methoxyamine (TRC102) / Tracon Pharma - LARVOL DELTA

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

Uncovering a facile, gram-scale synthesis of an unnatural amino acid: A gateway to the chemoselective neoglycosylation of synthetic peptides (ACS-Fall 2024) - "Our goal is to identify an efficient and scalable synthetic pathway to an unnatural amino acid with a methoxyamine side chain...Subsequent deprotection of the side chain will yield a free amine suitable for chemoselective glycosylation that does not require global protection of the saccharide substrate. This newfound accessibility will enable exploration of a wide array of peptides and neoglycopeptides, lending to improved characterization of structure to function relationships, and, consequently, the discovery of novel therapeutics, antibody-drug conjugates, and antimicrobial peptides"

A single-center, randomized, double-blind, placebo, parallel-controlled clinical study of Jinfei Zhisu Powder in the treatment of cough after cold pathogenic pulmonary infection (ChiCTR) - P=N/A | N=66 | Not yet recruiting | Sponsor: Xiyuan Hospital, China Academy of Chinese Medical Sciences; Xiyuan Hospital, China Academy of Chinese Medical Sciences

New trial • Cough • Infectious Disease • Respiratory Diseases

Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT. (PubMed, Clin Cancer Res) - P2 | "These findings confirm safety and feasibility of TRC102+TMZ for rGBM patients. They also warrant further evaluation of combination therapy in biomarker-enriched trials enrolling GBM patients with baseline hyperactivated DDR pathways."

Journal • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • PCNA

TRACON Announces Publication in Clinical Cancer Research of Phase 2 Clinical Data for TRC102, a DNA Damage Repair Inhibitor, in Recurrent Glioblastoma Patients (GlobeNewswire) - P2 | N=20 | NCT02395692 | "TRACON Pharmaceuticals...announced the publication of Phase 2 clinical data of its DNA damage repair inhibitor drug candidate, TRC102, in patients with glioblastoma in Clinical Cancer Research....Extended survival was observed in two patients (progression-free survival ≥ 17 months and overall survival > 32 months), both of whom demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability, and cellular proliferation by RNA sequencing prior to initiating treatment with Temodar and TRC102."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Rh(III)-Catalyzed C-H Activation/Annulation for the Construction of Quinolizinones and Indolizines. (PubMed, Org Lett) - "More especially, this transformation has successfully fulfilled a C-H bond activation of terminal olefin from enamides followed by a [3 + 3] and a [2 + 3] cyclization cascade under different catalytic conditions, respectively, to provide two kinds of potentially biologically active heterocyclic scaffolds with a ring-junction nitrogen atom. Mechanistically, the methoxyamine formyl group serves as either a traceless directing group (DG) or an oxidizing DG via the C-N and C-C cleavage in this protocol."

Journal

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) | Phase classification: P2 ➔ P1/2

Combination therapy • Metastases • Phase classification • Surgery • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

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) | N=78 ➔ 42

Combination therapy • Enrollment change • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4

Exceptional Responders to Base Excision Repair (BER) Inhibition for Recurrent Glioblastoma Display Enrichment for DNA Damage Response Pathways: RNA Sequencing Analysis from a Multicenter Trial (SNO 2023) - "TRC102 (methoxyamine), a small molecule DNA base-excision repair (BER) inhibitor, reverses temozolomide (TMZ) resistance in preclinical glioma models...If sufficient activity was identified, arm 2 was planned in bevacizumab-refractory patients... rGBM patients with elevated levels of MPG and DDR molecular signature may have impaired BER and respond better to TRC102+TMZ."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • MGMT • PCNA

Exceptional Responders to Base Excision Repair (BER) Inhibition for Recurrent Glioblastoma Display Enrichment for DNA Damage Response Pathways: RNA Sequencing Analysis from a Multicenter Trial (SNO 2023) - "TRC102 (methoxyamine), a small molecule DNA base-excision repair (BER) inhibitor, reverses temozolomide (TMZ) resistance in preclinical glioma models...If sufficient activity was identified, arm 2 was planned in bevacizumab-refractory patients... rGBM patients with elevated levels of MPG and DDR molecular signature may have impaired BER and respond better to TRC102+TMZ."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • MGMT • PCNA