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isosorbide dinitrate + hydralazine (hydralazine + ISDN / BiDil / ISDN + hydralazine)

✓ Approved

Arbor Pharmaceuticals, LLC · CACNA1C · Small Molecule

What is isosorbide dinitrate + hydralazine?

isosorbide dinitrate + hydralazine is a small molecule developed by Arbor Pharmaceuticals, LLC. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand Nameshydralazine + ISDN, BiDil, ISDN + hydralazine
CompanyArbor Pharmaceuticals, LLC
Drug ClassSmall Molecule
Molecular TargetCACNA1C
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Arbor Pharmaceuticals, LLC

Mechanism of Action

Molecular Targets

isosorbide dinitrate + hydralazine acts on 1 molecular target:

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

isosorbide dinitrate + hydralazine is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Cardiac disordersCardiac failure✓ Approved

Related Research Articles

PubMedCancer medicine2026-09-19

Persistent Racial Disparities in Breast Cancer Incidence by Stage and Subtype in a High-Burden State.

Barsha Rifath Ara Alam RAA, Miller-Kleinhenz Jasmine J

Breast cancer incidence varies by race, stage at diagnosis, and molecular subtype. However, these patterns are often obscured in overall estimates, particularly in high-burden settings. This study examined incidence trends overall and by race, stage at diagnosis, and molecular subtype among women in Mississippi. We used population-based data from the Mississippi Cancer Registry, including Black and White women aged ≥ 18 years diagnosed with primary breast cancer from 2010 to 2019. Age-adjusted incidence rates (IRs) per 100,000 population were standardized to the 2000 United States standard population. Trends were assessed using Joinpoint regression estimating average annual percent changes (AAPCs) and annual percent changes (APCs). Multivariable Poisson regression estimated incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Among 21,130 women (64.4% White; 35.6% Black), the overall age-adjusted IR was 166.0 per 100,000 with no significant change over time (AAPC = 0.48%; 95% CI: -0.27 to 1.24). Black women had higher incidence than White women (178.0 vs. 159.1). Among White women, incidence increased modestly (AAPC = 0.60%; 95% CI: 0.06-1.13). Trends among Black women were not significant overall (AAPC = 0.36%; 95% CI: -0.25 to 1.04) but increased from 2014 to 2019 (APC = 1.95%; 95% CI: 0.77-4.26) after an initial decline. Localized-stage incidence increased in both groups, while Black women had higher regional- and distant-stage incidence. In adjusted models, Black women had higher incidence of HER2-overexpressing (IRR = 1.55; 95% CI: 1.15-2.10) and triple-negative cancer (IRR = 2.35; 95% CI: 1.74-3.17) than White women. Overall incidence remained stable, but substantial heterogeneity across subgroups underscores the need for stratified surveillance and equity-focused cancer control strategies in high-burden settings.

PMID 42760641
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PubMedFrontiers in endocrinology2026-09-19

The association between the triglyceride-glucose index and diabetic peripheral neuropathy: a systematic review and meta-analysis.

Gu Xin X, Wei Maoying M, Wu Chan C, Li Aijing A et al.

Diabetic peripheral neuropathy (DPN) is a prevalent and severe microvascular complication of type 2 diabetes mellitus (T2DM). Early risk screening and warning are critical for slowing disease progression. The triglyceride-glucose (TyG) index, a simple and efficient surrogate marker for assessing insulin resistance (IR), has been proven to be closely associated with various diabetic complications. However, existing studies on the association between the TyG index and the risk of DPN have yielded inconsistent findings, and relevant evidence still lacks systematic synthesis. A systematic review and meta-analysis were conducted. We systematically searched databases including PubMed, Embase, Web of Science, CNKI, Wanfang, and CQVIP to enroll observational studies exploring the association between the TyG index and the risk of DPN in patients with T2DM. Two investigators independently performed literature screening, data extraction, and quality assessment. The random-effects and fixed-effects models were applied to pool effect sizes, and subgroup analyses were carried out to explore potential sources of heterogeneity. A total of 14 studies involving 32,281 participants were included. The results showed that a higher TyG index was associated with an increased risk of DPN, with a pooled odds ratio (OR) of 2.614 (95% CI: 1.788-3.821, P < 0.0001) and a pooled hazard ratio (HR) of 1.248 (95% CI: 1.003-1.553, P = 0.0471). This positive correlation remained consistent across most subgroups stratified by age, sample size, BMI, and adjustment for confounding factors. However, the association did not reach statistical significance in the non-China subgroup. Elevated TyG levels are associated with an increased risk of DPN in patients with T2DM. However, the causal relationship requires further validation. These findings may serve as a reference for clinical screening of DPN risk. https://www.crd.york.ac.uk/prospero, identifier CRD420261373476.

PMID 42760994
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PubMedFrontiers in nutrition2026-09-19

Nobiletin ameliorates diabetic nephropathy by modulating TP53-associated PANoptosis: an experimental study.

Zhang Biwei B, Liu Yi Y, Ma Leilei L, Zhao Yingjie Y et al.

Nobiletin (NOB), a naturally occurring polymethoxyflavone enriched in Citri Reticulatae Pericarpium-the dried peel of mature citrus fruit-has attracted increasing attention because of its multi-target pharmacological activities. This study explored the protective effects of NOB on diabetic nephropathy (DN), with a focus on TP53-associated PANoptosis and TFEB-related lysosomal and energy metabolic changes. Forty male db/db mice were randomly assigned to the model, metformin, low-dose NOB (30 mg/kg/day), and high-dose NOB (60 mg/kg/day) groups, with 10 mice per group. Ten age-matched male db/m mice served as non-diabetic controls. Treatments were administered by gavage for 8 weeks. Metabolic parameters, lipid profiles, inflammatory cytokines, renal function, histopathology, untargeted metabolomics, energy metabolites, network pharmacology, surface plasmon resonance (SPR), immunofluorescence, qPCR, and Western blot analyses were performed. Supplementary in vitro validation was performed in high-glucose-treated HK2 renal tubular epithelial cells with TP53 knockdown or overexpression. NOB treatment reduced FBG, OGTT-AUC, INS, HOMA-IR, GSP, TC, TG, and LDL-C while increasing HDL-C. High-dose NOB improved renal function, reduced IL-1β and IL-6, and alleviated histological damage. Untargeted metabolomics suggested that NOB partially restored pathway-level changes related to oxidative phosphorylation, lysosomal function, fatty acid metabolism, and energy metabolism. Network pharmacology identified TP53 as a central candidate target, and SPR analysis suggested binding between NOB and TP53 protein. NOB treatment reduced TP53 signal, promoted TFEB nuclear localization, and suppressed pyroptosis-, apoptosis-, and necroptosis-related markers in diabetic kidneys. Representative HK2 Western blot experiments showed expression patterns consistent with attenuation of high-glucose-induced PANoptosis-related protein activation after TP53 knockdown and partial counteraction of the NOB-associated regulatory pattern after TP53 overexpression. NOB ameliorated DN-related metabolic disturbance, inflammation, renal dysfunction, histological injury, and fibrosis. These protective effects were associated with reduced TP53 activation, restoration of TFEB-related lysosomal and energy metabolic status, and suppression of PANoptosis-related pathways. Supplementary HK2 cell experiments provided supportive, representative evidence for the involvement of TP53 in high-glucose-induced PANoptosis-related protein activation and in the regulatory effect of NOB. These findings suggest that NOB may be a promising natural compound for DN intervention.

PMID 42761023
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PubMedACS omega2026-09-18

Systematic Understanding of Freely Optimized Excited-State Evolution in Ir(III) Photocatalysts.

Fortna Cristabella R CR, Fredin Lisa A LA

Polypyridyl Ir-(III) complexes have dominated the field of transition metal photocatalysis due to their diverse tunability, photostability, and microsecond excited state lifetimes. Numerous studies have addressed structure-property and structure-activity relationships of Ir-(ppy)3 and [Ir-(ppy)2(bpy)]+ parent complexes, using density functional theory to explain experimental excited-state reactivity of the photoactive triplet states, but few works characterize the relationship of the competing charge-transfer and metal-centered triplet states and fewer still explore photoactive archetypes beyond the Ir-(ppy)3 and Ir-(ppy)2(bpy) classes. This work employs density functional theory to characterize and quantify the excited state surfaces of six Ir-(III) parent complexes and their isomers to gain a systematic understanding of how coordination at the metal center impacts photoactivity. The photophysical impact of (1) increasing the number of Ir-N contacts with bpy-type ligands, (2) altering through-metal C-Ir-N contact orientation and (3) increasing ligand rigidity and conjugation with fused aromatic rings is explored by plotting projected potential energy surfaces along quantitative energetic and structural axes. This investigation provides a theoretical understanding to support Ir-(III) fame and versatility as a photocatalyst, providing quantum mechanical characterization of design principles that augment excited state lifetimes.

PMID 42757151
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PubMedCancer cell international2026-09-18

Enhanced survival through repeated photodynamic therapy and almost complete tumor regression by prior radiation therapy in an orthotopic rat bladder cancer model.

Berndt-Paetz Mandy M, Nürnberger Sandra S, Gonsior Susann S, Pączek-Hippe Ewelina E et al.

The development of new organ-preserving treatment alternatives is still an important issue in bladder cancer (BCa) research. A combination of minimally-invasive photodynamic therapy (PDT) with ionizing radiation (IR) could be beneficial for bladder tumor regression. Here, we tested the hypothesis that PDT with the near-infrared photosensitizer tetrahydroporphyrin-tetratosylate (THPTS) could treat bladder tumors safely and effectively in an orthotopic rat model. Response additivity analysis of cytotoxicity was investigated in cultured tumor cells (AY-27) and spheroids consisting of AY-27 and bladder fibroblasts of F344 Fischer rats. For in vivo evaluation, tumors were induced in female Fischer rats by intravesical instillation of AY-27 cells. Triple-time treatments were performed, with ten rats each in four treatment groups: untreated controls (UTC), PDT, IR, PDT with prior IR (IR + PDT). Animals were euthanized when reaching the termination criteria, and bladders were evaluated by macroscopy, histology and CD45 immunohistology. Synergism of combined treatment was demonstrated for all tested THPTS concentrations in AY-27/fibroblast spheroids but not in 2D cultured AY-27 cells. Tumor cell inoculation resulted in massive growth of solid bladder tumors (pT3a/b) in UTC. Triple-time treatment led to doubling of survival in the PDT group (mOS: 70 d) compared to UTC group (mOS: 36.5 d). IR monotherapy and IR + PDT resulted in complete survival without reaching the termination criteria. Histology revealed advantage of combination therapy vs. IR monotherapy by demonstrating treatment responses in all tumors of the IR + PDT group. This is the first in vivo study reporting doubling of survival time after PDT with a new near-infrared photosensitizer, and nearly complete tumor remission by neoadjuvant IR. This multimodal approach possibly allows minmally-invasive, organ-preserving BCa treatment.

PMID 42754885
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PubMedACS applied materials & interfaces2026-09-18

A pH-Responsive Ceria-Supported Iridium Clusterzyme for Combined Antibacterial and Anti-inflammatory Therapies in Diabetic Wound Healing.

Zhu Huang H, Li Waner W, Li Qingjie Q, Li Jianlan J et al.

The treatment of diabetic wounds is hindered by multiple factors, including Staphylococcus aureus (S. aureus) biofilms (the predominant pathogen in diabetic wound infections), dysregulated immune responses, and insufficient angiogenesis. The complex interactions among these local pathological factors have been insufficiently addressed in the development of existing therapeutic approaches. This study reports a hybrid biocatalytic platform consisting of abundant iridium (Ir) clusters supported on ceria (Ir-CeO2). This architectural configuration enables pH-responsive reactive oxygen species (ROS) catalysis, allowing the biocatalyst to exert concurrent antimicrobial and anti-inflammatory effects, which collectively promote healing of diabetic wounds. Ir-CeO2 displays dual pH-dependent ROS modulation: ROS generation under acidic conditions and ROS scavenging under neutral pH. In S. aureus-infected environments, the biocatalyst exerts potent antibacterial effects via catalytic ROS production. Following pathogen clearance, Ir-CeO2 continues to play a bifunctional role by alleviating oxidative stress in inflamed wounds, promoting the polarization of macrophages toward the M2 phenotype-a critical event for accelerating wound healing. Collectively, these results highlight the multifaceted therapeutic efficacy of Ir-CeO2, which seamlessly integrates potent antibacterial activity against S. aureus infections with anti-inflammatory and pro-angiogenic functions. This synergistic profile establishes Ir-CeO2 as a highly promising agent for the holistic management of complicated diabetic ulcers, thereby addressing key shortcomings of existing treatment modalities.

PMID 42758942
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