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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

PubMedCatheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions2026-10-15

Impaired Flow and Physiology in Coronaries With Anomalous Origin From the Opposite Sinus of Valsalva.

Lo Rito Mauro M, Squillace Mattia M, Agnifili Mauro Luca ML, Rosato Antonio A et al.

Anomalous Aortic Origin of a Coronary Artery (AAOCA) high-risk anatomical features (intramural segment, acute take-off angle, slit-like ostium) cause coronary stenosis leading to myocardial infarction. How these features alter coronary physiology remains unclear. We aimed to evaluate their impact on coronary blood supply using continuous thermodilution. We prospectively enrolled 51 AAOCA patients undergoing continuous thermodilution. Subjects were classified into an ischemic risk (IR) group (intramural segment, acute angle, oval or slit ostium) or non-ischemic risk (no-IR) group. Non-anomalous coronary arteries served as controls. We measured absolute coronary blood flow (CBF) and microvascular resistance. Subjects (median age 48.4 years) presented mostly with angina, syncope, and arrhythmia. Final analysis included 48 AAOCA cases (31 IR, 17 no-IR) and 45 controls. The IR group had a median IM length of 9 mm, take-off angle of 31.9°, and a slit-like or oval ostium. The no-IR group had a median angle of 51.5° and an oval or round ostium. At rest, absolute CBF and microvascular resistance showed no significant differences among groups. However, during hyperemia, the IR group had significantly reduced CBF compared to controls (179 vs. 290 mL/min, p = 0.015). The IR group demonstrated higher microvascular resistance at rest (1473 vs. 1150, p = 0.024) and during hyperemia (433 vs. 305, p = 0.012), indicating persistently increased coronary vascular tone. High-risk anatomical features of AAOCA are associated with altered coronary physiology. An intramural segment, acute take-off angle, and slit-like or oval ostium are linked to reduced hyperemic coronary blood flow due to increased microvascular resistance.

PMID 42876388
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PubMedFrontiers in endocrinology2026-10-15

Age-specific association between remnant cholesterol and insulin resistance in women with polyendocrine metabolic ovarian syndrome.

Yu Chiyuan C, Sun Zhonghua Z, Wu Qinyao Q, Zhou Zhiyi Z et al.

Insulin resistance (IR) is a major metabolic feature in women with polyendocrine metabolic ovarian syndrome (PMOS). Remnant cholesterol (RC), which reflects the cholesterol burden of triglyceride-rich remnant lipoproteins (TRLs), may capture lipid disturbances related to insulin-resistant dyslipidemia. Whether RC is linked to IR in women with PMOS remains unclear. This study enrolled 617 women with PMOS. Participants were grouped according to natural-log-transformed remnant cholesterol (lnRC) quartiles. Adjusted odds ratios (ORs) for IR were estimated using multivariable logistic regression models, and restricted cubic splines (RCS) were fitted to characterize the potential dose-response patterns. Multiplicative and additive interaction analyses were performed to evaluate the interaction between age and lnRC. Discrimination of IR by lnRC was assessed using receiver operating characteristic (ROC) curve, and age-specific estimates were compared using DeLong's test. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to assess whether lnRC added information beyond the base model. Higher lnRC levels were significantly associated with increased odds of IR (Q4 vs. Q1: odds ratio [OR] = 3.11, 95% confidence interval [CI]: 1.57-6.14, P = 0.001). This relationship was stronger in women aged < 30 years than in those aged ≥ 30 years (OR: 2.01 vs. 1.13, P for interaction = 0.046). A multiplicative interaction between age and lnRC was also observed for IR (OR = 0.438, 95% CI: 0.197-0.977, P = 0.044). Exploratory age-stratified ROC analysis showed that the area under the curve (AUC) of lnRC for IR discrimination was higher among women aged <30 years than among those aged ≥30 years (0.654 vs. 0.523, DeLong P = 0.024). Adding lnRC to the base model improved risk reclassification and discrimination (NRI = 0.381, 95% CI: 0.165-0.597, P = 0.001; IDI = 0.025, 95% CI: 0.007-0.0439, P = 0.005). This study indicates that the lnRC-IR association was stronger in women aged <30 years, and a multiplicative interaction between lnRC and age group was observed. These findings suggest that RC may provide complementary information for metabolic assessment in younger women with PMOS and support its further evaluation as a readily calculable lipid marker.

PMID 42876462
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PubMedMolecular medicine (Cambridge, Mass.)2026-10-15

Elucidating the mechanism underlying incomplete immune recovery in people living with HIV through CD4⁺ and CD8⁺ T cell multi-omics.

Flores-Piñas Marina M, Chafino Silvia S, Viladés Consuelo C, Domingo Pere P et al.

A subset of people living with HIV (PLHIV), known as immunological non-responders (INR), fails to achieve adequate CD4⁺ T cell recovery despite viral suppression with antiretroviral therapy (ART). These individuals face an increased risk of adverse clinical outcomes. This study aims to explore the intracellular mechanisms and molecular signatures underlying this incomplete immune recovery using a multi-omics approach. The study analysed CD4⁺ and CD8⁺ T cells from 100 ART-naïve PLHIV. Participants were classified into controls (baseline CD4⁺ > 200 cells/µL, n = 49) and cases (baseline CD4⁺ ≤ 200 cells/µL, n = 51). Cases were further categorised after 48 weeks of ART as immunological responders (IR, n = 34) or INR (n = 16) based on a recovery cut-off of 250 cells/µL. The research employed integrative proteomic and metabolomic analyses, adjusted for sex, complemented by miRNA and qRT-PCR validation in a subset of samples to identify differential molecular signatures. In CD4⁺ T cells, a baseline signature of 381 proteins and 45 metabolites significantly differentiated controls from cases; notably, 34 proteins and 16 metabolites specifically discriminated future IR from INR before starting treatment. CD8⁺ T cells showed a more limited signature with minimal stratification between IR and INR. Integrative analysis revealed coordinated dysregulation in CD4⁺ T cells of INR, characterised by altered glycolytic flux, metabolic exhaustion, and oxidative stress. Exploratory analyses via miRNA and qRT-PCR confirmed these findings and suggested post-transcriptional mechanisms contribute to the impairment. Incomplete immune recovery in PLHIV is primarily driven by pre-existing metabolic dysfunction and oxidative stress within CD4⁺ T cells, rather than CD8⁺ T cells. These findings identify specific molecular signatures present before ART initiation, highlighting early potential therapeutic targets and strategies to enhance immune reconstitution in this vulnerable population.

PMID 42875740
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PubMedThe Journal of clinical endocrinology and metabolism2026-10-15

Waist circumference outperforms cardiometabolic indices for identifying hypogonadism in Klinefelter Syndrome.

Graziani Andrea A, Nardin Matteo M, Grande Giuseppe G, Pollis Riccardo Maria RM et al.

Klinefelter syndrome (KS) is characterized by primary hypogonadism and increased cardiometabolic risk. The utility of cardiometabolic indices remains unclear. To evaluate whether anthropometric and cardiometabolic indices provide incremental value beyond age for identifying hypogonadism in men with KS. Retrospective cross-sectional cohort study at a tertiary referral center. 580 patients with KS were evaluated. Analyses assessing biochemical hypogonadism were restricted to untreated patients with available calculated free testosterone (cFT) concentrations (n = 328). Biochemical androgen deficiency was defined as cFT <0.220 nmol/L. Discriminative performance and incremental value of WC, LAP, TyG, and HOMA-IR were assessed using logistic regression, ROC analyses, reclassification analyses, decision curve analysis (DCA), and bootstrap validation. Among untreated patients, 64.9% had biochemical hypogonadism. WC showed the highest discriminative ability (AUC 0.747) and slightly greater discrimination than cardiometabolic indices including LAP (AUC 0.704), HOMA-IR (AUC 0.681), and TyG index (AUC 0.612). In multivariable analyses adjusted for age, WC remained independently associated with hypogonadism (OR 1.05 per cm; p < 0.001). Age alone yielded an AUC of 0.744, which increased to 0.796 after addition of WC (p = 0.007), whereas addition of LAP resulted in only modest improvement (AUC 0.758). Addition of WC improved reclassification beyond age. DCA demonstrated consistent gains in clinical net benefit with inclusion of WC, whereas composite cardiometabolic indices provided limited additional utility. In KS, WC provides incremental value beyond age for identifying hypogonadism, whereas composite cardiometabolic indices offer limited additional discriminatory value. These findings suggest that simple anthropometric assessment may support endocrine-metabolic stratification in KS.

PMID 42875728
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PubMedChemistry (Weinheim an der Bergstrasse, Germany)2026-10-15

In Situ Infrared Spectroscopy Analysis of Dehydrogenation of Perhydro-N-ethylcarbazole.

Jiang Yufei Y, Li Tingzhou T, Lu Guofu G, Zhou Jin J et al.

The dehydrogenation mechanism of perhydro-N-ethylcarbazole (12H-NEC), a promising liquid organic hydrogen carrier (LOHC), on Pd/Al2O3 catalyst was studied by in situ FT-IR analysis. Spectra were collected in transmission mode using a 12H-NEC/catalyst/KBr mixture pellet to overcome the difficulty of introducing low-volatility 12H-NEC. A peak-deconvolution, assignment, and normalization protocol was developed to interpret the complex C─H stretching region from 3100 to 2750 cm-1. The results indicate that dehydrogenation begins at the five-membered ring and that species spectroscopically consistent with 8H-NEC accumulate at approximately 100°C. A transient spectral state observed before this accumulation is consistent with an earlier partially dehydrogenated intermediate, for which 10H-NEC is one possible structural assignment. This work provides experimental insight into the dehydrogenation mechanism of 12H-NEC under mild conditions and may guide further efforts to improve the hydrogen-storage performance of 12H-NEC-based LOHC systems.

PMID 42876399
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PubMedSmall (Weinheim an der Bergstrasse, Germany)2026-10-15

Accessing Both Electrochemical SEIRA and SERS With Highly Sensitive Metamaterials for Enhanced Molecular Identification.

Spiesshofer Nicolas N, Jones Tabitha T, Sibug-Torres Sarah May SM, Sztranyovszky Zoltan Z et al.

Surface-enhanced IR absorption (SEIRA) and surface-enhanced Raman spectroscopy (SERS) are complementary techniques that allow for highly sensitive chemical fingerprinting. Non-invasive optical sensing would be significantly improved by a robust implementation of a reusable substrate that combines these techniques. Here, we present an electrochemically cleanable metamaterial that enables flow-compatible real-time SEIRA and SERS. This metamaterial facilitates the study of surface-adsorbed species and diffusion layers, elicits spectral shifts from changes in nanogap refractive index of 1400 nm/RIU, and delivers sensitive analyte detection. Combining SERS and SEIRA clarifies molecular (electro)chemical transformations and tracks changes in selection rules and symmetry breaking at the analyte-electrode interface. This development in enhanced multimodal spectro-electrochemistry is suited for multiple domains, including understanding charge transport mechanisms and interfacial dynamics at electrodes, and is capable of real-time flow monitoring for a wide range of molecular processes.

PMID 42876114
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