PR104 / Proacta - LARVOL DELTA

Inhibition of thermal formation of advanced glycation end products and acrylamide by gluten-bound betulonic acid and alphitolic acid: Mechanistic insights from spectroscopy and computation. (PubMed, Food Res Int) - "Molecular dynamics simulations further corroborated AA's binding stability within the gluten matrix, characterized by sustained interactions localized at residues Pro104, Tyr94, and Gln98. Collectively, these results delineate a mechanism whereby AA, by modulating gluten structure and potentiating its antioxidative defense system, effectively mitigates the formation of deleterious compounds in thermally processed foods, thereby advancing natural strategies for enhancing food safety and nutritional integrity."

Journal

Peritumoral Hyperlucency Might Be A Novel Marker For Predicting Breast Cancer Prognosis (EUSOBI 2025) - "Hormone receptor positivity rates of the cases were ER 103 (82%), PR 104 (84%), HER2/neu 20 (17%), Ki-67 54 (45%)...Presence of PH might be used as a novel simple marker to predict the prognosis of breast cancer. However, large-scale studies are needed on this subject."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

THE EPIDEMIOLOGY OF ESOPHAGEAL CANCER IN ACHALASIA; A LARGE POPULATION BASED NATIONAL STUDY. (DDW 2022) - "This increased prevalence of esophageal cancer in patients with achalasia was present when patients were stratified by age (Adults PR 26.6 (21.0-33.6), p<0.001; Elderly PR 7.21 (6.17-8.41), p<0.001); race (Caucasian PR 13.3 (11.6-15.3), p<0.001; African American PR 104.6 (73.1-150), p<0.001), and gender (Male PR 3.68 (3.15-4.30), p<0.001; Female PR 21.7 (17.4-27.0), p<0.001)...Surveillance endoscopies for patients with achalasia remains controversial. Our data supports continued surveillance given the significant elevated risk of development of esophageal cancer in those patients."

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Immunology • Inflammation • Oncology • Rare Diseases

Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling. (PubMed, Front Pharmacol) - "In the present study, we investigate the pharmacological properties of the nitrogen mustard prodrug CP-506 in tumour tissues using in silico spatially-resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) modelling...Our simulations predict a striking bystander efficiency at tissue-like densities with the bis-chloro-mustard amine metabolite (CP-506M-Cl) identified as a major diffusible metabolite. Overall, this study shows that CP-506 has favourable pharmacological properties in tumour tissue and supports its ongoing development for use in the treatment of patients with advanced solid malignancies."

Journal • PK/PD data • Oncology • Solid Tumor

Restoring Tumour Selectivity of the Bioreductive Prodrug PR-104 by Developing an Analogue Resistant to Aerobic Metabolism by Human Aldo-Keto Reductase 1C3. (PubMed, Pharmaceuticals (Basel)) - "We confirmed that SN29176 was not a substrate for AKR1C3 orthologues across all four pre-clinical species, demonstrating that this prodrug analogue class is suitable for further development. Based on these findings, a prodrug candidate was subsequently identified for clinical trials."

Journal • Oncology • AKR1C3

Bioreductive prodrug PR-104 improves the tumour distribution and titre of the nitroreductase-armed oncolytic adenovirus ONYX-411 leading to therapeutic benefit. (PubMed, Cancer Gene Ther) - "The combination of ONYX-411 with PR-104 was efficacious against HCT116 xenografts, whilst neither prodrug nor virus were active as single agents. This work highlights the potential for future clinical development of NTR-armed oncolytic viruses in combination with bioreductive prodrugs."

IO biomarker • Journal • Oncolytic virus • Infectious Disease • Oncology

Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy. (PubMed, Front Oncol) - "Both single-agent and combined use with other drugs have shown promising antitumor effects. In this review, we discuss the mechanism of action and the current preclinical and clinical progress of several of the most widely used HAPs, summarize their existing problems and shortcomings, and discuss future research prospects."

Review • Oncology • Solid Tumor

Use of an optimised enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumours. (PubMed, Cancer Gene Ther) - "Chemical induction of necrosis in human H1299 xenografts by the vascular disrupting agent vadimezan promoted colonisation by NmeNTR-expressing C. sporogenes, and efficacy studies demonstrated moderate but significant anti-tumour activity of spores when compared to untreated controls. Inclusion of the pre-prodrug PR-104 into the treatment schedule provided significant additional activity, indicating proof-of-principle. Successful preclinical evaluation of a transferable gene that enables metabolism of both PET imaging agents (for vector visualisation) and prodrugs (for conditional enhancement of efficacy) is an important step towards the prospect of CDEPT entering clinical evaluation."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

E. coli nitroreductase NfsA is a reporter gene for non-invasive PET imaging in cancer gene therapy applications. (PubMed, Theranostics) - "EF5 retention correlated with NfsA_Ec positive cell density over a range of EF5 concentrations in 3D in vitro models and in xenografts in vivo and was predictive of in vivo anti-tumor activity of the cytotoxic prodrug PR-104. Following PET imaging with F-HX4, a significantly higher tumor-to-blood ratio was observed in two xenograft models for NfsA_Ec expressing tumors compared to the parental tumors thereof, providing verification of this reporter gene imaging approach. This study establishes that the bacterial nitroreductase NfsA_Ec can be utilized as an imaging capable reporter gene, with the ability to metabolize and trap 2-nitroimidazole PET imaging agents for non-invasive imaging of gene expression."

Journal • Gene Therapies • Oncology

A phase I trial of PR-104, a pre-prodrug of the bioreductive prodrug PR-104A, given weekly to solid tumour patients (BMC Cancer) - P1, N=26; Thrombocytopenia, and to a lesser extent neutropenia, was the DLT of weekly PR-104. The MTD was 675 mg/m2/week

P1 data • Melanoma