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diltiazem (Cardizem QD / Dilzem XL / Angiact)

✓ Approved

Mitsubishi Tanabe Pharma Corporation · CACNA1C · 小分子

什么是 diltiazem？

diltiazem 是一种小分子，由Mitsubishi Tanabe Pharma Corporation研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Cardizem QD, Dilzem XL, Angiact
公司Mitsubishi Tanabe Pharma Corporation
药物类别小分子
分子靶点CACNA1C
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Mitsubishi Tanabe Pharma Corporation

作用机制

分子靶点

diltiazem 作用于 1 个分子靶点：

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

diltiazem 针对 2 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Cardiac disordersAngina pectoris✓ Approved
Vascular disordersHypertension✓ Approved

相关研究文献

PubMedJournal of attention disorders2026-07-27

Relative Bioavailability of Once-Daily Clonidine XR Oral Suspension Versus Twice-Daily XR Tablets in Healthy Volunteers.

Jain Rakesh R, Rafla Eman E, Grieco Joseph C JC, Witkovic Matthew M et al.

To assess the bioequivalence of once-daily clonidine extended-release (XR) oral suspension (OS) to twice-daily clonidine XR tablets (TABs), which are approved for attention-deficit/hyperactivity disorder (ADHD). Study 1 (n = 20) evaluated an equivalent daily dose of clonidine XR OS versus TABs and clonidine XR OS under fed versus fasted conditions. Outcomes included the maximum plasma concentration (Cmax), the area under the analyte versus time curve (AUC) from 0 to the last analyte concentration (AUCt) and to infinity (AUCinf), and the half-life (Thalf). Study 2 (n = 19) evaluated AUC, Cmax, and the minimum concentration (Cmin) at steady state (SS). The ratios of geometric means and corresponding 90% CIs of pharmacokinetic parameters for each treatment were compared to the US Food and Drug Administration definition of bioequivalence (80%-125%). In Study 1 (mean [SD] age, 42 [11] years; 30% female; 10% Asian, 25% Black or African American, 5% Multiracial, 60% White; 40% Hispanic or Latino), the ratios (90% CIs) of clonidine XR OS to TABs were within the bioequivalence range accepted by the FDA for Cmax (95.6 [89.8, 101.8]), AUCt (97.2 [91.6, 103.1]) and AUCinf (96.1 [89.4, 103.4]); similar results were observed for clonidine XR OS under fed versus fasting conditions. The median (range) Thalf was 12.8 (8-24) hours. In study 2 (mean [SD] age, 43 [11] years; 42% female; 47% Asian, 26% Black or African American, 0% Multiracial, 26% White; 0% Hispanic or Latino), AUCt,ss and Cmax,ss were both within the acceptable range (97.7 [93.4, 102.1] and 107.9 [103.8, 112.2], respectively). The Cmin,ss for clonidine XR OS was ~26% lower than clonidine XR TABs (74.0 [69.3, 79.0]) but this difference was not considered clinically meaningful by the FDA. These results demonstrate that clonidine XR OS is bioequivalent to clonidine XR TABs and could fulfill a treatment gap as a liquid, once-daily, non-stimulant ADHD treatment option.

PMID 42503630
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PubMedDiabetes, obesity & metabolism2026-07-27

Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).

Rodbard Helena W HW, Irace Concetta C, Lobo Jevitha J, Makrilakis Konstantinos K et al.

Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0 mg as add-on to dose-reduced insulin glargine (Sema+IGlarreduced) versus dose-titrated IGlar (IGlartitrated) on glycated haemoglobin (HbA1c), body weight (BW), daily insulin dose, and participant satisfaction. SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index ≥ 25 kg/m2), and treatment with basal insulin ≤ 40 units/day were randomised 1:1 into Sema+IGlarreduced or IGlartitrated. The primary endpoint was change in HbA1c using a non-inferiority approach. Secondary endpoints assessed superiority of Sema+IGlarreduced versus IGlartitrated in reducing HbA1c, BW, daily insulin dose, and improving Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) scores. Overall, 573 participants were randomised. Sema+IGlarreduced achieved both non-inferiority and superiority versus IGlartitrated in HbA1c reduction (estimated treatment difference [ETD]: -0.74%; 95% confidence interval [CI95]: -0.90, -0.59) and superiority in BW change (ETD: -8.5 kg; CI95: -9.5, -7.4), relative daily insulin dose change (ETD: -121.9%; CI95: -143.1, -100.6), and DTSQc scores (ETD: 2.6; CI95: 1.6, 3.5) (p < 0.0001 for all endpoints). No new safety concerns were identified. Severe hypoglycaemia was reduced (rate ratio: 0.45; CI95: 0.23, 0.87; p = 0.02), while gastrointestinal events were higher for Sema+IGlarreduced (310 vs. 32 events). Once-weekly subcutaneous semaglutide 2.0 mg as add-on to dose-reduced IGlar achieved superior reductions in HbA1c, BW, and daily insulin dose in people with T2D and overweight, while reducing their risk for severe hypoglycaemia compared to dose-titrated IGlar alone.

PMID 42504064
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PubMedPhysiotherapy theory and practice2026-07-27

Determinants of daily activity value in a cross section of adults feeling pain.

Dannecker Erin A EA, Popejoy Lori L, Petroski Gregory F GF

Healthcare providers (HCPs) and patients value daily activities differently. So, HCPs routinely assess patients' preferences. To clarify the value of daily activities for people feeling pain, this study examined the influence of daily activity source (questionnaire or participant), daily activity performance, and daily activity-related difficulty and pain. The study also explored participants' perceptions of communicating daily activity-related difficulty and pain to HCPs. A cross-section of adults (N = 457; Mean age 39.17 years (SD = 16.33)) feeling pain reported the importance, performance, difficulty, and painfulness of daily activities. The sources of the daily activities were questionnaires and participants. The odds of higher daily activity importance were 10.85 times larger for the participant-generated daily activity than the questionnaire and 11.00 times larger for performed daily activities than the not performed. Higher daily activity importance was also associated with daily activity-related pain (odds ratio; OR:2.29) and age (OR:1.07), but not daily activity-related difficulty (OR:0.98). Participants' certainty about daily activity-related difficulty and pain was positively associated with daily activity source (ORs:1.35 and 1.75, respectively) and performance (ORs:1.76 and 1.80, respectively). In addition, the importance of HCPs knowing participants' daily activity-related difficulty and pain was associated with daily activity source (OR:1.94 and OR:1.63, respectively), performance (OR:1.56 and OR: 1.55, respectively), age (OR:1.06 and OR: 1.05, respectively), and daily activity-related difficulty (OR:1.49 and OR: 1.33, respectively) and pain (OR:2.92 and OR:2.92, respectively). These results clarify the daily activities that participants with pain value and want to discuss with their HCPs. This information facilitates the provision of patient-centered care. The results also suggest that the positive relationship between daily activity value and daily activity-related pain is stronger than daily activity-related difficulty. Expectancy value models of health behaviors would benefit from future research comparing the influence of daily activity-related difficulty on daily activity value and the expectation of performing daily activity.

PMID 42504101
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PubMedCancer medicine2026-07-27

A Phase I/II Study of Ibrutinib Plus Trastuzumab in HER2-Positive Metastatic Breast Cancer.

O'Shaughnessy Joyce J, Glidden Andrea A, Locke Tracy T, Scales Amy A et al.

Ibrutinib has demonstrated inhibition of ErbB/HER tyrosine kinases in preclinical models. This Phase I/II study investigated the safety, efficacy, and immunomodulatory effects of ibrutinib in combination with trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on ado-trastuzumab emtansine therapy. In Phase I, cohorts of three patients received ibrutinib 560 mg or 420 mg by mouth once daily combined with standard dosing of trastuzumab. Phase II enrolled additional patients to assess the primary endpoint of clinical benefit rate (CBR) at 420 mg ibrutinib plus trastuzumab. Flow cytometry and NanoString analyses were performed on peripheral blood mononuclear cells. Overall, 26 patients were enrolled. Patients received a median of three prior regimens containing a HER2-targeted therapy in any setting. The most common treatment-related adverse events were bruising, rash, fatigue, and thrombocytopenia. Four patients (15%) experienced cardiac adverse events, including decreased left ventricular ejection fraction in two patients. The CBR of ibrutinib plus trastuzumab was 19.2% (95% confidence interval: 6.6-39.4). Flow cytometry of T- and natural killer (NK)-cell and myeloid-cell panels showed that treatment statistically significantly decreased T helper 17 (TH17) and myeloid-derived suppressor cells (MDSC) with no decrease in T helper 2 (TH2) cells. Ibrutinib plus trastuzumab was well-tolerated but had limited anti-tumor activity in patients with heavily pretreated, HER2-positive MBC (NCT03379428). Trial Registration: Clinicaltrials.gov, NCT03379428.

PMID 42504645
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PubMedJAMA neurology2026-07-27

Efficacy and Safety of Gefurulimab in Generalized Myasthenia Gravis: The PREVAIL Phase 3 Randomized Clinical Trial.

Gwathmey Kelly G KG, Saccà Francesco F, Howard James F JF, Vu Tuan T et al.

Gefurulimab is a novel dual-binding nanobody that blocks complement component 5 activation. Complement activation is a key pathogenic mechanism in anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). To evaluate the efficacy and safety of gefurulimab in adults with AChR-Ab+ gMG. This randomized clinical trial, PREVAIL, was a phase 3, double-blind, placebo-controlled study conducted at 113 sites in 20 countries. Patients were screened and randomized from November 2022 to November 2024; the randomized controlled treatment period was 26 weeks. Participants were adults (aged ≥18 years) with AChR-Ab+ gMG, a Myasthenia Gravis Foundation of America classification II through IV, and a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 5 or higher. Gefurulimab or placebo via once-weekly subcutaneous self-injection. The primary end point was change from baseline in MG-ADL total score at week 26. The key secondary end point was change from baseline in Quantitative Myasthenia Gravis (QMG) total score at week 26. Safety was also assessed. Of 405 patients screened, 145 were excluded; 260 met eligibility criteria and were randomized (gefurulimab, n = 131; placebo, n = 129); 249 patients completed the 26-week randomized controlled treatment period. The mean (SD) age was 52.8 (15.73) years; 157 (60.4%) patients were female and 103 (39.6%) were male. All primary and secondary end points were met with statistical significance. Improvements occurred within 1 week for MG-ADL score and 4 weeks for QMG score and were sustained through week 26. Least-squares mean change from baseline at week 26 for MG-ADL and QMG total scores for gefurulimab vs placebo were -4.2 vs -2.6 (treatment difference, -1.6; 95% CI, -2.4 to -0.8; P < .001) and -4.5 vs -2.4 (treatment difference, -2.1; 95% CI, -3.1 to -1.1; P < .001), respectively. The incidence of adverse events (AEs) was similar between groups. Most common treatment-emergent AEs with gefurulimab were injection site reactions, headache, back pain, and nasopharyngitis. No meningococcal infections were reported. Gefurulimab demonstrated both early and sustained clinical benefit in AChR-Ab+ gMG and was well tolerated, supporting its potential as a convenient, once-weekly, self-administered treatment regimen. ClinicalTrials.gov Identifier: NCT05556096.

PMID 42507440
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PubMedACS chemical biology2026-07-27

Direct Small Molecule Modulation of LILRB4 (ILT3) Restores Antitumor Immunity In Vivo and in Patient-Derived Cells.

Abdel-Rahman Somaya A SA, Mariam Zamara Z, Deganutti Giuseppe G, Gabr Moustafa T MT

Small molecule targeting of suppressive myeloid immune checkpoints remains a major challenge in cancer immunotherapy, particularly for nonenzymatic receptors lacking conventional druggable active sites. Leukocyte immunoglobulin-like receptor B4 (LILRB4/ILT3) is an immunosuppressive myeloid checkpoint implicated in tumor immune evasion, T-cell dysfunction, and resistance to immunotherapy across both solid and hematologic malignancies. Here, we report the discovery and characterization of GL-4512, a direct small molecule modulator of LILRB4 identified through a Dianthus-based temperature-related intensity change (TRIC) screening platform. Orthogonal biophysical studies, including microscale thermophoresis, surface plasmon resonance, and cellular thermal shift assays, confirmed direct target engagement with nanomolar affinity. Extensive microsecond molecular dynamics simulations combined with site-directed mutagenesis identified a previously unrecognized ligandable pocket within the flexible extracellular domain of LILRB4. Functionally, GL-4512 disrupted the immunosuppressive LILRB4-SCG2 signaling axis and suppressed downstream SHP1/SHP2 and STAT3 signaling. In patient-derived colorectal cancer and acute myeloid leukemia coculture systems, pharmacological inhibition of LILRB4 restored antitumor immune activity, enhanced IFN-γ and IL-2 production, increased cytotoxic T-cell activation, and reduced tumor cell viability. GL-4512 additionally demonstrated favorable pharmacokinetic and safety properties supporting oral in vivo administration. In immunocompetent CT26 syngeneic colorectal tumors, once-daily oral treatment significantly suppressed tumor growth and enhanced intratumoral immune activation. Collectively, these findings establish LILRB4 as a tractable target for direct small molecule immunomodulation and support therapeutic targeting of suppressive myeloid immune checkpoints for cancer using nonbiologic modalities.

PMID 42503804
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