Clodronate disodium tetrahydrate (Disodium clodronate tetrahydrate) is a first-generation bisphosphonate that has anti-osteoporotic and anti~inflammatory effects and may be utilized in pain relief research. Clodronate disodium tetrahydrate is a selective, highly efficient, reversible, Cl-competitive vesicular nucleotide transporter (VNUT) blocker with IC50 of 15.6 nM. Clodronate disodium tetrahydrate can inhibit the release of vesicular ATP from neurons and relieve chronic neuropathic pain and inflammatory pain.

Physicochemical Properties

Molecular Formula	CH2CL2NA2O6P2
Molecular Weight	288.8560
Exact Mass	359.892
CAS #	88416-50-6
Related CAS #	Clodronic acid disodium salt;22560-50-5;Clodronic acid;10596-23-3
PubChem CID	23724874
Appearance	White to off-white solid powder
LogP	1.049
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	2
Heavy Atom Count	17
Complexity	206
Defined Atom Stereocenter Count	0
InChi Key	XWHPUCFOTRBMGS-UHFFFAOYSA-L
InChi Code	InChI=1S/CH4Cl2O6P2.2Na.4H2O/c2-1(3,10(4,5)6)11(7,8)9;;;;;;/h(H2,4,5,6)(H2,7,8,9);;;4*1H2/q;2*+1;;;;/p-2
Chemical Name	disodium;[dichloro-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate;tetrahydrate
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Clodronate disodium tetrahydrate is a first-generation bisphosphonate that acts by blocking VNUT, a crucial molecule that starts purinergic chemical events, to greatly reduce neuropathic and neuropathic pain unrelated to disruptive disorders [1]. connection as a medication that resists bone absorption [2].
ln Vivo	By blocking VNUT, clodronate tetrahydrate (10 mg/kg; IV) reduces accommodative discomfort [1]. Disodium clodronate tetrahydrate inhibits VNUT, which reduces accommodative pain [1].
Animal Protocol	Animal/Disease Models: C57BL/6 mice (22-30 g) [1] Doses: 10 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: Reduce inflammatory pain caused by carrageenan or complete Freund's adjuvant (CFA) .
References	[1]. Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain. Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):E6297-E6305. [2]. Clodronate: A Vesicular ATP Release Blocker. Trends Pharmacol Sci. 2018 Jan;39(1):13-23.
Additional Infomation	Disodium clodronate tetrahydrate is the tetrahydrate of the disodium salt of clodronic acid. It inhibits bone resorption and soft tissue calcification, and is used as an adjunct in the treatment of severe hypercalcaemia associated with malignancy, and in the management of osteolytic lesions and bone pain associated with skeletal metastases. It has a role as a bone density conservation agent. It is a hydrate and a one-carbon compound. It contains a clodronic acid disodium salt. Clodronate Disodium is the disodium salt of a nitrogen-free bisphosphonate analog of naturally occurring pyrophosphate. Clodronate binds to calcium and inhibits osteoclastic bone resorption and hydroxyapatite crystal formation and dissolution, resulting in a reduction of bone turnover. This agent may control malignancy-associated hypercalcemia, inhibit osteolytic bone metastasis and decrease pain. A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.

Solubility Data

Solubility (In Vitro)	H2O : ~125 mg/mL (~346.34 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 25 mg/mL (69.27 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.4619 mL	17.3094 mL	34.6188 mL
	5 mM	0.6924 mL	3.4619 mL	6.9238 mL
	10 mM	0.3462 mL	1.7309 mL	3.4619 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.