboratory at NINDS has determined that several kinds of tumors, including glioblastomas and medulla blastomas, over-express N-CoR. 

Dr. Zhuang discussed this discovery with Dr. John S. Kovach shortly before Dr. Kovach decided to start a new biotechnology company. After the company, Lixte Biotechnology Holdings, Inc., was founded, a Cooperative Research and Development Agreement (CRADA) between NINDS and Lixte was executed to develop agents to treat glioblastoma. 

Lixte developed and provided agents to Dr. Zhuang so he could determine if the agents inhibited the growth of tumor cells growing in vitro. Several of the agents had the desired activity, and two, designated LB-100 and LB-102, were selected for further studies. LB-100 and LB-102 are also effective inhibiting the growth of the tumor cells in a mouse model of glioblastoma (growth of a human glioblastoma tumor injected into mice). Preliminary studies indicate that LB-102 might be used in combination with other cancer chemotherapeutics to treat patients with glioblastoma multiforme, neuroblastoma, and other cancers. Lixte and NINDS have conducted preliminary toxicity studies and pharmacokinetic studies on LB-102. Lixte plans to continue these studies and hopes to submit an IND to the FDA for treatment of patients with glioblastoma multiforme in the near future. 

Patents related to the treatment on central nervous systems cancers (such as glioblastomas and medulloblastomas) with some of the agents studied in the CRADA were filed, and Lixte has licensed NINDS’ rights to these patents. 

Awardee

National Institute of Neurological Disorders and Stroke

• Dr. Zhengping Zhuang