Evidence map›Paper›PMID 33142238›Full record

ReviewNeoplasia (New York, N.Y.)2020

ONC201 and imipridones: Anti-cancer compounds with clinical efficacy.

Varun Vijay Prabhu, Sara Morrow, Abed Rahman Kawakibi, Lanlan Zhou, Marie Ralff, Jocelyn Ray, Aakash Jhaveri, Isacco Ferrarini, Young Lee, Cassandra Parker and 18 more

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neoplasia (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 163 citations in OpenAlex.

  1. Trial
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  4. Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
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53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 3 institutions in 1 country.

Varun Vijay PrabhuOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA.
Sara MorrowOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA.
Abed Rahman KawakibiOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA.
Lanlan ZhouWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Marie RalffFox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Jocelyn RayFox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Aakash JhaveriWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Isacco FerrariniWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Young LeeWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Cassandra ParkerWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Yiqun ZhangWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Robyn BorsukWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Wen-I ChangWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Joshua N HoneymanWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Fabio TavoraWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Benedito CarneiroWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Alexander RaufiWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Kelsey HuntingtonWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Lindsey CarlsenWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Anna LouieWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Howard SafranWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Attila A SeyhanWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA.
Rohinton S TaraporeOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA.
Lee SchalopOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA.
Martin StogniewOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA.
Joshua E AllenOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA. Electronic address: josh.allen@oncoceutics.com.
Wolfgang OsterOncoceutics, Inc., 3675 Market St, Suite 200, Philadelphia, PA 19104, USA.
Wafik S El-DeiryWarren Alpert Medical School, Brown University, 70 Ship Street, Room 537, Providence, RI 02912, USA. Electronic address: wafik@brown.edu.
Brown University · USOncoceutics (United States) · USFox Chase Cancer Center · US

Funding

TIC10 anti-tumor effect through regulation of Foxo3a and TRAILR01CA173453 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI EL-DEIRY, WAFIK S. · 2013 to 2023
$4.3M
TRAIL Upregulation by TIC10 AnalogsR43CA177002 · NCI · PROVID PHARMACEUTICALS, INC · PI EL-DEIRY, WAFIK S., OLSON, GARY L · 2014 to 2014
$225k
NCI NIH HHS R01 CA173453NCI NIH HHS R43 CA177002
6 · The paper itself

Abstract

ONC201 was originally discovered as TNF-Related Apoptosis Inducing Ligand (TRAIL)-inducing compound TIC10. ONC201 appears to act as a selective antagonist of the G protein coupled receptor (GPCR) dopamine receptor D2 (DRD2), and as an allosteric agonist of mitochondrial protease caseinolytic protease P (ClpP). Downstream of target engagement, ONC201 activates the ATF4/CHOP-mediated integrated stress response leading to TRAIL/Death Receptor 5 (DR5) activation, inhibits oxidative phosphorylation via c-myc, and inactivates Akt/ERK signaling in tumor cells. This typically results in DR5/TRAIL-mediated apoptosis of tumor cells; however, DR5/TRAIL-independent apoptosis, cell cycle arrest, or antiproliferative effects also occur. The effects of ONC201 extend beyond bulk tumor cells to include cancer stem cells, cancer associated fibroblasts and immune cells within the tumor microenvironment that can contribute to its efficacy. ONC201 is orally administered, crosses the intact blood brain barrier, and is under evaluation in clinical trials in patients with advanced solid tumors and hematological malignancies. ONC201 has single agent clinical activity in tumor types that are enriched for DRD2 and/or ClpP expression including specific subtypes of high-grade glioma, endometrial cancer, prostate cancer, mantle cell lymphoma, and adrenal tumors. Synergy with radiation, chemotherapy, targeted therapy and immune-checkpoint agents has been identified in preclinical models and is being evaluated in clinical trials. Structure-activity relationships based on the core pharmacophore of ONC201, termed the imipridone scaffold, revealed novel potent compounds that are being developed. Imipridones represent a novel approach to therapeutically target previously undruggable GPCRs, ClpP, and innate immune pathways in oncology.

Indexed as

AnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsClinical Studies as TopicClinical Trials as TopicDisease SusceptibilityDrug Evaluation, PreclinicalEndopeptidase ClpGene Expression Regulation, NeoplasticHumansImidazolesMitochondriaNeoplasmsNeoplastic Stem CellsPyridinesPyrimidinesAntineoplastic AgentsEndopeptidase ClpImidazolesPyridinesPyrimidinesReceptors, G-Protein-CoupledTIC10 compoundTNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID33142238
PMCPMC7588802
OpenAlexW3093671722

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.