methoxyamine (TRC102) / Tracon Pharma - LARVOL DELTA

NCI-2021-14403: Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=42 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Large Cell Carcinoma • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4

Iron-Catalyzed Direct Synthesis of Amides from Alcohols. (PubMed, Org Lett) - "Herein, we report an iron-catalyzed, one-pot, direct synthesis of amides via dehydrogenative amidation of alcohols using methoxyamine hydrochloride as a nitrogen source. Enabled by a well-defined Fe(II) catalyst of a redox-active azo-phenanthroline ligand, the reaction proceeds via the cooperative participation of iron and the ligand, producing a broad spectrum of amides, including (hetero)aromatic and aliphatic amides, and complex bioactive amide molecules in good isolated yields."

Journal

Specific serum metabolites can differentiate severe and mild human traumatic brain injury. (PubMed, Clin Chim Acta) - "Our findings indicate that specific serum metabolites, particularly methoxyamine, may serve as novel biomarkers for differentiating severe from mild TBI. Further research is warranted to explore their potential as therapeutic targets and their role in TBI pathophysiology."

Journal • CNS Disorders • Metabolic Disorders • Vascular Neurology • CDC37 • HSP90AA1

One-Step Chemoenzymatic Labeling and Oxime-Reversible Enrichment for O-GlcNAcylation Profiling under Oxidative Stress. (PubMed, Anal Chem) - "Crucially, oxime-based capture using hydroxylamine-functionalized beads, followed by reversible methoxyamine-mediated release, overcomes the limitations of conventional ketone-based enrichment strategies and eliminates the need for azide-based chemistry...Functional studies suggested a potential role of O-GlcNAcylation in the nucleocytoplasmic redistribution of the chromatin remodeler EP400 during stress-granule assembly. This platform thus provides a powerful and versatile tool for advancing the O-GlcNAcylation research."

Journal • EP400

Characterizing the Reactive Metabolites of Colony-Stimulating Factor 1 Receptor Inhibitor PLX5622 in Liver Microsomes and Mice. (PubMed, Chem Res Toxicol) - "Reduced glutathione (GSH) and methoxyamine (NH2OMe) were used to capture reactive intermediates. These insights into the metabolic pathways of PLX5622 are valuable for further study of its safety and potential drug interactions of CYP3A. Future studies using human primary hepatocytes or physiologically human-relevant models such as liver-on-a-chip systems are warranted to confirm clinical relevance and better predict in vivo outcomes."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Selective Cytotoxicity of Base Excision Repair Inhibitor, TRC102, in DNA Damage Response Hyperactivated Glioblastoma (AACR 2026) - "Conclusions The antitumor effect of TRC102 appears to be mediated through targeting of the newly identified ATM-CHK2-HIF axis, allowing for selective cytotoxicity in DDR-hyperactivated glioblastoma. These results suggest a specific vulnerability to TRC102 in DDR-hyperactivated glioblastoma that are typically resistant to conventional chemotherapy and radiation therapy, supporting biomarker-driven patient selection in future clinical studies."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CHEK2

Investigation into oximation methods to improve the selective detection of small α-ketoacids in cell extracts by GC-EI-MS. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "We find that oximation using hydroxylamine, ethoxyamine, or O-benzylhydroxylamine offer comparable performance to methoxyamine with distinct effects on column retention and main fragment ion mass-to-charge. We also demonstrate how these approaches may be applied to cell extracts. Our results highlight hydroxylamine or O-benzylhydroxylamine as preferred derivatization reagents to increase alpha-ketoacid mass-to-charge or increase column retention, respectively."

Journal

Computational Repurposing and Experimental Validation of YBX1 Inhibitors in Hepatocellular Carcinoma. (PubMed, Biomedicines) - "Further literature review and feasibility assessment narrowed the list to six candidates: malonaldehyde, mercaptoethanol, glycine, para-chlorophenol, methoxyamine, and ethanolamine. These findings support YBX1 as a promising therapeutic target in hepatocellular carcinoma and demonstrate the utility of drug repurposing to rapidly identify candidate inhibitors. Targeting YBX1 may provide a viable strategy for enhancing treatment efficacy and overcoming sorafenib resistance in advanced HCC."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • Transplantation • YBX1

MOSCAT: Aldehyde-Selective Chemical Proteomics for Site-Specific Profiling of Cinnamaldehyde Targets in Living Cells. (PubMed, Anal Chem) - "Herein, we developed MOSCAT (MethOxyamine-enabled Site-specific Cinnamaldehyde Tagging), a probe-free chemical proteomic strategy for mapping cinnamaldehyde-targeted proteins in living cells...This modification triggers proteasome-mediated GPX4 degradation, identifying a specific covalent engagement site associated with CA-induced ferroptosis. Our findings demonstrate MOSCAT as a powerful platform for elucidating molecular mechanisms of electrophilic natural products and highlight GPX4 Cys93 as a promising druggable site for CA-based therapeutic interventions."

Journal • Oncology • GPX4

Deciphering glioblastoma heterogeneity: Integrating molecular signatures and genomic landscapes to predict drug sensitivity and advance precision oncology (SNO 2025) - "Comprehensive drug screening was performed on these models, evaluating agents such as temozolomide, arsenic trioxide (ATO), TRC102, pevonedistat, TAS4464, candesartan cilexetil, selinexor, GB13, DSP-0390, and the combination of ATO with a MNK1 inhibitor. Future research will focus on analyzing CNV changes and transcriptomic differential expression within patient data and validating drug efficacy on patient-derived tumor cultures. This comprehensive strategy aims to translate preclinical discoveries into clinically relevant biomarkers, ultimately paving the way for personalized and more effective GBM treatments."

Heterogeneity • Brain Cancer • Glioblastoma • Solid Tumor

Deciphering glioblastoma heterogeneity: Integrating molecular signatures and genomic landscapes to predict drug sensitivity and advance precision oncology (WFNOS 2025) - "Comprehensive drug screening was performed on these models, evaluating agents such as temozolomide, arsenic trioxide (ATO), TRC102, pevonedistat, TAS4464, candesartan cilexetil, selinexor, GB13, DSP-0390, and the combination of ATO with a MNK1 inhibitor. Future research will focus on analyzing CNV changes and transcriptomic differential expression within patient data and validating drug efficacy on patient-derived tumor cultures. This comprehensive strategy aims to translate preclinical discoveries into clinically relevant biomarkers, ultimately paving the way for personalized and more effective GBM treatments."

Heterogeneity • Brain Cancer • Glioblastoma • Glioma • Solid Tumor

Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

Repair of abasic site-derived covalent DNA adducts by formamidopyrimidine DNA glycosylase (FPG) (ACS-Fall 2025) - "Covalent capture of the reactive aldehyde form of AP sites by small molecules such as methoxyamine and hydralazine can inhibit APE1 activity, thereby blocking BER progression. Our studies employ gel electrophoresis to monitor repair activity and mass spectrometry to characterize the repair products. These findings suggest the existence of an alternative, APE1-independent pathway for the repair of AP-derived covalent adducts, with potential implications for BER pathway switching and cellular responses to DNA damage."

Comparability of different analytical workflows for steroid esters detection in doping control field. (PubMed, J Pharm Biomed Anal) - "For initial screening procedure, methanol and Girard's Reagent P or T (1.0 mg/mL in acetic acid/methanol/water 2:6:2, v:v:v, 30 min, 65 °C) are recommended (limits of detection: 0.5-1.0 ng/mL for boldenone esters; 0.05-0.50 ng/mL for the other esters). For confirmation, a compound-specific approach is suggested: methanol and methoxyamine (100 mM for 30 min, 70 °C) for boldenone esters, testosterone cypionate, enanthate and decanoate (limits of identification: 0.25-2.00 ng/mL), while Girard's Reagent P or T remains optimal for the other esters (limits of identification: 0.2-1.0 ng/mL)."

Journal

Design, Synthesis, and Insecticidal Activity of Sulfonamide Structures Containing Methoxyamine as Potential Inhibitors of V-ATPase. (PubMed, Chem Biodivers) - "Compound 5.3 was verified to act on ATPase as well through symptomological analysis and molecular docking. This study provided potential inhibitors of V-ATPase for the M. separata control."

Journal • CGN

NCI-2021-14403: Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Jun 2027 | Trial primary completion date: Dec 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Large Cell Carcinoma • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4

Analytical workflow for comprehensive blood metabolomics analysis by GC-MS. Application to children with ventilator associated pneumonia. (PubMed, J Chromatogr A) - "The method consists of a common two-step derivatisation procedure including methoximation using methoxyamine hydrochloride, followed by silylation with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA)...This analysis led to the identification of 43 metabolites. The results of multivariate and univariate statistical analyses demonstrated several statistically significant metabolites, including aspartic acid, alanine, and pyroglutamic acid, which showed a strong correlation with the disease's manifestation and may potentially serve as biomarkers in the diagnosis of ventilator-associated pneumonia VAP at the stage of clinical suspicion."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Total Synthesis of (-)-Vescalagin, the Iconic Member of the C-Glucosidic Ellagitannin Family. (PubMed, Chemistry) - "The first total synthesis of the 2,3,5-O-(S,R)-NonaHydroxyTriPhenoylated (NHTP) and 4,6-O-(S)-HexaHydroxy-DiPhenoylated (HHDP) C-glucosidic ellagitannin (-)-vescalagin was accomplished through a bioinspired route involving intramolecular atroposelective cupric-diamine complex-mediated phenolic couplings of gallates to forge its HHDP and NHTP units, and a methoxyamine-driven opening of a glucopyranose intermediate followed by a phenolic aldol-type reaction to form its C-arylglucosidic bond. The minor epimer that resulted from this bond-forming event was used to complete also a first total synthesis of the vescalagin epimer, (-)-castalagin."

Journal

Investigation of absorption, metabolism, and excretion of [14C]pruxelutamide (GT0918), an androgen receptor antagonist in humans. (PubMed, Br J Clin Pharmacol) - "Overall, all the dosed subjects completed the study, and GT0918 was found to be safe, with no grade II or above adverse events reported. A total dose of 82.81% was quantified in the urine (29.47%) and faeces (53.34%) of healthy adult male subjects after a single oral administration of 200 mg (80 μCi) GT0918 ([14C]GT0918). The metabolism of GT0918 is catalysed predominantly by CYP3A4, and an uncommon pathway of oxazole ring-opening to an aldehyde intermediate has also been proposed."

Journal • Infectious Disease • Novel Coronavirus Disease • CYP3A4

Bypass of Methoxyamine-Adducted Abasic Sites by Eukaryotic Translesion DNA Polymerases. (PubMed, Int J Mol Sci) - "On the contrary, Rev1 bypassed AP-MOX 5-fold better than the AP site. Together, our data suggest that Rev1 is best suited to support synthesis across AP-MOX in human cells."

Journal • Review • Oncology

Repurposing the Antihypertensive Agent Hydralazine As an Inhibitor of the Base Excision Repair Enzyme APE1. (PubMed, Chem Res Toxicol) - "Hydralazine was found to be superior to the investigational drug methoxyamine in its capacity to covalently capture AP sites in duplex DNA and inhibit the action of APE1. It was further shown that hydralazine sensitized SF295 glioblastoma cells to the cytotoxic action of the anticancer drug Temozolomide, which generates alkylpurine residues requiring APE1 for repair. The results suggest that the FDA-approved drug hydralazine might be repurposed in oncology to potentiate the activity of existing chemotherapeutic agents that induce AP sites in cellular DNA."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2024 ➔ Oct 2025

Combination therapy • Metastases • Surgery • Trial completion date • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

Base-excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma. (PubMed, Cell Rep) - "Co-treatment with ATR inhibitor (VX970) and BER inhibitor (methoxyamine) at clinically relevant doses synergistically enhanced DNA damage and reduced cell proliferation in PDAC cells. The study provides mechanistic insights into the regulation of TRCs in PDAC by the BER pathway, which has biologic and therapeutic implications."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Optimized high-throughput protocols for comprehensive metabolomic and lipidomic profiling of brain sample. (PubMed, Talanta) - "For GC-MS based metabolomics analysis, incubation time, temperature, and methoxyamine concentration (10 mg/mL) affected metabolite coverage significantly...In conclusion, DoE-based optimization strategies for a three-in-one single-step extraction enabled rapid, comprehensive, high-throughput, and simultaneous analysis of metabolites, lipids, and even proteins from a 10 mg brain sample. Under optimized conditions, 475 lipids and 158 metabolites were identified in brain samples."

Journal

A Phase 2 Randomized Study of the BER Inhibitor TRC102 in Combination with Standard Pemetrexed-Platinum-Radiation in Stage III Non-Squamous Non-Small Cell Lung Cancer (NCI 10512) (ASTRO 2024) - P2 | "We published our Phase I study of combining TRC102 with Pemetrexed-Cisplatin (Pem-Cis) and Thoracic RT (TRT) in stage III and oligometastatic stage IV adenocarcinoma... The 12-month PFS of NSCLC under chemo-radiation therapy followed by durvalumab (standard care) is about 56%... The study will collect pre-treatment biopsy specimen to test for UNG expression. The hypothesis is high level of UNG in the tumor causes resistance to Pem and addition of TRC102 will improve the efficacy of Pem."

Clinical • Combination therapy • P2 data • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • TYMS • UNG