Name | disodium dihydrogen (dichloromethylene)diphosphonate |
Synonyms | DMDP CL2MDP Clodronate CLODRONATE DISODIUM CLODRONIC ACID DISODIUM SALT DICHLOROMETHYLENEDIPHOPHONIC ACID DISODIUM SALT Dichloromethylenediphosphonic Acid Disodium Salt DICHLOROMETHYLENEDIPHOSPHONIC ACID DISODIUM SALT disodium dihydrogen (dichloromethylene)diphosphonate disodium (dichloromethanediyl)bis[hydrogen (phosphonate)] Disodium dichloromethylenebis(hydrogenphosphonate) tetrahydrate |
CAS | 22560-50-5 |
EINECS | 245-078-9 |
InChI | InChI=1/CH4Cl2O6P2.2Na/c2-1(3,10(4,5)6)11(7,8)9;;/h(H2,4,5,6)(H2,7,8,9);;/q;2*+1/p-2 |
InChIKey | HJKBJIYDJLVSAO-UHFFFAOYSA-L |
Molecular Formula | CH2Cl2Na2O6P2 |
Molar Mass | 288.86 |
Melting Point | >330°C |
Boling Point | 474.7°C at 760 mmHg |
Flash Point | 240.9°C |
Solubility | Freely soluble in water, practically insoluble in ethanol (96 per cent), slightly soluble in methanol. |
Vapor Presure | 2.55E-10mmHg at 25°C |
Appearance | Solid |
Color | White to Off-White |
Storage Condition | room temp |
In vitro study | Clodronate significantly reduced the overall survival of J774 cell cultures with an EC50 of 300 μm, while liposome-encapsulated Clodronate reduced the overall survival of J774 cell cultures with an EC50 of 1 μm. Clodronate and liposome-encapsulated Clodronate metabolize to a non-hydrolyzable analog of adenosine triphosphate (ATP), adenosine 5 '-(β,γ-dichloromethylene) triphosphate, it can be rapidly detected by protein liquid chromatography in J774 cell extracts. Clodronate induces osteoclast apoptosis in vitro. Clodronate, when administered in liposomes, also induces apoptosis in mouse peritoneal macrophages in vitro and in mouse hepatic macrophages in vivo, however, it has no effect on murine macrophage-like RAW-264 cells. Clodronate delivered by liposomes to macrophages will kill these cells as a result of intracellular accumulation and irreversible metabolic damage. According to the treatment protocol, Clodronate encapsulated in liposomes (clodrolip) was used in F9 teratocarcinoma mice and a mouse model of human A673 rhabdomyosarcoma, it was effective in reducing phagocytes to significantly inhibit tumor growth by 75 to> 92%. Clodronate, a nitrogen-deficient bisphosphonate, has no inhibitory effect on protein prenylation, but can be metabolized intracellularly to an ATP analog, beta-gamma-methylene(AppCp type), this is a cytotoxic effect on macrophages in vitro. Clodronate is metabolized to AppCCl(2)p, which then inhibits mitochondrial oxygen consumption by participating in a mechanism that competitively inhibits the ADP / ATP translocase. |
WGK Germany | 3 |
RTECS | SZ7640700 |
HS Code | 29319090 |
bisphosphonate drugs | clodronate disodium is the first generation bisphosphonate drug for the treatment of osteoporosis, bisphosphonates (bisphosphonates,BPs) is a new class of drugs for various bone diseases and calcium metabolic diseases. It can specifically combine with hydroxyphosphine in bone to inhibit osteoclast activity, thereby inhibiting bone absorption. It is used to treat osteoporosis, osteitis deforming, hypercalcemia and bone pain caused by bone metastasis of malignant tumor. |
biological activity | Clodronate Disodium, a bisphosphonate, is an effective antiosteolytic agent that can inhibit bone resorption. |
Animal Model: | Male Lewis rats, aged 7 weeks |
Dosage: | 6.25, 12.5, and 25 mg/kg |
Administration: | P.o.; daily for 28 days |
Result: | Hindpaw swelling was significantly smaller than in adjuvant-arthritis (AA)-control at 25 mg/kg on days 21 and 28 (87 and 88% of AA-control, respectively) and at 12.5 mg/kg on day 28. |