Publications

Prabhu et al. ONC201 and imipridones: Anti-cancer compounds with clinical efficacy. Neoplasia 2020 December doi: 10.1016/j.neo.2020.09.005

Arillaga-Romany et al. Biological activity of weekly ONC201 in adult recurrent glioblastoma patients. Neuro Oncology 2020 doi: 10.1093/neuonc/noz/164

Stein et al. Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration. Journal for ImmunoTherapy of Cancer 2019.

Romaguera et al. Integrated stress response and immune cell infiltration in an ibrutinib-refractory mantle cell lymphoma patient following ONC201 treatment British Journal of Haematology, 2018.

Stein et al. First-in-human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors Clinical Cancer Research 2017 Mar 22 doi:10.1158/1078-0432.CCR-16-2658.

Bruzek et al. Electronic DNA Analysis of CSF Cell-free Tumor DNA to Quantify Multi-gene Molecular Response in Pediatric High-grade Glioma. Clinical Cancer Research 2020 October 21 doi: 10.1158/1078-0432.CCR-20-2066

Wierzbicki et al. Targeting and Therapeutic Monitoring of H3 K27M-Mutant Glioma. Current Oncology Reports Feb:6 (2020) doi:10.1007/s11912-020-0877-0

Hall et al. First clinical experience with DRD2/3 antagonist ONC201 in H3 K27M-mutant pediatric diffuse intrinsic pontine glioma: a case report. Journal of Neurosurgery, 2019.

Chi et al. Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201 Journal of Neuro-Oncology, 2019.

14. TRAIL-Inducing Small Molecule ONC201 Prevents Intestinal Tumors in FAP Mouse Model.
June 22, 2020, 9:00AM

Combinatorial Activity:
1836. ONC201 Shows Synergistic Effect with the Androgen Receptor (AR) Inhibitor Darotulamide in Prostate Cancer Model.
June 22, 2020, 9:00AM

4808. ONC201 Decreases Protein Chaperone ClpX to Unleash Mitochondrial Protease ClpP Activity, Integrated Stress Response and Tumor Cell Death.
June 22, 2020, 9:00AM

3012. Novel Small Molecule ONC201 Induces Apoptosis in Gastric Adenocarcinoma and Exhibits Synergy with rhTRAIL.
June 22, 2020, 9:00AM

5407. Novel Imipridone Combination Therapies Targeting Oncohistone H3 K27M-Mutant Diffuse Midline Glioma (DMG).
June 22, 2020, 9:00AM

4042. Potent Synergistic Tumor Cell Suppression from Combination of ONC201 and Epigenetic Modulators EZH2 or HDAC Inhibitors Provides a Novel Treatment Strategy for Solid Tumors.
June 22, 2020, 9:00AM

3902. Novel Therapeutic Targeting of Epigenetic Aberrations in Pediatric Sarcomas through Combination of ONC201 and HDAC Inhibitors.
June 22, 2020, 9:00AM

5260. Preclinical Studies with ONC201 in Combination with Clinically Approved Chemotherapy as a Novel Treatment Strategy Against Small Cell Lung Cancer (SCLC).
June 22, 2020, 9:00AM

3904. The Novel Combination of PAC-1 and ONC201 Circumvent H3K27M-Driven Pro-Survival Gene Expression to Induce DIPG Cell Death.
June 22, 2020, 9:00AM

ONC201 Clinical Translation:
TBD Immuno-modulatory Activity of Selective DRD2 Antagonist ONC201, an Imipridone, in Metastatic Endometrial Cancer (mEC).
Date and time TBD

ONC201 Mechanism and Biomarkers:
3173. Predictive Biomarker Evaluation for the Anti-Cancer Imipridone ONC201.
June 22, 2020, 9:00AM.

4794. Mitochondrial Matrix Protease ClpP Agonists Inhibit Cell Growth and Cancer Stem Cell Function in Breast Cancer Cells.
June 22, 2020, 9:00AM

ONC206:
5688. IND-Enabling Characterization of ONC206 as the Next Bitopic DRD2 Antagonist for Neuro-oncology.
June 24, 2020, 9:00AM

5314. A Novel Dopamine Receptor D2 Antagonist (ONC206) Potentiates the Effects of Olaparib in Endometrial Cancer Cells through Inhibition of Cell Proliferation and Modulation of the mTOR Pathway.
June 22, 2020, 9:00AM

3797. Investigating the Anti-Cancer Effects of Novel Dopamine Receptor D2 Antagonists in a Panel of Human Cancer Cell Lines.
June 22, 2020, 9:00AM

5321. Novel Imipridone ONC206 Inhibits Cell Proliferation and Induces Apoptosis in Uterine Serous Cancer through Altering MAPK/AKT Signaling Network and Metabolic Reprogramming
June 22, 2020, 9:00AM

5336. Olaparib Potentiates the Anti-Proliferative and Anti-Metastatic Effects of ONC206 in Ovarian Cancer Cells.
June 22, 2020, 9:00AM

2958. ONC206, an Imipridone Derivative, Induces Cell Death through Activation of the Integrated Stress Response in Serous Endometrial Cancer In Vitro.
June 22, 2020, 9:00AM

ONC212:
6225. Addition of TRAIL Receptor Antagonists after Treatment with ONC201 or ONC212 Converts Pancreatic Cancer Cells from Anti-Proliferative to Apoptotic In Vitro.
June 22, 2020, 9:00AM

612. ONC212 Affects ClpXP Complex, Impairs Mitochondrial Bioenergetics and Synergizes with Glycolysis Inhibition in Pancreatic Cancer.
June 22, 2020, 9:00AM

1286 / 1 – ONC201 inhibits RET and IGFBP2 signaling through ATF4 mediated- Integrated stress response in medullary thyroid cancer

249 / 12 – Combination of ONC201 with radiation exhibits synergistic efficacy in high grade gliomas and other advanced cancers

5183 / 1 – ONC201 induces acetylation of histone binding within the p21 (CDKN1A) gene promoter

2664 / 18 – Differential activation of the integrated stress response correlates with anti-tumor activity of imipridones ONC201 and ONC206 in pediatric sarcomas

4808 / 22 – Preclinical studies of the combination of ONC201, radiotherapy and Temozolomide against GBM, DIPG and ATRT cell lines

2928 / 16 – New insight into signaling contexts for the administration of the imipridone ONC201 to prostate cancer cells

364 / 25 – The dopamine receptor D2 antagonist ONC201 has anti-tumorigenic activity in obesity-driven epithelial ovarian cancer

258 / 2 – Recombinant human TRAIL or a DR5 agonistic antibody convert the response of non-triple negative breast cancer cells to ONC201 from anti-proliferative to apoptotic

262 / 6 – Anti-tumorigenic effect of ONC201 is enhanced by combination treatment with TRAIL or a DR5 agonist in endometrial cancer in vitroNeuro-Tumor Club – Selective targeting of dopamine receptor dysregulation in high grade gliomas with imipridone ONC201

Imipridone GPCR SAR:

2749 / 1 – Defining structure activity relationships for GPCR engagement and anti-cancer efficacy of imipridone small molecules

ONC206:

3877 / 27 – IND-enabling characterization of DRD2/3 imipridone antagonist ONC206 for oncology

Oral Talks:

2720 – Mitochondrial ClpP-mediated proteolysis induces selective cancer cell lethality

Neuro-Tumor Club – IND-enabling characterization of DRD2/3 imipridone antagonist ONC206 for oncology

ONC201 Clinical Translation:

(3857) Prabhu et al. Selective targeting of dopamine receptor dysregulation in high grade gliomas with imipridone ONC201, April 17, 2018, 8:00 AM

(4872) Proudfit et al. ONC201 induction of apoptosis in hPheo1 cell line supports use of this oral agent in ongoing phase 2 clinical trial against neuroendocrine tumors, April 17, 2018, 1:00 PM

(5568) Tarapore et al. Clinical immunostimulatory activity of imipridone ONC201, a selective DRD2 antagonist, in advanced solid tumor patients, April 18, 2018, 8:00 AM

ONC201 Preclinical Single Agent and Combinatorial Activity

(839) Amoroso et al. Treatment and signaling contexts for the application of the imipridone ONC201 to prostate cancer cells, April 15, 2018, 1:00 PM

(LB-082) Ralff et al. ONC201 sensitizes resistant breast cancer cells to TRAIL through death receptor 5 upregulation, April 16, 2018, 8:00 AM – 12:00 PM

(2933) Zhou et al. Synergistic antitumor effect of ONC201 in combination with radiation therapy, April 16, 2018, 1:00 PM

(2765) Jhawar et al. Combination ONC201 and radiation therapy in the treatment of breast cancer, April 16, 2018, 1:00 PM

Analogs (ONC206 and ONC212):

(4874) Prabhu et al. Receptor pharmacology and anti-cancer activity of selective DRD2/3 antagonist imipridone ONC206, April 17, 2018, 1:00 PM

(4957) The novel imipridone ONC212 highly synergizes with the BCL-2 inhibitor ABT-199 in AML and activates orphan receptor GPR132 April 17, 2018, 3:35 PM – Oral Presentation

Madhukar et al. Differentiated receptor pharmacology of imipridone ONC201: the first DRD2 antagonist in clinical development for oncology 2017 AACR April 1-5 Washington DC

Madhukar et al. The small molecule imipridone ONC201 is active in tumor types with dysregulation of the DRD2 pathway 2017 AACR April 1-5 Washington DC

Klein et al. Antagonism of D2-like dopamine receptors plays a role in ONC201’s anti-cancer effects 2017 AACR April 1-5 Washington DC

Lim et al. Preclinical evaluation of imipridone ONC201 in triple negative breast cancer identifies predictive biomarkers and combinatorial opportunities 2017 AACR April 1-5 Washington DC

Prabhu et al. Potent anti-cancer effects of selective GPR132/G2A agonist imipridone ONC212 in leukemia and lymphoma 2017 AACR April 1-5 Washington DC

Prabhu et al. Potent anti-cancer activity of the imipridone ONC206: A selective dopamine D2-like receptor antagonist 2017 AACR April 1-5 Washington DC

Wagner et al. Preclinical evaluation of the imipridone family of small molecules, including analogues of clinical-stage anti-cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212 2017 AACR April 1-5 Washington DC

Lev et al. Anti-cancer efficacy of imipridones in pancreatic cancer: single agent ONC212 or combination of ONC201 with IGF1-R inhibition 2017 AACR April 1-5 Washington DC

Tu et al. Imipridone ONC201 efficacy in refractory multiple myeloma via Erk1/2 inhibition and pro-apoptotic Bim upregulation: Single agent and combinatorial approaches 2017 AACR April 1-5 Washington DC

Wagner et al. Imipridone ONC201 promotes intra-tumoral accumulation of CD3+/NK+ cells that contribute to its anti-tumor efficacy 2017 AACR April 1-5 Washington DC

Greer et al. ONC201 kills breast cancer cells by inhibiting mitochondrial respiration 2017 AACR April 1-5 Washington DC

Amoroso et al. Modulating the UPR using the imipridone ONC201 to change the impact of radiation on prostate cancer cells. 2017 AACR April 1-5 Washington DC

Lev et al. ONC201 targets AR and AR-V7 signaling pathways, reduces PSA and synergizes with everolimus in castration resistant prostate cancer 2017 AACR April 1-5 Washington DC

Baumeister et al. ONC201 efficacy in BRCA-deficient cancer cells and synergy with PARP inhibitors in glioblastoma, breast, prostate, and ovarian cancers 2017 AACR April 1-5 Washington DC

Wagner et al. Anti-tumor effects of imipridone ONC201 in combination with anti-angiogenic agents significantly impact on colorectal cancer growth in vivo 2017 AACR April 1-5 Washington DC

Madhukar et al. D2-like dopamine receptor antagonism by ONC201 identified by confluence of computational, receptor binding, and clinical studies 2016 AACR –Apr. 17 – Apr. 20; New Orleans, LA.

Lev, El-Deiry et al. ONC201 induces cell death in androgen receptor positive prostate cancer cells and shows synergistic effect with anti-prostate cancer drugs 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Prabhu et al. ONC201 targets cancer stem cells in colorectal, prostate and glioblastoma multiforme tumors via modulation of stem cell-related gene expression 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Tarapore at al. ONC201 sensitivity profiling indicates pronounced sensitivity in lymphoid, prostate, colon and brain tumors 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Lev, El-Deiry et al. ONC212 exhibits increased cytotoxicity relative to ONC201 in a subset of human pancreatic cancer cell lines 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Wagner, El- Deiry et al. Structure-activity relationships and mechanistic analysis of analogues of the clinical-stage anti-cancer small molecule ONC201 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Wagner, El-Deiry et al. Intra-tumoral accumulation of NK1.1/CD3+ cells and anti-metastisis effects of dose-intensified ONC201 in tumor-bearing mice 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Baumeister, El-Deiry et al. ONC201 induces cell death in triple negative, BRCA1-deficient and non-triple negative breast cancer cells 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Kline, El-Deiry et al. ONC201 anti-cancer effects against solid tumors are mediated through elF2α kinases HRI and PKR but are PERK-independent  2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Baumeister, El-Deiry et al. Novel small molecule ONC201 induces cell death and targets chemotherapy-resistant cancer stem-like cells in triple negative breast cancer 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Wagner, El-Deiry et al. Combination of ONC201 and bevacizumab significantly impacts colorectal cancer growth and metastasis in vivo 2016 AACR — Apr. 17 – Apr. 20; New Orleans, LA.

Baumeister et al. Novel small molecule ONC201 induces cell death in triple negative and non-triple negative breast cancer cells. 2015 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference — Nov5 – Nov9; Boston, MA.

Stein et al. First-in-human dose escalation study of oral ONC201 in advanced solid tumors. 2015 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference — Nov5 – Nov9; Boston, MA.

Allen et al. The small molecule TIC10 has potent anticancer efficacy mediated by induction of TRAIL production in normal and tumor cells.
AACR 106th Annual Meeting 2015‐‐ Apr 18-22, 2015; Philadelphia, PA.

Allen et al. ONC201 is non-toxic at efficacious doses in vitro and in vivo.
AACR 106th Annual Meeting 2015‐‐ Apr 18-22, 2015; Philadelphia, PA.

Kline et al. Early integrated stress response induction of ATF4 is required for the anticancer effects of the dual Akt/ERK inhibitor and TRAIL pathway inducer ONC201/TIC10.
AACR 106th Annual Meeting 2015‐‐ Apr 18-22, 2015; Philadelphia, PA.

Kline et al. TRAIL pathway inducer ONC201/TIC10 primes multiple myeloma cells (MM) for apoptosis by downregulating X-linked inhibitor of apoptosis.
AACR 106th Annual Meeting 2015‐‐ Apr 18-22, 2015; Philadelphia, PA.

Prabhu et al. ONC201/TIC10 targets colorectal cancer stem cells and bulk tumor cells via an Akt-Foxo3a-TRAIL-dependent mechanism.
AACR 106th Annual Meeting 2015‐‐ Apr 18-22, 2015; Philadelphia, PA.

Talekar et al. ONC201/TIC10 is effective as a monoagent and synergizes with chemotherapy to induce cell death in non-Hodgkin’s lymphoma.
AACR 106th Annual Meeting 2015‐‐ Apr 18-22, 2015; Philadelphia, PA.

Wagner et al. Cytotoxicity, Biochemical Activity, and Structural Analysis of ONC201 Clinical Material and Comparisons to a Biologically Inactive Isomer.
AACR 106th Annual Meeting 2015‐‐ Apr 18-22, 2015; Philadelphia, PA.

Imperato et al. Characterization of TIC10, a novel small molecule inducer of TRAIL, in combination with chemotherapy for lymphoma in vitro.
AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC.

Talekar et al. TRAIL-inducing agent -TIC10 and combinatorial therapeutics in pediatric lymphoma: a targeted approach.
AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC.

Prabhu et al. Therapeutic targeting of colorectal cancer stem cells by TRAIL-inducing small molecule TIC10.
AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC.

Allen et al. Kinase library siRNA screen identifies KSR1 as a synergistic therapeutic target in combination with TIC10.
AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC.

Allen et al. Potent anti-tumor effects of TIC10 require Foxo3a and TRAIL gene upregulation.
AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL.

Allen et al. The small molecule TIC10 has potent anticancer efficacy mediated by induction of TRAIL production in normal and tumor cells.
AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL.

Schalop and Allen GPCRs, Desirable Therapeutic Targets in Oncology
Drug Discovery and Development 2017 Jan.

Bar-Shavit et al. G-Protein Coupled Receptors in Cancer
International Journal of Molecular Sciences 2016, 17(8), 1320; doi:10.3390/ijms17081320

Liu et al. G protein coupled receptors as promising cancer targets.
Cancer Letters 2016 Jul 1;376(2):226-39

Insel et al. G Protein–Coupled Receptor (GPCR) Expression in Native Cells: “Novel” endoGPCRs as Physiologic Regulators and Therapeutic Targets.
Mol Pharmacol. 2015 Jul; 88(1): 181–187

O’Hayre et al. The emerging mutational landscape of G proteins and G-protein-coupled receptors in cancer.
Nat Rev Cancer. 2013 Jun;13(6):412-24

Lappano et al. G protein-coupled receptors: novel targets for drug discovery in cancer.
Nat Rev Drug Discov. 2011 Jan;10(1):47-60

Gutkind et al. G-protein-coupled receptors and cancer.
Nat Rev Cancer. 2007 Feb;7(2):79-94.

Dirks et al. Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells. Cancer Cell. 2016 Jun 13;29(6):859-873. doi: 10.1016/j.ccell.2016.05.002.

Li et al. Paired related homeobox 1 transactivates dopamine D2 receptor to maintain propagation and tumorigenicity of glioma-initiating cells. J Mol Cell Biol. 2017 Aug 1;9(4):302-314. doi: 10.1093/jmcb/mjx017.

Caragher SP, et al. Activation of dopamine receptor 2 (DRD2) prompts transcriptomic and metabolic plasticity in glioblastoma. Neuro Oncol. 2019 Jan 16. pii: 1589-18. doi: 10.1523/JNEUROSCI.1589-18.2018

Schalop et al. The Role of DRD2 in Cancer
Drug Discovery and Development 2016 Aug.

Caragher SP, et al. Monoamines in glioblastoma: complex biology with therapeutic potential Neuro Oncol. 2018 Jul 5;20(8):1014-1025. doi: 10.1093/neuonc/nox210

Studies indicating differentiated dopamine receptor expression in human cancers

Studies indicating anti-tumor efficacy of DRD2 antagonists in preclinical models