Stereochemistry | ACHIRAL |
Molecular Formula | C7H9ClO6P2S |
Molecular Weight | 318.608 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O
InChI
InChIKey=DKJJVAGXPKPDRL-UHFFFAOYSA-N
InChI=1S/C7H9ClO6P2S/c8-5-1-3-6(4-2-5)17-7(15(9,10)11)16(12,13)14/h1-4,7H,(H2,9,10,11)(H2,12,13,14)
Molecular Formula | C7H9ClO6P2S |
Molecular Weight | 318.608 |
Charge | 0 |
Count |
MOL RATIO
1 MOL RATIO (average) |
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Tiludronic acid is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates. Tiludronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and clodronate. Tiludronate affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the tiludronate that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface. Tiludronic acid is marketed under the tradename Skelid. In vitro studies indicate that tiludronate disodium acts primarily on bone through a
mechanism that involves inhibition of osteoclastic activity with a probable reduction in the
enzymatic and transport processes that lead to resorption of the mineralized matrix.
Bone resorption occurs following recruitment, activation, and polarization of osteoclasts.
Tiludronate disodium appears to inhibit osteoclasts through at least two mechanisms: disruption
of the cytoskeletal ring structure, possibly by inhibition of protein-tyrosine-phosphatase, thus
leading to detachment of osteoclasts from the bone surface and the inhibition of the osteoclastic proton pump. SKELID is indicated for treatment of Paget's disease of bone (osteitis deformans).
Originator
Approval Year
Cmax
AUC
Doses
AEs
Sourcing
PubMed
Sample Use Guides
A single 400-mg daily oral dose of SKELID (Tiludronic acid), taken with 6 to 8 ounces of plain water
only, should be administered for a period of 3 months. Beverages other than plain water
(including mineral water), food (see below), and some medications. Patients should not lie down for at least 30 minutes after taking this medication. SKELID should not be taken within 2 hours of food.
Route of Administration:
Oral
The ability of tiludronate to inhibit proton transport was 5-fold higher in kidney-derived chicken vesicles (IC50 = 1.1 mM) and 10,000-fold higher in vesicles derived from chicken osteoclasts (IC50 = 466 nM). Tiludronate also potently inhibited proton transport in yeast microsomal preparations (IC50 = 3.5 uM) and inhibited the activity of purified yeast V-ATPase.