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clodronate disodium (Bonefos / Clastoban)

✓ Approved

Takeda · SLC17A9 · 小分子

什么是 clodronate disodium？

clodronate disodium 是一种小分子，由Takeda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Bonefos, Clastoban
公司Takeda
药物类别小分子
分子靶点SLC17A9
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Takeda

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 2 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Endocrine disordersHypercalcaemia of malignancy✓ Approved
Musculoskeletal and connective tissue disordersOsteoporosis✓ Approved

相关研究文献

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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PubMedEuropean journal of clinical pharmacology2026-10-23

Clinical safety, tolerability, and efficacy of fospropofol disodium for sedation: a systematic review.

Yan Caiyi C, Jiao Bo B, Xu Xiaolin X, Chen Guo G et al.

Fospropofol disodium (fospropofol) is a water-soluble prodrug of propofol with a distinct pharmacological and tolerability profile. However, evidence regarding the safety, tolerability, and efficacy of fospropofol across broader sedation contexts and different comparators remains insufficiently synthesized. This systematic review summarized current research findings on fospropofol to clarify its clinical role and guide future research. This systematic review was registered prior to initiation (PROSPERO CRD42023477740). Comprehensive searches were performed in PubMed, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, ClinicalTrials.gov from inception to 26 August 2026. Randomized controlled trials (RCTs) evaluating fospropofol for sedation and reporting extractable efficacy or safety outcomes were eligible. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated according to the GRADE approach. Meta-analysis was performed for clinically comparable evidence groups, with other findings synthesized according to SWiM principles. This systematic review included 10 original studies, comprising six procedural-sedation trials and four trials for ICU sedation. Quantitative synthesis was conducted for two comparable evidence groups, whereas the remaining outcomes were synthesized narratively. In three endoscopic procedural-sedation trials, fospropofol 6.5 mg/kg achieved a higher sedation success than 2 mg/kg (RR 3.27, 95% CI 2.62-4.08). In mechanically ventilated ICU patients, hypotension risk did not clearly differ between fospropofol and propofol (RR 0.93, 95% CI 0.67-1.28). Procedural studies showed a dose-dependent pattern in sedation efficacy, whereas ICU studies generally reported comparable target-sedation attainment between fospropofol and comparator sedatives. Paresthesia/pruritus was commonly reported, while rates of cardiorespiratory adverse events varied across settings and doses and showed no consistent comparative advantage for fospropofol. Evidence for injection pain and satisfaction was limited. Certainty of evidence ranged from high to very low, mainly because of risk of bias and imprecision. Fospropofol can provide effective sedation across procedural and ICU settings, but its efficacy and safety profiles vary according to dose, comparator, and clinical setting. Higher doses may improve procedural-sedation efficacy but may also increase adverse effects in some settings. Current evidence does not establish a consistent cardiorespiratory safety advantage for fospropofol over other sedatives, and further adequately powered randomized trials are needed to clarify its comparative safety and optimal clinical role.

PMID 42911252
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PubMedThe journal of physical chemistry. B2026-10-23

Microscopic Dynamic Mechanisms of Surfactant-Induced Skin Irritation.

Xu Jingwen J, Zhou Kangfu K, Wang Feifei F, Ye Zhicheng Z et al.

Surfactants are essential components of detergents and personal care products due to their unique amphiphilic structure. However, the mechanism underlying surfactant-induced skin irritation remains unclear. This study systematically combined experiments with molecular dynamics (MD) simulations to investigate this mechanism, focusing on three surfactant systems including pure disodium cocoyl glutamate (DCG), a DCG/sodium lauroyl aspartate/rhamnolipid mixture (DCG/SLA/GL), and a DCG/SLA/GL/cocamidopropyl betaine mixture (DCG/SLA/GL/CAPB). Experimental results show that, among these systems, those with lower critical micelle concentration (CMC) form larger surfactant aggregates in the bulk phase and exhibit lower irritation in the HET-CAM assay. MD simulations reveal that free surfactants alter the conformation of ceramides (CER) and free fatty acids (FFA) by inserting into the lipid layer model, particularly affecting the longer tails of CER, and this insertion disrupts lipid packing and impairs the lipid layer's hydration capacity. More stable surfactant aggregates suppress the dissociation of individual surfactants, thereby reducing the insertion of free surfactants into the lipid layer. Surfactant aggregates tend to linger near the lipid-water interface and indirectly modulate the conformation of CER and FFA by interfacial perturbation, an effect substantially weaker than that of free surfactants at equivalent concentrations. For the studied systems, both free surfactants and aggregates influence lipid layer structure, but free surfactant insertion appears to be the dominant contributor to lipid layer disruption within the present model. More stable and compact aggregates, such as those formed in the DCG/SLA/GL/CAPB system, exert a significantly smaller impact on the lipid layer among the three systems studied. This study proposes a plausible microscopic mechanism linking surfactant aggregation behavior to irritation for the tested formulations, providing theoretical insights for the rational design of lower-irritation surfactant systems.

PMID 42915330
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PubMedJournal of ethnopharmacology2026-10-22

Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.

Huo Wanhua W, Hou Xuyang X, Huang Yiying Y, Li Zuming Z et al.

Sepsis-associated acute lung injury (SA-ALI) has high mortality and limited therapies.Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization. To evaluate the protective effects of THCQ pretreatment against LPS-induced SA-ALI and examine associated changes in gut microbiota, succinate levels, SUCNR1-PKA-CREB signaling and macrophage polarization. A murine SA-ALI model was induced by intraperitoneal LPS. Lung injury, inflammatory cytokines (IL-1β, TNF-α), and M1/M2 polarization were assessed. Gut microbiota was analyzed by 16S rRNA sequencing. Succinate levels, SUCNR1, and PKA-CREB signaling were measured. Microbiota dependence was tested using antibiotic depletion, fecal microbiota transplantation (FMT) from THCQ-treated donors, exogenous succinate, and macrophage depletion with clodronate liposomes. THCQ pretreatment attenuated lung injury, reduced IL-1β and TNF-α levels, and shifted pulmonary macrophage polarization toward an M2-like phenotype. These effects were accompanied by altered gut microbiota composition, a lower abundance ratio of bacterial families grouped in the exploratory succinate-metabolism analysis, reduced serum and pulmonary succinate levels, lower SUCNR1 expression, and increased PKA/CREB phosphorylation. Antibiotic treatment attenuated the protective responses to THCQ, while FMT from THCQ-treated donors reproduced improvements in lung injury. Exogenous succinate attenuated THCQ-mediated protection. Clo-Lipo treatment reduced the proportions of alveolar and interstitial macrophages and markedly attenuated the protective effects of THCQ. THCQ treatment protects against SA-ALI and suppresses M1-like macrophage polarization. These effects are accompanied by changes in gut microbiota composition, reduced succinate levels, and altered SUCNR1-PKA-CREB signaling. Together, the findings support a role for gut microbiota-metabolism-immune interactions in the protective effects of THCQ.

PMID 42906799
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