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Staley A, Tucker K, Yin Y, et al. Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer. Am J Cancer Res. 2021;11(11):5374-5387
Staley, A., Tucker, K., Yin, Y., Zhang, X., Fan, Y., Zhang, Y., Fang, Z., Sun, W., Suo, H., Zhao, X., Zhao, Z., Prabhu, V. V., Allen, J. E., Zhou, C., & Bae-Jump, V. L. (2021). Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer. American journal of cancer research, 11(11), 5374-5387.
Staley, Allison, et al. "Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer." American journal of cancer research vol. 11,11 (2021): 5374-5387.
Staley A, Tucker K, Yin Y, Zhang X, Fan Y, Zhang Y, Fang Z, Sun W, Suo H, Zhao X, Zhao Z, Prabhu VV, Allen JE, Zhou C, Bae-Jump VL. Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer. Am J Cancer Res. 2021 Nov 15;11(11):5374-5387. eCollection 2021. PMID: 34873466; PMCID: PMC8640798.
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Am J Cancer Res. 2021 Nov 15;11(11):5374-5387. eCollection 2021.

Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer.

American journal of cancer research

Allison Staley, Katherine Tucker, Yajie Yin, Xin Zhang, Yali Fan, Yingao Zhang, Ziwei Fang, Wenchuan Sun, Hongyan Suo, Xiaoling Zhao, Ziyi Zhao, Varun Vijay Prabhu, Joshua E Allen, Chunxiao Zhou, Victoria L Bae-Jump

Affiliations

  1. Division of Gynecologic Oncology, University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.
  2. Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing 100069, China.
  3. Chimerix Durham, NC 27713, USA.
  4. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill Chapel Hill, NC 27599, USA.

PMID: 34873466 PMCID: PMC8640798

Abstract

Endometrial cancer (EC) is a highly obesity-driven cancer, with limited treatment options. ONC201 is an imipridone that selectively antagonizes the G protein-coupled receptors dopamine receptor D2 and D3 (DRD2/3) and activates human mitochondrial caseinolytic protease P (ClpP). It is a promising first-in-class small molecule that has been reported to have anti-neoplastic activity in various types of cancer through induction of the integrated stress response (ISR) as well as through stimulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and subsequent induction of apoptosis. ONC201 is being evaluated in Phase II clinical trials for solid tumors and hematological malignancies, including EC. ONC206 is an analog of ONC201 with nanomolar potency in Phase I clinical trials. This study evaluated the anti-tumor efficacy of ONC206 in EC cell lines and the

AJCR Copyright © 2021.

Keywords: ONC206; apoptosis; dopamine receptors; endometrial cancer; obesity

Conflict of interest statement

VVP and JEA are employees and stockholders of Oncoceutics/Chimerix. Dr. Bae-Jump’s laboratory received ONC201 and ONC206 from Oncoceutics/Chimerix for these studies. No potential conflicts of interest

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