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clodronate disodium (Abioklad / Mebonat / Ostac)

✓ Approved

Abiogen Pharma S.p.A. · SLC17A9 · 小分子

什么是 clodronate disodium？

clodronate disodium 是一种小分子，由Abiogen Pharma S.p.A.研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intraarterial Injection、Intramuscular (IM) Injection。

药物档案

商品名Abioklad, Mebonat, Ostac
公司Abiogen Pharma S.p.A.
药物类别小分子
分子靶点SLC17A9
给药途径Injectable (Others), Intraarterial Injection, Intramuscular (IM) Injection
状态Approved
来源： ClinicalTrials.gov, Abiogen Pharma S.p.A.

作用机制

分子靶点

clodronate disodium 作用于 1 个分子靶点：

SLC17A9solute carrier family 17 member 9 (POROK8, VNUT)
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

clodronate disodium 针对 6 个适应症，涉及 3 个治疗领域。

治疗领域疾病/病症分期
Endocrine disordersHypercalcaemia of malignancy✓ Approved
Musculoskeletal and connective tissue disordersMusculoskeletal pain✓ Approved
Musculoskeletal and connective tissue disordersOsteoarthritis✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Cancer pain✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Breast cancerPhase III

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相关研究文献

PubMedPractical radiation oncology2026-10-26

Practical considerations of gadoxetate disodium contrast in MRI-guided liver SBRT for primary and secondary liver tumors: optimizing image quality and patient throughput.

Kassardjian Ari A AA, Maraghechi Borna B, Shi Chengyu C, Ai Huisi H et al.

Optimal implementation of gadoxetate disodium injection (GDI) in liver-directed MR-guided online adaptive radiotherapy (MRgART) remains poorly characterized. Herein, we evaluated the impact of GDI on physician-reported imaging metrics and quantitative contouring variability during liver MRgART planning. Patients were scanned using a 0.35T MRI onboard the MR-guided LINAC. Pre- and post-contrast TRUFI images were captured at multiple timepoints up to 30 minutes (5-10-minute intervals) following GDI. Four radiation oncologists independently scored each tumor on a 5-point scale (1: poor; 5: excellent) evaluating imaging metrics, such as tumor visualization, border delineation, and image degradation from artifacts. Responses were stratified into pre-contrast, "early" post-contrast (1-15 minutes), and "late" post-contrast (20-30 minutes). Physicians then contoured gross tumor volume (GTV) for 6 patients with either optimal or non-optimal image characteristics. Inter- and intra-observer variability was assessed using Sørensen-Dice coefficient (DICE), Hausdorff distance (HD), volume of tumor not treated (VTNT), and volume of healthy liver erroneously treated (VHL). Comparisons were performed using Mann-Whitney U-test or Wilcoxon Signed-Rank test, as applicable. Twenty-three patients with 37 total liver tumors were treated using MRgART (median 50 Gy; 3-5 fractions). Late post-contrast imaging significantly improved tumor visualization (4.45) compared to early post-contrast (3.73; p<0.001) and pre-contrast (3.25; p<0.001). Late post-contrast also significantly improved border delineation (4.38) versus early post-contrast (3.58; p<0.001) and pre-contrast (3.06; p<0.001). In 6 patients selected for contouring analysis, DICE increased from 0.75 to 0.92 (p<0.01) and HD90 decreased from 4.18 mm to 2.00 mm (p<0.01) when GDI was helpful (n=3). Across all 6 patients, median VTNT significantly decreased from 3.68 cm3 to 0.68 cm3 (p<0.001). GDI administration 20-30 minutes prior to MRgART planning significantly enhances both physician-reported image quality and quantitative contouring accuracy. Its use should be considered in MRgART workflows to minimize potential geographic miss and optimize treatment delivery.

PMID 42933730
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PubMedCancer letters2026-10-26

MUC16 drives macrophage-mediated immunosuppression in pancreatic cancer.

Rajesh Christabelle C, Sagar Satish S, Huang Ying Y, Mundry Clara S CS et al.

Mucin-16 (MUC16) is overexpressed in >60% of pancreatic ductal adenocarcinoma (PDAC) cases and correlates with poor outcomes, yet its role in regulating tumor-immune interactions remains incompletely defined. Using KPC and KPC-MUC16 knockout (KPC-MUC16KO) genetically engineered and orthotopic mouse models, we show that loss of MUC16 markedly reduces tumor burden and reprograms the tumor microenvironment (TME) toward a less immunosuppressive state. MUC16 deficiency significantly decreased CD206+ and Ym1/2+ M2-like macrophages, increased the M1/M2 ratio, and improved survival. Cytokine profiling identified CCL2 and Serpin-E1 as MUC16- dependent secreted factors that promote macrophage recruitment and polarization; neutralization of these cytokines reduced macrophage migration in vitro. Bone marrow-derived macrophages (BMDM) exposed to MUC16-expressing tumor cells or conditioned media adopted a CD206+Arg1+ M2-like phenotype, whereas MUC16KO tumor signals favored inflammatory CD86+iNOS+ M1-like polarization. Macrophage depletion using clodronate liposomes significantly impaired tumor growth in MUC16-competent tumors but had minimal effect in KPC-MUC16KO tumors, indicating dependence on macrophage-mediated immunosuppression in the former group. Spatial transcriptomics revealed a globally distinct TME in MUC16KO tumors, including enhanced antigen-presentation programs, increased complement activation, and fibroblast states skewed toward pro-inflammatory signaling. These findings establish MUC16 as a key orchestrator of macrophage-driven immunosuppression in PDAC and support therapeutic strategies combining MUC16-targeted interventions with TME-reprogramming approaches.

PMID 42933591
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PubMedJournal of hazardous materials2026-10-26

A multifunctional Ce(IV)-based coagulant with integrated oxidation and adsorption for efficient removal of diverse arsenic species.

He Jiaojie J, Cai Qingwang Q, Yao Shiyang S, Wang Shiqi S et al.

Arsenic contamination is widespread in groundwater and surface water, with species including As(V), As(III), and organic arsenic. This study developed a Ce(IV)-based coagulant, CAN, with dual adsorption and oxidation capabilities for arsenic removal. For organic arsenic, CAN outperformed PAC in removing p-arsanilic acid (p-ASA) and disodium methylarsonate (DSMA); for roxarsone (ROX), CAN achieved > 99% removal at only 1/8 of the PAC dosage. The large ionic radius and high coordination number of Ce(IV) enable stronger binding to organic arsenic ligands via inner-sphere As-O-Ce complexation, overcoming steric hindrance that limits Al(III). For As(III), Ce(IV) exhibits oxidation-adsorption-coagulation synergy, converting As(III) to As(V) and immobilizing it in situ. To further optimize As(III) removal, pre-hydrolyzed CANB (B>0) was synthesized; with pre-ozonation, it reached > 96% efficiency and residual Ce of 0.006-0.024 mg/L, due to flower-like nanocrystal clusters. CAN hydrolysates are mainly Ce4 and Ce6 species, forming large flocs (D50 > 160-200 μm) and a loose, porous cake layer in the coagulation-ultrafiltration, sustaining ∼70% membrane flux (J/J₀). In real groundwater, CAN resisted competing ions and maintained high removal. Overall, the combined oxidation, adsorption, and coagulation functions of Ce(IV) salts broaden their applications and provide new strategies for treating water containing heavy metal oxyanions.

PMID 42933101
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PubMediScience2026-10-25

Intestinal microbiota-associated LysoPC(16:0) promotes endometriosis via PPARγ-mediated M2 macrophage polarization and IL-10 secretion.

Li Na N, Yuan Ming M, Jin Xueyang X, Jiao Xue X et al.

Both gut microbiota dysbiosis and altered pelvic immune microenvironment have been linked to endometriosis (EM), but the metabolites connecting the two remain undefined. Combining 16S rDNA sequencing with non-targeted metabolomics in a murine EM model, we found altered gut microbiota composition alongside a marked rise in peritoneal lysophosphatidylcholine (LysoPC(16:0)), linked to the microbiota shift by correlation analysis and fecal transplantation. LysoPC(16:0) promoted M2 macrophage polarization through peroxisome proliferator-activated receptor gamma (PPARγ), an effect observed in two mouse strains. Clodronate-mediated macrophage depletion blocked LysoPC(16:0)-driven lesion growth. LysoPC(16:0) further induced PPARγ-dependent IL-10 transcription, and IL-10 neutralization in vivo reduced lesion weight. Conditioned medium from LysoPC(16:0)-stimulated THP-1 macrophages promoted migration of primary endometrial stromal cells from patients with EM, an effect reversed by GW9662 or IL-10 neutralization. Together, these results outline a gut microbiota-LysoPC(16:0)-PPARγ-M2-IL-10 axis in EM pathogenesis, a mechanistic and therapeutic target for future clinical study.

PMID 42920945
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PubMedDiagnostic microbiology and infectious disease2026-10-25

Evaluation of Ceftriaxone-Sulbactam-EDTA against Carbapenem-resistant Enterobacterales and non-fermenters: correlating in vitro susceptibility with molecular detection of carbapenemase genes by Xpert Carba-R.

Kulkarni Sughosh S, Gupta Anupam A, Patil Navya Pradeepgoud NP, Madalgi Radhika Kishor RK

Carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a major therapeutic challenge because of the increasing prevalence of multidrug resistance and carbapenemase production. Although Ceftriaxone-Sulbactam-Disodium EDTA (CSE) has demonstrated encouraging in vitro activity against multidrug-resistant Gram-negative pathogens, evidence regarding its activity against carbapenem-resistant isolates and its relationship with carbapenemase genotype remains limited. This study thus evaluated the in vitro activity of CSE against CR-GNB and correlated the relationship between phenotypic susceptibility and carbapenemase genotype. A total of 208 non-duplicate carbapenem-resistant clinical isolates comprising Enterobacterales and non-fermenting Gram-negative bacilli were recovered from patients admitted to a tertiary care centre. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disk diffusion method, and carbapenemase genes (blaNDM, blaKPC, blaOXA-48, blaIMP and blaVIM) were detected using the Xpert® Carba-R assay. Overall, CSE demonstrated 65.9% susceptibility, with a combined susceptible-intermediate rate of 88.5%. Acinetobacter baumannii exhibited the highest susceptibility (85.5%), whereas Pseudomonas aeruginosa showed the lowest susceptibility (23.8%). Carbapenemase genes were detected in 72.6% of isolates, with blaNDM (60.6%) and blaOXA-48 (42.8%) predominating; co-harbouring of blaNDM and blaOXA-48 was the most frequent genotypic profile (31.3%). Multivariable logistic regression demonstrated that isolates harbouring blaOXA-48 alone (adjusted odds ratio [aOR] 5.11; p = 0.008) and blaNDM + blaOXA-48 (aOR 3.24; p = 0.004) were independently associated with CSE susceptibility. CSE demonstrated substantial in vitro activity against CR-GNB despite extensive multidrug resistance. Integration of rapid molecular carbapenemase detection with phenotypic susceptibility testing may improve interpretation of antimicrobial susceptibility and support evidence-based therapeutic decision-making for carbapenem-resistant Gram-negative infections.

PMID 42925659
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PubMedFood chemistry: X2026-10-23

Effects of sodium dihydrogen phosphate (MSP) and disodium hydrogen phosphate (DSP) on the glycation of casein (CN).

Xu Shaohong S, Hu Xiaodong X, Sun Yushuo Y, Huang Xueni X et al.

This study investigated the effects of phosphate addition on the Maillard reaction in glycated casein. Results showed that phosphate (especially at 100 mM) promoted the accumulation of Maillard intermediates and final products, while suppressing protein aggregation and increasing free amino group content. Structural analysis indicated a shift toward a more disordered conformation, enhancing reaction activity. Notably, specific phosphate treatments differentially modulated glycation sites and volatile compound formation; MSP significantly reduced aldehyde, ketone, and alcohol generation, contributing to flavor stability, whereas DSP showed limited effects. Phosphate thus plays a dual role by promoting early reaction stages and selectively modulating final product profiles, offering insights for controlling Maillard reaction and flavor in protein processing.

PMID 42908894
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