HJF scientists have developed a first-in-class family of novel and potent small molecule ERG inhibitors that can be used as targeted therapeutics for malignant diseases with overexpression of ERG oncoproteins. Therapeutic indications may include prostate cancer, leukemia, and colorectal cancer.

Applications and Advantages

• First-in-class small molecule inhibitors of ERG oncoprotein with a nanomolar level of IC₅₀
• Composition of matter patents and patent applications for the compounds
• Targeted therapeutics for prostate cancer, leukemia, colorectal cancer, and Kaposiform hemangioendothelioma

Innovation Description

Prostate Cancer is among the leading causes of cancer related death of men in the United States. Overexpression of ERG transcripts and proteins represents most prevalent (50-65%) prostate cancer driver alterations. The ERG oncoprotein overexpression persists in approximately 35% of metastatic castration resistant prostate cancers. In addition, aggressive forms of acute myeloid leukemia (AML), colorectal carcinoma (CRC), and Kaposiform hemangioendothelioma are also have ERG oncoprotein overexpression.

HJF scientists have developed three generations of small molecule ERG inhibitors, including a family of salt derivatives, for specifically targeting ERG harboring cancer cells. Results of in vitro studies have shown that these ERG inhibitors exhibit nanomolar levels of IC ₅₀ in inhibiting tumor cell growth. Procedures for the synthesis of these small molecule inhibitors are also available.

ERGi-USU-6 Salt derivative . (A) compound 7b inhibits the growth of ERG positive VCaP cells. (B) compound 7b is a potent inhibitor of ERG and RIOK2 proteins. (C,D,E) compound 7b showed improved cell growth, ERG protein, and RIOK2 proteins inhibitory with IC₅₀ of 0.089µM, 0.17µM and 0.13 µM, respectively.

Inventors

• Albert Dobi, Ph.D. HJF
• Sanjay Malhotra, Ph.D. Oregon Health & Science University
• Mallesh Pandrala, Ph.D. Oregon Health & Science University

Innovation Status

A family of small molecules, including a variety of salt derivatives, of ERG inhibitors have been synthesized. In vitro studies have validated their efficacy in inhibiting tumor cell growth.

Intellectual Property Status

Patents have been issued on the 1^st-generation compounds in the U.S. (9,782,394), Japan (6630285), Great Britain (3116954), France (3116954), Germany (3116954), South Africa (2016/06332), Australia (2015229379), and in Canada (2,942,485).

Patents have been issued on the 2^nd-generation compounds in the U.S. (10,238,639 and 11,648,239), France (3347001), Germany (3347001), Japan (6865174), Canada (2,981,188), and Australia (2016319111).

Patent applications on the 3^rd-generation compounds are pending in the United States, Canada, and Europe.

Publication

Binil Eldhose, Mallesh Pandrala, Charles Xavier et al. (2021) New Selective Inhibitors of ERG Positive Prostate Cancer: ERGi-USU-6 Salt Derivatives. ACS Med Chem Lett. 12(11): 1703–1709 .