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clodronate disodium (Bonefos / Clastoban)

✓ Approved

Takeda · SLC17A9 · Small Molecule

What is clodronate disodium?

clodronate disodium is a small molecule developed by Takeda. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesBonefos, Clastoban
CompanyTakeda
Drug ClassSmall Molecule
Molecular TargetSLC17A9
RouteOral (PO)
StatusApproved

Mechanism of Action

Molecular Targets

clodronate disodium acts on 1 molecular target:

SLC17A9solute carrier family 17 member 9 (POROK8, VNUT)
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Therapeutic Indications

clodronate disodium is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Endocrine disordersHypercalcaemia of malignancy✓ Approved
Musculoskeletal and connective tissue disordersOsteoporosis✓ Approved

Related Research Articles

PubMedRadiology case reports2026-07-24

Calcified liver metastases from medullary thyroid carcinoma in a Multiple Endocrine Neoplasia Type 2A patient.

Tang Chun Lang CL, Ng Fung Him FH

Calcified liver lesions encompass a broad differential diagnosis, with calcified hepatic granulomas being the most frequently encountered. We report a rare case of calcified hepatic metastases that were initially misinterpreted as hepatic granulomas. A 51-year-old patient with known Multiple Endocrine Neoplasia Type 2A had a history of medullary thyroid carcinoma treated surgically with total thyroidectomy and bilateral neck dissection in 2005. Serial CT scans obtained between 2010 to 2025 showed a few progressively enlarging calcified hepatic lesions that were initially misinterpreted as calcified hepatic granulomas. Due to persistently elevated tumor markers, a 18F-DOPA PET/CT was performed, which demonstrated increased radiotracer uptake of these lesions, suggesting they are metabolically active hepatic metastasis. MRI with Gadoxetate disodium also showed finding suggestive of hypervascular hepatic metastases. Diagnostic laparoscopy and histopathology confirmed the diagnosis of calcified hepatic metastasis from medullary thyroid carcinoma. This case emphasizes that hepatic calcifications, though often presumed benign, may occasionally represent other underlying pathologies such as metastatic disease. We hope to describe the imaging features of calcified hepatic metastases from medullary thyroid carcinoma, and the differentials of calcified hepatic lesions.

PubMedFrontiers in pharmacology2026-07-23

A preliminary exploration of the role and mechanisms of CD93 in promoting the malignant progression of head and neck squamous cell carcinoma.

Zhou Jing J, Zhang Yao Y, Zhang Nian N, Liao Yan Y et al.

Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an immunosuppressive microenvironment. Although CD93 promotes angiogenesis in tumor endothelial cells, its role in HNSCC tumor cells and the impact of CD93-mediated regulation of tumor cells on the tumor microenvironment are unclear. This study investigates whether CD93 promotes the malignant progression of HNSCC by enhancing tumor cell malignancy and contributing to macrophage-associated and angiogenic remodeling of the tumor microenvironment, elucidating the underlying mechanisms. Bioinformatics analyses assessed CD93 expression, clinical relevance, immune infiltration, and signaling pathways in HNSCC. CD93 expression was validated in clinical specimens and cell lines. CD93 knockdown and overexpression models were used to examine invasion, migration, proliferation, and epithelial-mesenchymal transition (EMT). Conditioned media from CD93-modulated tumor cells were applied to THP-1-derived macrophages and HUVECs to assess macrophage-associated markers and endothelial tube formation. Wnt/β-catenin signaling was pharmacologically activated or inhibited. Xenograft growth and macrophage depletion were evaluated in BALB/c nude mice. Protein-protein docking was used to explore predicted spatial compatibility between CD93 and receptor-proximal Wnt pathway components. CD93 was upregulated in HNSCC and associated with poor prognosis and an immunosuppressive, pro-angiogenic TME. CD93 knockdown inhibited invasion, migration, proliferation, EMT-associated changes, CD206 expression, changes in macrophage-associated markers, and endothelial tube formation, whereas CD93 overexpression produced opposite effects. CD93 expression was associated with Wnt/β-catenin activation; CHIR99021 reversed the effects of CD93 knockdown, whereas XAV939 attenuated changes induced by CD93 overexpression. In vivo, CD93 knockdown suppressed xenograft growth, proliferation, angiogenesis, EMT-associated changes, CD206-positive macrophage-associated signals, and β-catenin expression. Clodronate liposome-mediated macrophage depletion reduced HSC3-shNC tumor growth and narrowed the difference between HSC3-shNC and HSC3-shCD93 tumors. Docking analysis indicated that CD93 showed the most favorable predicted spatial compatibility with LRP6 E1E2 among the tested Wnt receptor-related components. CD93 may promote HNSCC progression by enhancing tumor-cell aggressiveness and tumor microenvironment remodeling, at least partly through Wnt/β-catenin-related signaling. Docking analysis provides a preliminary structural hypothesis for a potential CD93-LRP6 E1E2 spatial association. CD93 may represent a prognostic biomarker and candidate therapeutic target in HNSCC.

PubMedActa crystallographica. Section C, Structural chemistry2026-07-22

Structural characterization of a series of alkali metal coordination polymers of gallic acid.

Kreider-Mueller Ava A, Golen James A JA, Morris Thomas A TA, Manke David R DR

This work aims to reveal the rich coordination chemistry of gallic acid (H4GA), a ubiquitous plant polyphenol, toward alkali metals. To date, only three crystal structures have been reported in the literature that feature an alkali metal, namely Na, K, and Cs, in combination with a deprotonated form of gallic acid. Of those three structures, only the Cs compound, which is an alkali metal-based coordination polymer of gallic acid, features direct coordination between the deprotonated acid and the alkali metal center. This work reports the crystal structures of six new alkali metal-based coordination polymers of gallic acid, including poly[diaqua(μ-3,4,5-trihydroxybenzoato)(μ-3,4,5-trihydroxybenzoic acid)lithium], [Li(C7H5O5)(C7H6O5)(H2O)2]n, 1, poly[diaqua-μ-aqua-(μ-3,4,5-trihydroxybenzoato)sodium], [Na(C7H5O5)(H2O)3]n, 2, poly[[tetraaquabis(μ-3,4,5-trihydroxybenzoato)bis(3,4,5-trihydroxybenzoic acid)disodium] tetrahydrate], {[Na2(C7H5O5)2(C7H6O5)2(H2O)4]·4H2O}n, 3, poly[[μ-acetato-(μ-3,4,5-trihydroxybenzoic acid)potassium] monohydrate], {[K(C7H6O5)(C2H3O2)]·H2O}n, 4, poly[[μ-acetato-(μ-3,4,5-trihydroxybenzoic acid)rubidium]monohydrate], {[Rb(C7H6O5)(C2H3O2)]·H2O}n, 5, poly[diaquabis(μ-3,4,5-trihydroxybenzoato)-bis(μ-3,4,5-trihydroxybenzoic acid)dicaesium], [Cs2(C7H5O5)2(C7H6O5)2(H2O)2]n, 6. Single crystals suitable for X-ray diffraction studies were obtained from ethanolic solutions of H4GA that were treated with a series of aqueous solutions of alkali metal acetates, MOAc (M = Li, Na, K, Rb, and Cs). Seven different molar ratios of MOAc to H4GA (1:1, 1:2, 1:3, 1:4, 2:1, 3:1, and 4:1) were tested for each reaction combination. The dimensionality of the six coordination polymers reported varies across this series of compounds, ranging from one-dimensional chains (3) to two-dimensional sheets (1 and 2), and complex three-dimensional coordination network solids (4-6). Interestingly, the K (4) and Rb (5) compounds are isomorphous, while the sodium salt crystallizes in two forms (2 and 3).

PubMedMolecular imaging and biology2026-07-21

Pharmacokinetic Modeling of Hepatospecific MRI Contrast Agent Flux in Large Animal Models by Dynamic Contrast-Enhanced MRI.

Latourette Matthew T MT, Hix Jeremy M L JML, Huang Jie J, Mallett Christiane L CL et al.

Evaluate the feasibility of using dogs and a pig as translational models for assessing hepatic flux of hepatospecific gadolinium-based contrast agents using dynamic contrast-enhanced MRI (DCE-MRI). DCE-MRI was performed with hepatospecific agents, gadoxetate disodium (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA), and non-hepatospecific agents. Two validated pharmacokinetic models were applied: a single-input reference region model and a dual-input model using arterial and venous blood signals. In dogs, hepatic enhancement rose rapidly and plateaued after Gd-EOB-DTPA administration, with minimal decline over an hour. In the pig, both hepatospecific agents showed a rapid rise, blunt peak, and gradual decline. The single-input model revealed significantly higher uptake rates for hepatospecific agents, confirming its sensitivity to hepatocyte uptake. The dual-input model effectively distinguished contrast agent dynamics in dogs and showed promise in the pig. In this feasibility study, the enhancement dynamics observed and pharmacokinetic estimates computed in both dogs and a pig fell broadly within ranges reported in human studies, supporting their potential utility as translational large-animal models. Definitive comparison of species similarity to humans will require direct paired evaluation under matched conditions.

PubMedSoft matter2026-07-21

Photoresponsive, ionically cross-linked chitosan-azobenzene capsules for controlled cargo release.

Zaib Mehmoona M, Hill Christopher T CT, Farooq Muhammad Umar MU, Tuck Kellie L KL et al.

Photoresponsive capsules capable of controlled cargo release under mild conditions are of growing interest in soft matter and colloidal systems. In this study, we report the fabrication of visible light responsive, ionically cross-linked chitosan microcapsules using a tetra-ortho-fluoro azobenzene dicarboxylate cross-linker: disodium (E)-4,4'-(diazene-1,2-diyl)bis(3,5-difluorobenzoate) (NaFDAB) and chitosan. Chitosan was selected as a biocompatible and biodegradable shell material, and NaFDAB was added as a cross-linker to provide stability via strong ionic interactions with protonated chitosan amines, while also providing visible-light photoresponsiveness to the capsules. Capsules were prepared via a simple oil-in-water emulsion method, yielding spherical capsules with mechanically stable shells as confirmed by optical microscopy, field emission scanning electron microscopy (FE-SEM), and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. UV-Vis spectroscopy demonstrated reversible trans-cis photoisomerisation of NaFDAB under green and blue light illumination. Nile Red as a model cargo was used to explore controlled release and monitored using fluorescence spectroscopy. Release occurred only under green-light irradiation, while minimal release was observed under ambient light conditions. Encapsulation efficiencies of approximately 45-50% were achieved. While controlled release of up to ∼28% was observed under green-light irradiation, pulsed irradiation experiments revealed controllable on-off release behaviour, consistent with diffusion-controlled transport governed by light-modulated shell permeability. These findings demonstrate a mild, effective and scalable strategy for photo-controlled cargo delivery using visible light.

PubMedJournal of magnetic resonance imaging : JMRI2026-07-18

Editorial for "Effect of 37°C Pre-Warmed Versus Room Temperature Gadoxetic Acid Disodium Contrast Medium on Patient Comfort and Image Quality in Liver MRI: A Prospective, Double-Blind, Self-Controlled Before-and-After Study".

Torkzad Michael R MR, Mittal Pardeep P

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