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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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PubMedBMC oral health2026-08-30

Influence of high-power light-curing modes on the mechanical and optical properties of no-cap bulk-fill resin composites.

Kurucu Karadeni̇z Betül Kübra BK, Kütük Ömeroğlu Merve M

The clinical performance of no-cap bulk-fill resin composites depends strongly on adequate polymerization, which influences both mechanical durability and optical stability. Although contemporary high-power light-curing units (LCUs) provide ultra-fast curing modes, evidence regarding their effects on modern bulk-fill materials remains limited. This in vitro study aimed to evaluate the influence of different polymerization modes of VALO and Bluephase PowerCure on the microhardness and color stability of no-cap bulk-fill resin composites. Four no-cap bulk-fill resin composites (Omnichroma Bulk Flow, Charisma Bulk Flow ONE, Simplishade Bulk Fill, and Admira Fusion x-tra) were investigated. Two hundred cylindrical specimens (3 mm thickness) were prepared and polymerized using two LCUs (VALO and Bluephase PowerCure) under five curing modes (VALO Standard, High Power, and Xtra; Bluephase High Power and PowerCure). Vickers microhardness was measured on the top and bottom surfaces after 24 h, and bottom-to-top hardness ratios were calculated as an indicator of depth of cure. Baseline color was recorded and remeasured after 12-day coffee immersion at 37 °C, and color change (ΔE₀₀) was calculated. Data were analyzed using two-way ANOVA and Aligned Rank Transform ANOVA (α = 0.05). Composite type, polymerization mode, and their interaction significantly affected bottom-to-top hardness ratio, microhardness, and color change values (p < 0.001). VALO Standard and VALO High Power generally produced higher bottom-to-top hardness ratios and bottom-surface microhardness values than the 3-second ultra-short curing modes. Admira Fusion x-tra and Simplishade Bulk Fill generally showed higher microhardness values and/or lower ΔE₀₀ values under the tested conditions, whereas Omnichroma Bulk Flow and Charisma Bulk Flow ONE showed lower bottom-to-top hardness ratios or higher ΔE₀₀ values in some ultra-short curing groups. No consistent correlation was observed between ΔE₀₀ and bottom-to-top hardness ratio across the tested material-curing mode combinations. Polymerization mode and total radiant exposure influenced the mechanical and optical outcomes of the tested no-cap bulk-fill resin composites. Longer exposure protocols with higher radiant exposure generally resulted in more favorable bottom-to-top hardness ratios and bottom-surface microhardness values than the 3-second ultra-short curing protocols. The findings suggest that ultra-rapid curing modes may not provide equivalent outcomes for all no-cap bulk-fill resin composites. Therefore, curing protocols should be selected with consideration of material-specific behavior, exposure time, and total radiant exposure.

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PubMedLancet (London, England)2026-08-30

Discontinuation of β-blockers in stable patients with previous myocardial infarction, preserved left ventricular ejection fraction, and no heart failure: a pooled analysis of individual patient data.

Silvain Johanne J, Choi Ki Hong KH, Monguillon Victorien V, Kang Danbee D et al.

Many stable patients with chronic coronary syndrome continue β-blocker therapy for years after a myocardial infarction, despite having no clear ongoing indication. Whether β-blockers can be safely discontinued in such patients remains uncertain. The objective of this analysis was to assess the non-inferiority of β-blocker discontinuation versus continuation in patients with previous myocardial infarction and no remaining indication. We performed a pooled analysis of individual patient data from the ABYSS and SMART-DECISION randomised trials in stable patients over 6 months after a myocardial infarction with a left ventricular ejection fraction of ≥40% and no heart failure. Non-inferiority was assessed for the composite primary endpoint of all-cause death, myocardial infarction, stroke, or hospitalisation for cardiovascular reasons, and for the key secondary endpoint of all-cause death, myocardial infarction, or hospitalisation for heart failure. Analyses used a one-stage mixed-effects Cox proportional hazards model including trial as a random effect with margins of 1·25 for the primary endpoint and 1·40 for the key secondary endpoint. The review protocol was registered with PROSPERO, number CRD420261299839. Among 6238 patients (3698 from ABYSS and 2540 from SMART-DECISION), 3092 were assigned to β-blocker discontinuation and 3146 to continuation. Median time from index myocardial infarction to randomisation was 3·6 years (IQR 1·6-7·5) and median follow-up was 3·0 years (2·3-3·8). The primary endpoint occurred in 532 (17·2%) of 3092 patients in the β-blocker discontinuation group and 500 (15·9%) of 3146 in the continuation group (hazard ratio 1·09 [95% CI 0·97-1·24]; pnon-inferiority=0·016). The key secondary endpoint occurred in 201 (6·5%) of 3092 patients in the discontinuation group and 201 (6·4%) of 3146 patients in the continuation group (1·01 [0·83-1·23]; pnon-inferiority=0·0006). Findings were consistent irrespective of background left ventricular ejection fraction. In stable patients with previous myocardial infarction, left ventricular ejection fraction ≥40%, no heart failure, and no other indication for β-blocker therapy, discontinuation met the non-inferiority criteria for the primary and key secondary endpoints. Interpretation of the primary endpoint is limited by its hospitalisation-heavy and trial-dependent composition. None.

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Air Pollution Impairs Marathon Performance: A Cross-Sectional Analysis of 2.7 Million Finishers Across Six World Marathon Majors.

Donaldson James A JA, Cai Samuel S, Hey Josh Vande JV, Hansell Anna L AL et al.

Ambient air pollution impairs respiratory and cardiovascular function during exercise, yet evidence on its effects across the full spectrum of endurance performance remains limited. To quantify the association between race-day ambient air pollution and marathon finishing time across six World Marathon Majors, and to determine whether effects vary by sex, age group, and performance level. We analysed 2,756,553 net finishing times from six World Marathon Majors (Berlin, Boston, Chicago, London, New York City, and Tokyo) for editions held between 2010 and 2024. Race-day nitrogen dioxide (NO₂) and fine particulate matter (PM₂.₅) concentrations were obtained from the Copernicus Atmosphere Monitoring Service (CAMS) global reanalysis dataset. Linear mixed-effects models with random intercepts for each of 75 marathon-year events estimated pollution effects on finishing time, adjusting for heat index, wind speed, and temporal trends. Stratified analyses were conducted among 1,815,188 runners with available age data. Of the pollutants examined, NO₂ showed the stronger association with finishing time. Each 1 µg/m3 increase was associated with 1.43 min slower finishing time in men (95% confidence interval [CI] 0.66 to 2.21) and 1.56 min in women (95% CI 0.63 to 2.48). PM₂.₅ effects were not statistically significant: -0.13 min per µg/m3 in men (95% CI -0.67 to 0.40) and -0.14 min per µg/m3 in women (95% CI -0.76 to 0.49). Recreational runners experienced NO₂ effects approximately six-fold larger than elite runners (2.12 vs 0.34 min per µg/m3); expressed as a percentage of mean finishing time, this gradient persisted (0.67% vs 0.18%). Younger runners (18-29 years) showed larger effects than older runners (2.17 vs 1.32 min per µg/m3 for ≥60 years). Kolmogorov-Smirnov tests confirmed that higher NO₂ was associated with rightward shifts across the entire finishing time distribution. Ambient air pollution, particularly NO₂, is associated with impaired marathon performance in a dose-dependent manner, with the largest effects among recreational runners. These findings have implications for race management and public health policy regarding outdoor physical activity in urban environments.

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PubMedPakistan journal of medical sciences2026-08-30

Risk of heart failure in patients with schizophrenia or bipolar disorder: A systematic review and meta-analysis.

Dong Qifeng Q, Ye Xing X

Individuals with schizophrenia and bipolar disorder experience excess cardiovascular morbidity and premature mortality; however, the specific risk of incident heart failure has not been comprehensively quantified. We conducted a systematic review and meta-analysis to evaluate the risk of heart failure in these populations. A search was conducted on PubMed, Embase, Scopus, and Web of Science databases from inception through February 10, 2026, with no language restrictions, for cohort studies that reported adjusted estimates of the risk of incident heart failure in patients with schizophrenia or bipolar disorder. Random-effects meta-analyses were performed to obtain risk ratio (RR). Heterogeneity was assessed using the I² statistic. Seven retrospective cohort studies met the inclusion criteria. Schizophrenia was associated with a significantly increased risk of incident heart failure (RR: 1.50, 95% CI 1.35-1.67; I² = 74.9%). Bipolar disorder was associated with an even greater risk (RR: 1.95, 95% CI 1.31-2.91; I² = 80.1%). Sensitivity analyses confirmed the robustness of pooled estimates. Both schizophrenia and bipolar disorder are independently associated with substantially elevated risks of incident heart failure. High heterogeneity in the meta-analysis warrants caution in interpreting the results.Registration No: PROSPERO (No. CRD420261303975).

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Antidepressant initiation after sublingual immunotherapy in Japanese cedar pollinosis: a real-world propensity score-matched cohort study.

Matsushita Rie R, Tanaka-Mizuno Sachiko S, Kawakami Koji K

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PubMedPakistan journal of medical sciences2026-08-30

Diagnostic value of platelet-lymphocyte ratio for pediatric sepsis: A systematic review and meta-analysis.

Chen Li L, Yang Qiuping Q

Early diagnosis of pediatric sepsis remains challenging due to limitations of conventional biomarkers. The platelet-to-lymphocyte ratio (PLR), derived from routine blood tests, has emerged as a potential diagnostic marker. This study aimed to evaluate the diagnostic accuracy of PLR for pediatric sepsis. A systematic search of PubMed, Embase, Web of Science, and Scopus was conducted from inception to March 15, 2026. Studies assessing the diagnostic performance of PLR in pediatric sepsis and reporting sufficient data to construct 2×2 contingency tables were included. Pooled sensitivity and specificity were calculated using a random-effects model. Summary receiver operating characteristic (SROC) analysis and Deeks' funnel plot were performed. Fifteen studies with 1,980 patients were included. The pooled sensitivity and specificity of PLR for diagnosing pediatric sepsis were 0.81 (95% CI: 0.73-0.87) and 0.72 (95% CI: 0.60-0.82), respectively. The SROC curve demonstrated an area under the curve of 0.79, indicating moderate diagnostic accuracy. Significant heterogeneity was observed. Subgroup analysis showed better performance in larger studies (≥150 patients) and studies using higher PLR cut-offs (>50). Deeks' funnel plot showed no evidence of publication bias (p = 0.536). Evidence from studies with high-risk of bias indicates that PLR may have moderate diagnostic accuracy for pediatric sepsis and may serve as a simple, cost-effective adjunctive biomarker. Since, most studies were on neonatal population, evidence may not be generalized to older pediatric populations. Further large-scale prospective studies are needed to establish standardized cut-off values and validate its clinical utility.Registration No: PROSPERO (No. CRD420261338676).

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