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Pharmaprojects No. 3498

✓ Approved

Southern Research Institute · POLA1 · Small Molecule

What is Pharmaprojects No. 3498?

Pharmaprojects No. 3498 is a small molecule developed by Southern Research Institute. It is approved for therapeutic indications via unknown.

Drug Profile

CompanySouthern Research Institute
Drug ClassSmall Molecule
Molecular TargetPOLA1, POLB
RouteUnknown
StatusApproved
Sources: ClinicalTrials.gov, Southern Research Institute

Mechanism of Action

Molecular Targets

Pharmaprojects No. 3498 acts on 2 molecular targets:

POLA1DNA polymerase alpha 1, catalytic subunit (PDR, POLA)
POLBDNA polymerase beta ()
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

Pharmaprojects No. 3498 is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Hairy cell leukaemia✓ Approved

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PubMedInternational journal of molecular sciences2026-10-16

Multiomics Insights in Research of Nitric Oxide (NO) Donors in Plants upon Stress.

Gurina Anastasia A, Margarit Anna A, Zhikhreva Anastasia A, Frolova Nadezhda N et al.

It is known that the progressive climate changes and environmental pollution prevalent all over the world lead to increasingly frequent and prolonged episodes of stress, and it challenges plants to adapt to changing adverse conditions. Given the significant crop losses caused by challenging environments, protecting plants from the destructive effects of these factors has become one of the most pressing challenges in modern agricultural biology and plant physiology. One of the approaches to protect plants from stressors in modern agrobiotechnology is the use of nitric oxide (NO) donors, which are chemicals that can release NO in plant cells and stimulate their germination, growth, biomass accumulation, and protection against external factors. Studying their mechanism of action at the molecular level is essential for understanding the targets of NO action, as well as for developing new phytoeffectors. A multiomics approach, along with physiological data, is often the method of choice. In this review, we compare widely used NO donors (e.g., sodium nitroprusside, S-nitrosoglutathione, NONOates) in terms of chemical properties, NO-release kinetics, stability, and suitability for different application methods (seed treatment, foliar spray, root application). Finally, we highlight recent advances from proteomics, metabolomics, and transcriptomics that have enabled system-wide identification of NO-responsive pathways and candidate targets. By integrating physiological, biochemical, and multiomics data, this review provides a framework for understanding NO-mediated stress tolerance and for the rational design of new NO-based phytoeffectors.

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PubMedDalton transactions (Cambridge, England : 2003)2026-10-16

Comparative insights into transition metal mediated nitrite to nitric oxide conversion.

Meitei Naorem Jemes NJ, Chu Yu-Ting YT, Qiu Guo-Ge GG, Ibrahim Amjath Alikhan AA et al.

Nitrite (NO2-) is a widespread environmental pollutant that contributes to eutrophication, nitrosative stress, and N-nitrosamine formation. The chemical factors that make copper optimal for nitrite to NO conversion remain central to understanding copper nitrite reductase activity. Here, we compare ascorbate-driven nitrite reduction using transition-metal salts and synthesized ligand-supported Cu(II) complexes under identical aqueous conditions. CuCl2 shows the highest activity, producing NO quantitatively within 8 s with an initial NO-generation rate of 15.6 cm3 s-1 and a TOF of 45 000 h-1. The synthesized copper complexes, (en)CuCl2, DMEDACuCl2, and TMEDACuCl2, also demonstrate rapid NO formation, confirming that Cu(II)/Cu(I) cycling is the key catalytic platform. Importantly, the NO generation rate of the copper series generally follows the Cu(II)/Cu(I) reduction potential: complexes with more positive potentials show faster NO release, consistent with easier Cu(II) reduction and more efficient electron transfer to HNO2. TMEDACuCl2 deviates positively from this trend, suggesting additional ligand effects such as Cu(I) stabilization, altered coordination geometry, or improved substrate access. UV-vis spectroscopy, cyclic voltammetry, 15N-labeling FTIR, and (TPP)CoNO trapping support a Cu-centered proton-coupled electron-transfer pathway. In contrast, iron forms iron-nitrosyl species that decrease freely detectable NO and limit the effective turnover. These results establish copper as the optimal redox platform for fast nitrite-to-NO conversion.

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PubMedBiology2026-10-16

Cyanide Metabolism in Apple Embryos During Dormancy Breakage Is Modulated by NO or HCN Application.

Piekarniak Maciej Arkadiusz MA, Ciacka Katarzyna K, Gniazdowska Agnieszka A, Krasuska Urszula U

Hydrogen cyanide (HCN) is an N-containing gasotransmitter with a regulatory function in plants and animals. Despite its toxicity, HCN acts as a signalling molecule in plants, influencing development, pathogen defence, and stress responses, with particular emphasis on biotic stress and seed dormancy/germination. Around 3000 species across > 130 families produce HCN from cyanogenic compounds. This study investigated how nitric oxide (NO) and HCN impact the activity of enzymes involved in HCN metabolism during dormancy breakage of apple (Malus domestica Borkh.) embryos. Based on earlier findings that HCN exposure elevates NO emission and alters the phytoglobin-NO cycle, we examined whether NO affects HCN metabolism. We measured the activities of β-glucosidases, β-cyanoalanine synthase (β-CAS), and sulfurtransferases (STRs) (HCN-detoxifying enzymes), and the transcript levels of their corresponding gene homologues. Both NO and HCN stimulated β-glucosidase activity and enhanced β-CAS and STR activities. Although both N-containing gasotransmitters increased β-CAS transcripts, they differentially implicated transcript levels of STR homologues. Additionally, only HCN increased the transcript levels of mitochondrial cysteine synthase (OASTL-C). These results, together with our previous work, potentially link NO and HCN in the metabolic network during dormancy breakage of apple embryos.

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PubMedAnimals : an open access journal from MDPI2026-10-16

Bis(4-hydroxyphenyl) Sulfone Regulates Sperm Motility, Mitochondrial Activity, and Nitric Oxide Production in Boar Semen.

Lee Seunghyung S, Lee Sang-Hee SH

BPS is a substitute for bisphenol A, an endocrine disruptor. Our study aimed to evaluate the effects of BPS on sperm viability and motility, acrosomal membrane damage, mitochondrial activity, and NO production in boar semen. 0, 40.0, 80.0, and 100.0 μM BPS were treated in the boar semen. In the results, sperm viability did not change across any treatments. However, sperm motility was significantly decreased in the 100.0 μM BPS-treated groups (78.56%, p < 0.05) and progressive motility of sperm (60.24%, p < 0.05). Acrosomal membrane damage was not changed in the BPS-treated groups, but mitochondrial activity (58.85%, p < 0.05) of sperm was decreased in the 100.0 μM BPS-treated groups. The NO in the 100.0 μM BPS-treated sperm groups was increased (p < 0.05). Based on the results, we suggest that BPS elevates NO production, and the increased NO damages mitochondrial activity. Thus, BPS may directly regulate sperm motility, such as through oxidative stress.

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PubMedDiagnostics (Basel, Switzerland)2026-10-16

Can Routine Preoperative Endoscopy and Colonoscopy Be Meaningful for the Surgery and Postoperative Course of Patients with Advanced Ovarian Cancer? A Single-Centre Retrospective Cohort Study.

Doğan Göktürk Han GH, Akpınar Göksever G, Tutal Anıl Doğukan AD, Sağlam Purut Ceren C et al.

Background/Objectives: Bowel resection is often required for complete cytoreduction in advanced ovarian cancer, and some units perform upper gastrointestinal endoscopy and colonoscopy beforehand. We compared the endoscopic biopsy findings with the histopathology of the resected bowel and examined determinants of survival. Methods: Eighty-three consecutive women with FIGO stage III-IV serous ovarian cancer cytoreduced to no macroscopic residual disease between 2015 and 2021 were reviewed retrospectively; all had undergone both examinations and completed adjuvant carboplatin-paclitaxel. Results: Bowel resection was performed in 20 women (24.1%). Serosal involvement was reported in 15 specimens and no tumour in four; mucosal invasion was reported in none (95% CI 0-16.8%). Eighteen patients (21.7%) were biopsied endoscopically; no biopsy was malignant. Over a median follow-up of 72 months, 50 women (60.2%) developed recurrence (28 confirmed histologically and 22 diagnosed from imaging and CA-125; recurrence was ascertained retrospectively, which limits the interpretation of disease-free survival) and 44 (53.0%) died. Recurrence was no more frequent in biopsied than in non-biopsied patients (8/18 vs. 42/65, p = 0.174) or after resection (10/20 vs. 40/63, p = 0.306). Age showed an exploratory association with disease-free (HR 1.03/year, 95% CI 1.00-1.06) and overall survival (HR 1.04, 1.00-1.07). Conclusions: In this cohort, no preoperative endoscopic biopsy was malignant and no resected specimen was reported to show mucosal invasion, supporting a limited role for routine endoscopy in assessing bowel wall involvement; its diagnostic accuracy and its value for excluding a gastrointestinal primary could not be assessed.

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PubMedInternational journal of molecular sciences2026-10-16

Nitric Oxide Signaling in Photosynthetic Resilience: Linking Photoprotection and Carbon Gain in Tropical Crops.

Islam Mohammad Shafiqul MS, Methela Nusrat Jahan NJ, Cho Young B YB, Lee Moon-Sub MS et al.

Tropical crops are increasingly exposed to climate-driven, recurrent combinations of heat, excessive irradiance, high vapor pressure deficit (VPD), drought, flooding, salinity, and pathogen pressure that collectively impair photosynthesis and reduce crop productivity. Unlike individual stress events, these interacting stresses simultaneously disrupt photoprotection, electron transport, carbon assimilation, stomatal regulation, and chloroplast redox homeostasis, ultimately limiting whole-plant carbon gain under fluctuating environments. Nitric oxide (NO) has emerged as a central signaling molecule coordinating these adaptive responses, yet its roles in photosynthetic regulation remain dispersed across molecular, physiological, and crop-specific studies. This review presents an integrated framework linking chloroplast-level NO signaling with whole-plant photosynthetic performance in major tropical crops, including maize, sugarcane, banana, cassava, and oil palm. We propose that NO regulates photosynthetic resilience through three interconnected axes: (i) reversible protein S-nitrosylation that modulates photosynthetic complexes and Calvin-Benson cycle enzymes; (ii) maintenance of chloroplast redox homeostasis through coordinated reactive oxygen species (ROS) and reactive nitrogen species (RNS) signaling, antioxidant networks, and S-nitrosothiol metabolism; and (iii) ABA-mediated stomatal regulation that optimizes the trade-off between carbon assimilation, stomatal conductance, and water-use efficiency under environmental stress. We further discuss the emerging roles of S-nitrosothiols (SNOs) and S-nitrosoglutathione (GSNO) as central regulators of NO homeostasis and potential biochemical indicators linking chloroplast signaling with whole-plant carbon performance. By synthesizing current evidence across climate-relevant stress combinations, including heat + high light, drought + high VPD, flooding + hypoxia, salinity + pathogen interactions, this review provides a conceptual framework for understanding NO-mediated photosynthetic resilience and identifies key research priorities for developing NO-based strategies to enhance productivity and climate resilience in tropical cropping systems.

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