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valproate semisodium (Depakote ER / divalproex ER)

✓ Approved

AbbVie, Inc. · SCN1A · Small Molecule

What is valproate semisodium?

valproate semisodium is a small molecule developed by AbbVie, Inc.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesDepakote ER, divalproex ER
CompanyAbbVie, Inc.
Drug ClassSmall Molecule
Molecular TargetSCN1A, SCN2A, SCN3A
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, AbbVie, Inc.

Mechanism of Action

Molecular Targets

valproate semisodium acts on 3 molecular targets:

SCN1Asodium voltage-gated channel alpha subunit 1 (DEE6B, FEB3)
SCN2Asodium voltage-gated channel alpha subunit 2 (Na(v)1.2, BFNIS)
SCN3Asodium voltage-gated channel alpha subunit 3 (Nav1.3, NAC3)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

valproate semisodium is developed for 3 unique indications across 3 therapeutic areas.

Therapeutic AreaConditionPhase
Nervous system disordersGeneralised tonic-clonic seizure✓ Approved
Psychiatric disordersBipolar disorder✓ Approved
Surgical and medical proceduresMigraine prophylaxis✓ Approved

Related Research Articles

PubMedSmart molecules : open access2026-07-25

A lysosomal escape-enabled endoplasmic reticulum-targeting BODIPY photothermal agent for enhanced tumor ablation.

Shi Shaoyang S, Cao Yanbing Y, Zuo Jiexuan J, Li Qiushi Q et al.

Photothermal therapy (PTT) has emerged as a promising minimally invasive strategy for tumor treatment due to its high selectivity, minimal drug resistance, and precise controllability. However, the efficacy of PTT is often limited by the inability of photothermal agents (PTAs) to effectively target subcellular organelles after cellular uptake. In this study, we designed and synthesized an endoplasmic reticulum (ER)-targeting BODIPY-based photothermal agent (ER-BDP) by functionalizing a trifluoromethyl-substituted BODIPY scaffold with a p-toluenesulfonyl group. The resulting ER-BDP nanoparticles (ER-BDP NPs), co-assembled with DSPE-PEG2000-Biotin, exhibit excellent near-infrared absorption (λmax = 780 nm), high photothermal conversion efficiency (80.3%), and efficient tumor targeting via the enhanced permeability and retention (EPR) effect. Importantly, ER-BDP NPs demonstrate the ability to escape from lysosomes and specifically accumulate in the ER, where localized photothermal heating induces severe ER stress and apoptosis. In vitro and in vivo studies confirm that ER-BDP NPs effectively ablate tumor cells under mild laser irradiation (760 nm, 500 mW cm-2) while showing negligible systemic toxicity. This work provides a rational design strategy for organelle-targeting photothermal agents and highlights their potential for enhanced tumor therapy.

PMID 42500718
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PubMedOncology letters2026-07-25

PRR11 expression in early ER+/HER2-low breast cancer: Association with estrogen receptor positivity and exploratory analysis of prognostic significance.

Turkel Alper A, Dogan Mutlu M, Irkkan Sultan Cigdem SC, Erdem Haktan Bagis HB et al.

The present study aimed to investigate proline-rich protein 11 (PRR11) expression and to exploratorily assess its prognostic relevance in early estrogen receptor (ER)+/HER2-low breast cancer. Data of 124 patients with early ER+/HER2-low breast cancer were evaluated retrospectively. PRR11 expression was analyzed in tumor tissues and reported as the median fold change relative to the cohort median. PRR11 expression was comparatively analyzed in subgroups according to ER percentages in 10% intervals and HER2-low status: CerbB2 immunohistochemistry (IHC) +1 (n=66) and +2 (n=58). PRR11 expression analysis was also performed in the residual tumors of patients who received neoadjuvant chemotherapy (NAC; n=14) and patients without pathological complete response (pCR; n=11). The median PRR11 expression fold change was 0.31 in the ER (1-10%) subgroup, 0.50 in the ER (20-30%) subgroup, 1.19 in the ER (40-50%) subgroup, 1.23 in the ER (70-80%) subgroup, 1.41 in the ER (80-90%) subgroup and 1.55 in the ER (>90%) subgroup. The median fold change in PRR11 expression was 1.717 in the CerbB2 IHC 1+ subgroup and 0.999 in the CerbB2 IHC 2+ subgroup. PRR11 expression was decreased in 4 patients (36%) and increased in 7 patients (64%) after NAC. Kaplan-Meier survival analysis stratified by PRR11 expression did not indicate a statistically significant difference in 5-year disease-free survival (DFS) or overall survival between the high- and low-PRR11 expression groups. Receiver operating characteristic analysis of DFS yielded an area under the curve of 0.409 (optimal cut-off, 0.18; sensitivity, 100%; specificity, 15.3%), indicating no meaningful discriminatory value. There was a positive association between PRR11 expression and the ER positivity rate. Higher PRR11 levels in residual tumors of non-pCR patients represented a preliminary, hypothesis-generating observation regarding the potential predictive value of PRR11 in patients receiving NAC. Randomized clinical trials are needed in this area.

PMID 42500608
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PubMedComprehensive psychoneuroendocrinology2026-07-25

Distinct intrinsic neural connectivity of an emotion regulation network across the menopausal transition.

Weinmar Franziska F, Kimmig Ann-Christin S AS, Amaoui Sofia S, Gervais Laura L et al.

Menopause is a major psychoneuroendocrine transition which can impact emotional functioning and mental health. Although emotion regulation (ER) is fundamental for mental health, intrinsic neural connectivity supporting ER across the menopausal transition remains unexplored. Addressing this gap, this study provides the first examination of intrinsic effective connectivity within an ER-related network across menopausal stages. Resting-state fMRI data were acquired from 76 healthy premenopausal (n = 32), perimenopausal (n = 19), and postmenopausal (n = 25) women. Effective connectivity within a predefined ER network was examined using spectral dynamic causal modeling. Further, we assessed how intrinsic connectivity predicts self-reported ER ability within each group. While self-reported ER ability did not differ across groups, resting-state effective connectivity within the ER network varied in a stage-specific manner, with the most heterogeneous effects observed between pre- and perimenopause, suggesting a non-monotonic pattern of between-group differences. Perimenopause was characterized by distinct frontal interaction patterns, reflecting a stage-specific redistribution of network organization rather than a gradual intermediate between pre- and postmenopausal connectivity profiles. Differences regarding postmenopause were restricted to greater weighting of temporo-parietal network components. Connectivity-ER ability associations revealed stage-specific predictive profiles, with distributed fronto-temporal connectivity predicting ER ability in premenopause, frontal-restricted connectivity in perimenopause, and a single frontal connection with reversed predictive direction in postmenopause. Our findings demonstrate that comparable levels of trait-based ER ability are associated with divergent intrinsic network configurations rather than a uniform architecture. Identifying perimenopause as distinct stage of intrinsic network organization advances hormone-sensitive models of intrinsic connectivity and provides a framework for understanding how baseline network organization may adapt during psychoneuroendocrine transitions in women.

PMID 42499590
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PubMedJournal of the National Cancer Institute2026-07-25

Clarifying risk-factor associations with quantitative breast tumor features: a pooled analysis of 24 studies.

Adams Daniel D, Hurson Amber N AN, Ahearn Thomas U TU, Andrulis Irene L IL et al.

Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

PMID 42498670
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PubMedToxicology in vitro : an international journal published in association with BIBRA2026-07-25

Transcriptomic analysis identifies key genes and mechanisms involved in dibutyl phthalate-induced alteration in hepatic stellate cells.

Ko Eun-A EA, Jung Sung-Cherl SC, Lee Hyang-Ae HA, Kang Dawon D et al.

Dibutyl phthalate (DBP) is a widely used phthalate plasticizer and endocrine disruptor implicated in hepatic injury and fibrosis. However, its direct impact on hepatic stellate cells (HSCs) remains insufficiently characterized. In this study, we examined DBP-induced transcriptomic alterations and functional pathways in HSCs. RNA sequencing of 42,844 genes identified 981 significantly differentially expressed genes (FDR < 0.05), followed by validation using qPCR and Western blot analysis. Gene Ontology (GO) and KEGG enrichment analyses revealed strong activation of endoplasmic reticulum (ER) stress, autophagy, apoptosis, and calcium signaling pathways. Heatmap clustering further highlighted upregulation of ER stress- and autophagy-related genes, consistent with increased autophagic degradation and apoptotic signaling. Notably, genes regulating Ca2+ homeostasis were markedly dysregulated, showing enhanced expression of Ca2+-permeable channels and suppression of K+ channels, indicating a shift in intracellular ion dynamics. Collectively, DBP exposure severely disrupts HSC transcriptomic equilibrium through concerted activation of ER stress, autophagy, apoptosis, and calcium signaling. These findings identify ER stress-Ca2+ signaling crosstalk as a mechanistic hub linking DBP exposure to fibrogenic liver injury and establish a transcriptome-resolved framework for elucidating phthalate-induced hepatotoxicity and advancing risk assessment strategies.

PMID 42497967
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PubMedJournal of environmental sciences (China)2026-07-25

Endoplasmic reticulum stress-mediated glycophagy drives macrophage M1 polarization in silica nanoparticles-induced pulmonary fibrosis.

Bao Lei L, Geng Zihan Z, Niu Linpeng L, Shi Lili L et al.

Inhalation of silica nanoparticles (SiNPs) triggers progressive pulmonary fibrosis, a pathological process closely associated with macrophage polarization. However, its underlying molecular mechanisms have not been fully elucidated. To elucidate the pathogenic mechanisms, we developed both an mice model of SiNPs-induced pulmonary fibrosis coupled with an indirect co-culture model of RAW264.7 and NIH/3T3 cells. Our findings demonstrated that SiNPs not only promoted macrophage M1 polarization but also led to pulmonary fibrosis. In the indirect co-culture model, M1-polarized RAW264.7 cells induced by SiNPs significantly upregulated collagen I and α-SMA expression in NIH/3T3 cells through enhanced secretion of cytokines IL-6 and TNF-α. Mechanistic investigations uncovered that SiNPs markedly augmented endoplasmic reticulum (ER) stress in RAW264.7 cells, as evidenced by activation of the protein kinase R-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP)/HMG-CoA reductase degradation protein 1 (HRD1) axis. Bioinformatics mining molecular docking and Co-immunoprecipitation (Co-IP) assays demonstrated that HRD1 directly binds STBD1. Pharmacological inhibition of ER stress significantly attenuated M1 polarization in RAW264.7 cells, and subsequent fibrotic markers expression in NIH/3T3 cells via suppression of STBD1-mediated glycophagy activation. Genetic inhibition of glycophagy through STBD1 knockdown effectively reversed both ER stress-driven M1 polarization in RAW264.7 cells and fibrotic markers in NIH/3T3 cells. These findings collectively establish a novel mechanistic paradigm wherein ER stress-mediated glycophagy plays a pivotal role in driving macrophage M1 polarization during SiNPs-induced pulmonary fibrosis.

PMID 42498407
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