Evidence map›Paper›PMID 40082968›Full record

ArticleMolecular cancer2025

ADT-1004: a first-in-class, oral pan-RAS inhibitor with robust antitumor activity in preclinical models of pancreatic ductal adenocarcinoma.

Dhana Sekhar Reddy Bandi, Ganji Purnachandra Nagaraju, Sujith Sarvesh, Julienne L Carstens, Jeremy B Foote, Emily C Graff, Yu-Hua D Fang, Adam B Keeton, Xi Chen, Jacob Valiyaveettil and 12 more

Abstract read
In one paragraph

Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Efficacy of dual KRASCell death & disease · 2026
    Article
  7. Article
  8. KRAS Inhibitors in Pancreas Cancer: Facts and Hopes about the Immunotherapy We Have All Been Waiting for.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  9. KRAS Inhibition in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2026
    Review
  10. Review
  11. Key Considerations for TargetingDrug design, development and therapy · 2026
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Dhana Sekhar Reddy BandiDepartment of Hematology and Oncology, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama, Birmingham, AL, 35233, USA.
Ganji Purnachandra NagarajuDepartment of Hematology and Oncology, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama, Birmingham, AL, 35233, USA.
Sujith SarveshDepartment of Hematology and Oncology, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama, Birmingham, AL, 35233, USA.
Julienne L CarstensDepartment of Hematology and Oncology, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama, Birmingham, AL, 35233, USA.
Jeremy B FooteDepartment of Microbiology, University of Alabama, Birmingham, AL, 35294, USA.
Emily C GraffDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, 36849, USA.
Yu-Hua D FangRadiology and Neurology, University of Alabama, Birmingham, AL, 35233, USA.
Adam B KeetonDrug Discovery and Development Department, Harrison College of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
Xi ChenDrug Discovery and Development Department, Harrison College of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
Jacob ValiyaveettilDrug Discovery and Development Department, Harrison College of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
Kristy L BerryDrug Discovery and Development Department, Harrison College of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
Sejong BaeDivision of General Internal Medicine and Population Science, University of Alabama School of Medicine, Birmingham, AL, 35233, USA.
Mehmet AkceDepartment of Hematology and Oncology, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama, Birmingham, AL, 35233, USA.
Greg GormanDepartment of Pharmaceutical, Social and Administrative Sciences, Samford University, Birmingham, AL, 35229, USA.
Karina J YoonDepartment of Pharmacology and Toxicology, University of Alabama, Birmingham, AL, 35233, USA.
Upender ManneDepartment of Pathology, University of Alabama, Birmingham, AL, 35233, USA.
Michael R BoydADT Pharmaceuticals, LLC, Orange Beach, AL, 31691, USA.
Donald J BuchsbaumDepartment of Obstetrics and Gynecology, University of Alabama, Birmingham, AL, 35233, USA.
Asfar S AzmiDepartment of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Yulia Y MaxuitenkoDrug Discovery and Development Department, Harrison College of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
Gary A PiazzaDrug Discovery and Development Department, Harrison College of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
Bassel F El-RayesDepartment of Hematology and Oncology, O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama, Birmingham, AL, 35233, USA. belrayes@uabmc.edu.

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
Exploiting the immunomodulatory effects of sulindac and novel non-COX inhibitory derivatives for cancer treatmentR01CA238514 · NCI · AUGUSTA UNIVERSITY · PI PIAZZA, GARY A, ZHOU, GANG · 2020 to 2024
$2.1M
Novel inhibitor for oncogenic RAS for lung cancerR01CA254197 · NCI · AUBURN UNIVERSITY AT AUBURN · PI PIAZZA, GARY A · 2021 to 2025
$1.9M
ProAgio in Pancreatic CancerR01CA294647 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Bassel El-Rayes, Zhi-Ren Liu · 2024 to 2026
$1.7M
Multi-parameter, analytic flow cytometerS10OD032296 · OD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI RANDALL, TROY D · 2022 to 2022
$464k
Auburn University P30CA01314NCI NIH HHS P30 CA013148NCI NIH HHS R01 CA238514NCI NIH HHS R01 CA254197NCI NIH HHS R01 CA294647NIH HHS 1R01CA294647NIH HHS NIH/NCI R01CA254197NIH HHS S10 OD032296University of Alabama at Birmingham, Birmingham, Oneal Comprehensive Cancer Centre 5P30CAO13148-47
6 · The paper itself

Abstract

backgroundOncogenic KRAS mutations occur in nearly, 90% of patients with pancreatic ductal adenocarcinoma (PDAC). Targeting KRAS has been complicated by mutational heterogeneity and rapid resistance. We developed a novel pan-RAS inhibitor, ADT-1004 (an oral prodrug of ADT-007) and evaluated antitumor activity in murine and human PDAC models. METHODOLOGY: Murine PDAC cells with KRAS

resultsADT-1004 potently blocked tumor growth and RAS activation in mouse PDAC models without discernable toxicity with target engagement and reduced activated RAS and ERK phosphorylation. In addition, ADT-1004 suppressed tumor growth in PDX PDAC models with KRAS CONCLUSION/SIGNIFICANCE: ADT-1004 has strong antitumor activity in aggressive and clinically relevant PDAC models with unique selectivity to block RAS-mediated signaling in RAS mutant cells. As a pan-RAS inhibitor, ADT-1004 has broad activity and potential efficacy advantages over allele-specific KRAS inhibitors. These findings support clinical trials of ADT-1004 for KRAS mutant PDAC.

Indexed as

Antineoplastic AgentsCarcinoma, Pancreatic DuctalPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorCell ProliferationDisease Models, AnimalHumansMiceMutationXenograft Model Antitumor AssaysAntineoplastic AgentsProto-Oncogene Proteins p21(ras)KRASPancreatic ductal adenocarcinomapan-RAS inhibitorRAS-driven malignanciesTumor immune microenvironment

Identifiers

PMID40082968
PMCPMC11905721

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Registered trials

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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.