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Next-generation broad-spectrum anti-cancer Rad51 inhibitors

Technology Benefits

§ Mode of action for the Rad51 inhibitor, predicted via in silico modeling studies, has been independently validated via in vitro studies, and provides a robust mechanistic platform for developing it as an anti-cancer drug § Efficacy against multiple types of cancer cell lines § Other analogs may serve as anti-cancer drugs for other types of cancers

Detailed Technology Description

In 2012, an estimated 14.1 million new cases of cancer occurred worldwide, with 8.1 million deaths. In the US alone, in 2013, ~233K were diagnosed with breast cancer, of which >~41K died (~17.5% mortality rate). The human burden and financial costs (direct and indirect) of cancer is very high, and are expected to increase as human lifespan is extended by medical innovation. It is estimated that there will be 23.6 million new cases of cancer worldwide each year by 2030. As a key player in homologous recombination, the RAD51 recombinase is essential for DNA repair, cell proliferation and survival, and is therefore critical for cancer survival and proliferation. This invention describes the design, synthesis and evaluation of a panel of 24 new RAD51 inhibitors that are analogs of a previously described synthetic alkaloid - IBR2, shown to inhibit Rad51 both in vitro and in vivo. One of these analogs effectively inhibits triple negative breast cancer, which is often resistant to existing therapeutics, and also inhibits the proliferation of a broad spectrum of other cancer cell types. Furthermore, this molecule was shown in assays to disrupt RAD51 multimerization, impair homologous recombination repair, and induce apoptotic cell death, and is therefore a potential candidate for development as a broad-spectrum anti-cancer pharmaceutical drug.

Application No.

20180057483

Others

State Of Development

• In vitro studies of cell lines for human chronic myelogenous leukemia, triple-negative breast cancer, osteosarcoma, glioblastoma, and cervical cancer show significant growth inhibition. A difference of up to 10X in IC50 was observed between non-cancer and cancer (3~5 μM) cells, suggesting little to no side-effects from chemotherapy in human patients
• Mode of action for inhibition of Rad51 recombinase activity and multimerization, predicted by molecular modeling, has been independently confirmed via experimental assays.

Related Materials

Zhu, J.; Chen, H.; Guo, X. E.; Qiu, X.-L.; Hu, C.-M.; Chamberlin, A. R.; Lee, W.-H. European Journal of Medicinal Chemistry 2015, 96, 196–208.

Tech ID/UC Case

27368/2015-222-0

Related Cases

2015-222-0

*Abstract

This invention describes the design, synthesis and successful evaluation of a panel of novel Rad51 inhibitors to treat a broad spectrum of cancer types.

*IP Issue Date

Mar 1, 2018

*Principal Investigator

Name: Hongyuan Chen

Department:

Name: Xuning Guo

Department:

Name: Wen Hwa Lee

Department:

Name: Xia-Long Qui

Department:

Name: Jiewen Zhu

Department:

Country/Region

USA