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Identification
NameTiludronate
Accession NumberDB01133  (APRD01259)
TypeSmall Molecule
GroupsApproved, Vet Approved
DescriptionTiludronate is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates.
Structure
Thumb
Synonyms
Acide tiludronique
Acido tiludronico
Acidum tiludronicum
Tiludronate
Tiludronic acid
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
SkelidNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tiludronate Disodium
149845-07-8
Thumb
  • InChI Key: DKJJVAGXPKPDRL-UHFFFAOYSA-N
  • Monoisotopic Mass: 317.928359441
  • Average Mass: 318.608
DBSALT000411
Categories
UNII6PNS59HP4Y
CAS number89987-06-4
WeightAverage: 318.608
Monoisotopic: 317.928359441
Chemical FormulaC7H9ClO6P2S
InChI KeyDKJJVAGXPKPDRL-UHFFFAOYSA-N
InChI
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)
IUPAC Name
{[(4-chlorophenyl)sulfanyl](phosphono)methyl}phosphonic acid
SMILES
OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O
Pharmacology
IndicationFor treatment of Paget's disease of bone (osteitis deformans).
Structured Indications Not Available
PharmacodynamicsTiludronate 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.
Mechanism of actionThe bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. In vitro studies indicate that tiludronate 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 appears to inhibit osteoclasts by 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
HydroxylapatiteSmall moleculeyes
antagonist
Humannot applicabledetails
V-type proton ATPase catalytic subunit AProteinunknown
inhibitor
HumanP38606 details
Tyrosine-protein phosphatase non-receptor type 1Proteinunknown
inhibitor
HumanP18031 details
Related Articles
AbsorptionThe mean oral bioavailability in healthy male subjects is 6% after an oral dose equivalent to 400 mg tiludronic acid administered after an overnight fast and 4 hours before a standard breakfast. In single-dose studies, bioavailability was reduced by 90% when an oral dose equivalent to 400 mg tiludronic acid was administered with, or 2 hours after, a standard breakfast compared to the same dose administered after an overnight fast and 4 hours before a standard breakfast.
Volume of distributionNot Available
Protein bindingApproximately 90% bound to human serum protein (mainly albumin) at plasma concentrations between 1 and 10 mg/L.
Metabolism

In vitro, tiludronic acid is not metabolized in human liver microsomes and hepatocytes. There is no evidence that tiludronate is metabolized in humans.

Route of eliminationThe principal route of elimination of tiludronic acid is in the urine.
Half lifeHalf-life in healthy subjects is 50 hours following administration of a 400 mg single oral dose. Half-life in pagetic patients is about 150 hours following administration of 400 mg tiludronate a day for 12 days. In patients with renal insufficiency (creatinine clearance between 11 and 18 mL per minute [mL/min]), half-life is 205 hours from plasma after administration of a single, oral dose equivalent to 400 mg tiludronate.
Clearance
  • renal cl=10 mL/min [IV administration of 20-mg dose]
ToxicityBased on the known action of tiludronate, hypocalcemia is a potential consequence of overdose. In one patient with hypercalcemia of malignancy, intravenous administration of high doses (800 mg/day total dose, 6 mg/kg/day for 2 days) was associated with acute renal failure and death.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Tiludronate.Approved
AcetovanilloneThe risk or severity of adverse effects can be increased when Acetovanillone is combined with Tiludronate.Investigational
Acetylsalicylic acidThe serum concentration of Tiludronate can be decreased when it is combined with Acetylsalicylic acid.Approved, Vet Approved
AclarubicinAclarubicin may increase the hypocalcemic activities of Tiludronate.Investigational
AdapaleneThe risk or severity of adverse effects can be increased when Adapalene is combined with Tiludronate.Approved
Aluminum hydroxideThe serum concentration of Tiludronate can be decreased when it is combined with Aluminum hydroxide.Approved
Aluminum phosphateThe serum concentration of Tiludronate can be decreased when it is combined with Aluminum phosphate.Approved
AmikacinAmikacin may increase the hypocalcemic activities of Tiludronate.Approved, Vet Approved
AmrubicinAmrubicin may increase the hypocalcemic activities of Tiludronate.Approved, Investigational
AnisodamineThe risk or severity of adverse effects can be increased when Anisodamine is combined with Tiludronate.Investigational
annamycinannamycin may increase the hypocalcemic activities of Tiludronate.Investigational
AntipyrineThe risk or severity of adverse effects can be increased when Antipyrine is combined with Tiludronate.Approved
ApramycinApramycin may increase the hypocalcemic activities of Tiludronate.Experimental, Vet Approved
ApremilastThe risk or severity of adverse effects can be increased when Apremilast is combined with Tiludronate.Approved, Investigational
ArbekacinArbekacin may increase the hypocalcemic activities of Tiludronate.Approved
AzapropazoneThe risk or severity of adverse effects can be increased when Azapropazone is combined with Tiludronate.Withdrawn
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Tiludronate.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Tiludronate.Approved, Investigational
BenoxaprofenThe risk or severity of adverse effects can be increased when Benoxaprofen is combined with Tiludronate.Withdrawn
Betulinic AcidThe risk or severity of adverse effects can be increased when Betulinic Acid is combined with Tiludronate.Investigational
Bismuth SubcitrateThe serum concentration of Tiludronate can be decreased when it is combined with Bismuth Subcitrate.Approved
BromfenacThe risk or severity of adverse effects can be increased when Bromfenac is combined with Tiludronate.Approved
BucillamineThe risk or severity of adverse effects can be increased when Bucillamine is combined with Tiludronate.Investigational
CalciumThe serum concentration of Tiludronate can be decreased when it is combined with Calcium.Nutraceutical
Calcium AcetateThe serum concentration of Tiludronate can be decreased when it is combined with Calcium Acetate.Approved
Calcium carbonateThe serum concentration of Tiludronate can be decreased when it is combined with Calcium carbonate.Approved
Calcium ChlorideThe serum concentration of Tiludronate can be decreased when it is combined with Calcium Chloride.Approved
Calcium citrateThe serum concentration of Tiludronate can be decreased when it is combined with Calcium citrate.Approved
Calcium glubionateThe serum concentration of Tiludronate can be decreased when it is combined with Calcium glubionate.Approved
Calcium GluceptateThe serum concentration of Tiludronate can be decreased when it is combined with Calcium Gluceptate.Approved
Calcium gluconateThe serum concentration of Tiludronate can be decreased when it is combined with Calcium gluconate.Approved, Vet Approved
CarprofenThe risk or severity of adverse effects can be increased when Carprofen is combined with Tiludronate.Approved, Vet Approved, Withdrawn
CastanospermineThe risk or severity of adverse effects can be increased when Castanospermine is combined with Tiludronate.Experimental
CelecoxibThe risk or severity of adverse effects can be increased when Celecoxib is combined with Tiludronate.Approved, Investigational
ChloroquineThe risk or severity of adverse effects can be increased when Chloroquine is combined with Tiludronate.Approved, Vet Approved
ClonixinThe risk or severity of adverse effects can be increased when Clonixin is combined with Tiludronate.Approved
CurcuminThe risk or severity of adverse effects can be increased when Curcumin is combined with Tiludronate.Investigational
D-LimoneneThe risk or severity of adverse effects can be increased when D-Limonene is combined with Tiludronate.Investigational
DaunorubicinDaunorubicin may increase the hypocalcemic activities of Tiludronate.Approved
DeferasiroxThe risk or severity of adverse effects can be increased when Tiludronate is combined with Deferasirox.Approved, Investigational
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Tiludronate.Approved, Vet Approved
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Tiludronate.Approved
DihydrostreptomycinDihydrostreptomycin may increase the hypocalcemic activities of Tiludronate.Vet Approved
DoxorubicinDoxorubicin may increase the hypocalcemic activities of Tiludronate.Approved, Investigational
DroxicamThe risk or severity of adverse effects can be increased when Droxicam is combined with Tiludronate.Approved
DuvelisibThe risk or severity of adverse effects can be increased when Duvelisib is combined with Tiludronate.Investigational
E6201The risk or severity of adverse effects can be increased when E6201 is combined with Tiludronate.Investigational
EbselenThe risk or severity of adverse effects can be increased when Ebselen is combined with Tiludronate.Investigational
EpirizoleThe risk or severity of adverse effects can be increased when Epirizole is combined with Tiludronate.Approved
EpirubicinEpirubicin may increase the hypocalcemic activities of Tiludronate.Approved
EsomeprazoleThe therapeutic efficacy of Tiludronate can be decreased when used in combination with Esomeprazole.Approved, Investigational
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Tiludronate.Approved, Investigational
EtodolacThe risk or severity of adverse effects can be increased when Etodolac is combined with Tiludronate.Approved, Investigational, Vet Approved
EtofenamateThe risk or severity of adverse effects can be increased when Etofenamate is combined with Tiludronate.Approved
EtoricoxibThe risk or severity of adverse effects can be increased when Etoricoxib is combined with Tiludronate.Approved, Investigational
Evening primrose oilThe risk or severity of adverse effects can be increased when Evening primrose oil is combined with Tiludronate.Approved
exisulindThe risk or severity of adverse effects can be increased when exisulind is combined with Tiludronate.Investigational
FenbufenThe risk or severity of adverse effects can be increased when Fenbufen is combined with Tiludronate.Approved
FenoprofenThe risk or severity of adverse effects can be increased when Fenoprofen is combined with Tiludronate.Approved
Ferric CitrateThe serum concentration of Tiludronate can be decreased when it is combined with Ferric Citrate.Approved
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Tiludronate.Approved, Withdrawn
FlunixinThe risk or severity of adverse effects can be increased when Flunixin is combined with Tiludronate.Vet Approved
FlurbiprofenThe risk or severity of adverse effects can be increased when Flurbiprofen is combined with Tiludronate.Approved, Investigational
FramycetinFramycetin may increase the hypocalcemic activities of Tiludronate.Approved
GeneticinGeneticin may increase the hypocalcemic activities of Tiludronate.Experimental
GentamicinGentamicin may increase the hypocalcemic activities of Tiludronate.Approved, Vet Approved
GENTAMICIN C1AGENTAMICIN C1A may increase the hypocalcemic activities of Tiludronate.Experimental
HigenamineThe risk or severity of adverse effects can be increased when Higenamine is combined with Tiludronate.Investigational
HMPL-004The risk or severity of adverse effects can be increased when HMPL-004 is combined with Tiludronate.Investigational
Hygromycin BHygromycin B may increase the hypocalcemic activities of Tiludronate.Vet Approved
IbuprofenThe risk or severity of adverse effects can be increased when Ibuprofen is combined with Tiludronate.Approved
IbuproxamThe risk or severity of adverse effects can be increased when Ibuproxam is combined with Tiludronate.Withdrawn
IcatibantThe risk or severity of adverse effects can be increased when Icatibant is combined with Tiludronate.Approved
IdarubicinIdarubicin may increase the hypocalcemic activities of Tiludronate.Approved
IndomethacinThe serum concentration of Tiludronate can be increased when it is combined with Indomethacin.Approved, Investigational
IndoprofenThe risk or severity of adverse effects can be increased when Indoprofen is combined with Tiludronate.Withdrawn
INNO-206INNO-206 may increase the hypocalcemic activities of Tiludronate.Investigational
Iron saccharateThe serum concentration of Tiludronate can be decreased when it is combined with Iron saccharate.Approved
IsoxicamThe risk or severity of adverse effects can be increased when Isoxicam is combined with Tiludronate.Withdrawn
KanamycinKanamycin may increase the hypocalcemic activities of Tiludronate.Approved, Vet Approved
KebuzoneThe risk or severity of adverse effects can be increased when Kebuzone is combined with Tiludronate.Experimental
KetoprofenThe risk or severity of adverse effects can be increased when Ketoprofen is combined with Tiludronate.Approved, Vet Approved
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Tiludronate.Approved
LansoprazoleThe therapeutic efficacy of Tiludronate can be decreased when used in combination with Lansoprazole.Approved, Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tiludronate.Approved, Investigational
LisofyllineThe risk or severity of adverse effects can be increased when Lisofylline is combined with Tiludronate.Investigational
LornoxicamThe risk or severity of adverse effects can be increased when Lornoxicam is combined with Tiludronate.Approved
LoxoprofenThe risk or severity of adverse effects can be increased when Loxoprofen is combined with Tiludronate.Approved
LumiracoxibThe risk or severity of adverse effects can be increased when Lumiracoxib is combined with Tiludronate.Approved, Investigational
Magnesium carbonateThe serum concentration of Tiludronate can be decreased when it is combined with Magnesium carbonate.Approved
Magnesium hydroxideThe serum concentration of Tiludronate can be decreased when it is combined with Magnesium hydroxide.Approved
Magnesium oxideThe serum concentration of Tiludronate can be decreased when it is combined with Magnesium oxide.Approved
Magnesium salicylateThe serum concentration of Tiludronate can be decreased when it is combined with Magnesium salicylate.Approved
Magnesium SulfateThe serum concentration of Tiludronate can be decreased when it is combined with Magnesium Sulfate.Approved, Vet Approved
Magnesium TrisilicateThe serum concentration of Tiludronate can be decreased when it is combined with Magnesium Trisilicate.Approved
MasoprocolThe risk or severity of adverse effects can be increased when Masoprocol is combined with Tiludronate.Approved
Meclofenamic acidThe risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Tiludronate.Approved, Vet Approved
Mefenamic acidThe risk or severity of adverse effects can be increased when Mefenamic acid is combined with Tiludronate.Approved
MeloxicamThe risk or severity of adverse effects can be increased when Meloxicam is combined with Tiludronate.Approved, Vet Approved
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Tiludronate.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Tiludronate.Withdrawn
MetrizamideMetrizamide may increase the hypocalcemic activities of Tiludronate.Approved
MizoribineThe risk or severity of adverse effects can be increased when Mizoribine is combined with Tiludronate.Investigational
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Tiludronate.Approved, Investigational
Mycophenolic acidThe risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Tiludronate.Approved
NabumetoneThe risk or severity of adverse effects can be increased when Nabumetone is combined with Tiludronate.Approved
NafamostatThe risk or severity of adverse effects can be increased when Nafamostat is combined with Tiludronate.Investigational
NaftifineThe risk or severity of adverse effects can be increased when Naftifine is combined with Tiludronate.Approved
NaproxenThe risk or severity of adverse effects can be increased when Naproxen is combined with Tiludronate.Approved, Vet Approved
NCX 4016The risk or severity of adverse effects can be increased when NCX 4016 is combined with Tiludronate.Investigational
NeamineNeamine may increase the hypocalcemic activities of Tiludronate.Experimental
NeomycinNeomycin may increase the hypocalcemic activities of Tiludronate.Approved, Vet Approved
NepafenacThe risk or severity of adverse effects can be increased when Nepafenac is combined with Tiludronate.Approved
NetilmicinNetilmicin may increase the hypocalcemic activities of Tiludronate.Approved
Niflumic AcidThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with Tiludronate.Approved
NimesulideThe risk or severity of adverse effects can be increased when Nimesulide is combined with Tiludronate.Approved, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Nitroaspirin is combined with Tiludronate.Investigational
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Tiludronate.Approved
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Tiludronate.Approved
OmeprazoleThe therapeutic efficacy of Tiludronate can be decreased when used in combination with Omeprazole.Approved, Investigational, Vet Approved
OrgoteinThe risk or severity of adverse effects can be increased when Orgotein is combined with Tiludronate.Vet Approved
OxaprozinThe risk or severity of adverse effects can be increased when Oxaprozin is combined with Tiludronate.Approved
OxyphenbutazoneThe risk or severity of adverse effects can be increased when Oxyphenbutazone is combined with Tiludronate.Withdrawn
PantoprazoleThe therapeutic efficacy of Tiludronate can be decreased when used in combination with Pantoprazole.Approved
ParecoxibThe risk or severity of adverse effects can be increased when Parecoxib is combined with Tiludronate.Approved
ParomomycinParomomycin may increase the hypocalcemic activities of Tiludronate.Approved, Investigational
PhenylbutazoneThe risk or severity of adverse effects can be increased when Phenylbutazone is combined with Tiludronate.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Tiludronate.Approved, Investigational
PirarubicinPirarubicin may increase the hypocalcemic activities of Tiludronate.Investigational
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Tiludronate.Investigational
PiroxicamThe risk or severity of adverse effects can be increased when Piroxicam is combined with Tiludronate.Approved, Investigational
PlicamycinPlicamycin may increase the hypocalcemic activities of Tiludronate.Approved, Withdrawn
PropacetamolThe risk or severity of adverse effects can be increased when Propacetamol is combined with Tiludronate.Approved
PTC299The risk or severity of adverse effects can be increased when PTC299 is combined with Tiludronate.Investigational
PuromycinPuromycin may increase the hypocalcemic activities of Tiludronate.Experimental
RabeprazoleThe therapeutic efficacy of Tiludronate can be decreased when used in combination with Rabeprazole.Approved, Investigational
ResveratrolThe risk or severity of adverse effects can be increased when Resveratrol is combined with Tiludronate.Experimental, Investigational
RibostamycinRibostamycin may increase the hypocalcemic activities of Tiludronate.Approved
RofecoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tiludronate.Investigational, Withdrawn
SalicylamideThe risk or severity of adverse effects can be increased when Salicylamide is combined with Tiludronate.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Tiludronate.Approved, Vet Approved
SalsalateThe risk or severity of adverse effects can be increased when Salsalate is combined with Tiludronate.Approved
SeratrodastThe risk or severity of adverse effects can be increased when Seratrodast is combined with Tiludronate.Approved, Investigational
SisomicinSisomicin may increase the hypocalcemic activities of Tiludronate.Investigational
SP1049CSP1049C may increase the hypocalcemic activities of Tiludronate.Investigational
SpectinomycinSpectinomycin may increase the hypocalcemic activities of Tiludronate.Approved, Vet Approved
SRT501The risk or severity of adverse effects can be increased when SRT501 is combined with Tiludronate.Investigational
StreptomycinStreptomycin may increase the hypocalcemic activities of Tiludronate.Approved, Vet Approved
StreptozocinStreptozocin may increase the hypocalcemic activities of Tiludronate.Approved
SulfasalazineThe risk or severity of adverse effects can be increased when Sulfasalazine is combined with Tiludronate.Approved
SulindacThe risk or severity of adverse effects can be increased when Sulindac is combined with Tiludronate.Approved
SuprofenThe risk or severity of adverse effects can be increased when Suprofen is combined with Tiludronate.Approved, Withdrawn
TAK-390MRThe therapeutic efficacy of Tiludronate can be decreased when used in combination with TAK-390MR.Investigational
TenoxicamThe risk or severity of adverse effects can be increased when Tenoxicam is combined with Tiludronate.Approved
TepoxalinThe risk or severity of adverse effects can be increased when Tepoxalin is combined with Tiludronate.Vet Approved
TeriflunomideThe risk or severity of adverse effects can be increased when Teriflunomide is combined with Tiludronate.Approved
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Tiludronate.Approved
TinoridineThe risk or severity of adverse effects can be increased when Tinoridine is combined with Tiludronate.Investigational
TobramycinTobramycin may increase the hypocalcemic activities of Tiludronate.Approved, Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Tolfenamic Acid is combined with Tiludronate.Approved
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Tiludronate.Approved
TranilastThe risk or severity of adverse effects can be increased when Tranilast is combined with Tiludronate.Approved, Investigational
Trisalicylate-cholineThe risk or severity of adverse effects can be increased when Trisalicylate-choline is combined with Tiludronate.Approved
ValdecoxibThe risk or severity of adverse effects can be increased when Valdecoxib is combined with Tiludronate.Investigational, Withdrawn
ValrubicinValrubicin may increase the hypocalcemic activities of Tiludronate.Approved
ZaltoprofenThe risk or severity of adverse effects can be increased when Zaltoprofen is combined with Tiludronate.Approved
ZileutonThe risk or severity of adverse effects can be increased when Zileuton is combined with Tiludronate.Approved, Investigational, Withdrawn
ZomepiracThe risk or severity of adverse effects can be increased when Zomepirac is combined with Tiludronate.Withdrawn
ZorubicinZorubicin may increase the hypocalcemic activities of Tiludronate.Experimental
Food Interactions
  • Do not take aluminum or magnesium-containing antacids within 2 hours of taking tiludronate.
  • Take on an empty stomach (at least 2 hours before or after meals) with a full glass of plain water. Other beverages may reduce drug absorption.
References
Synthesis Reference

William Rocco, Sharon M. Laughlin, “Stable pharmaceutical compositions containing tiludronate hydrates and process for producing the pharmaceutical compositions.” U.S. Patent US5656288, issued April, 1995.

US5656288
General References
  1. Murakami H, Takahashi N, Sasaki T, Udagawa N, Tanaka S, Nakamura I, Zhang D, Barbier A, Suda T: A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone. 1995 Aug;17(2):137-44. [PubMed:8554921 ]
  2. Rogers MJ: New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des. 2003;9(32):2643-58. [PubMed:14529538 ]
  3. Sansom LN, Necciari J, Thiercelin JF: Human pharmacokinetics of tiludronate. Bone. 1995 Nov;17(5 Suppl):479S-483S. [PubMed:8573422 ]
External Links
ATC CodesM05BA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8821
Blood Brain Barrier+0.92
Caco-2 permeable-0.69
P-glycoprotein substrateNon-substrate0.82
P-glycoprotein inhibitor INon-inhibitor0.9497
P-glycoprotein inhibitor IINon-inhibitor0.9907
Renal organic cation transporterNon-inhibitor0.9293
CYP450 2C9 substrateNon-substrate0.7291
CYP450 2D6 substrateNon-substrate0.8201
CYP450 3A4 substrateNon-substrate0.7084
CYP450 1A2 substrateNon-inhibitor0.7348
CYP450 2C9 inhibitorNon-inhibitor0.7404
CYP450 2D6 inhibitorNon-inhibitor0.8875
CYP450 2C19 inhibitorNon-inhibitor0.7287
CYP450 3A4 inhibitorNon-inhibitor0.8637
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.871
Ames testNon AMES toxic0.8148
CarcinogenicityCarcinogens 0.509
BiodegradationNot ready biodegradable0.9882
Rat acute toxicity2.9059 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.939
hERG inhibition (predictor II)Non-inhibitor0.9362
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Skelid 200 mg tablet11.47USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1327009 No1994-02-152011-02-15Canada
US4876248 No1993-01-302010-01-30Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP-0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.97 mg/mLALOGPS
logP0.62ALOGPS
logP1.32ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)1.03ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area115.06 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity65.11 m3·mol-1ChemAxon
Polarizability25.37 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
KingdomOrganic compounds
Super ClassOrganophosphorus compounds
ClassOrganic phosphonic acids and derivatives
Sub ClassBisphosphonates
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • Thiophenol ether
  • Alkylarylthioether
  • Halobenzene
  • Chlorobenzene
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Organophosphonic acid
  • Sulfenyl compound
  • Thioether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organochloride
  • Organohalogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
antagonist
References
  1. Jahnke W, Henry C: An in vitro assay to measure targeted drug delivery to bone mineral. ChemMedChem. 2010 May 3;5(5):770-6. doi: 10.1002/cmdc.201000016. [PubMed:20209564 ]
  2. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. [PubMed:16046206 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Proton-transporting atpase activity, rotational mechanism
Specific Function:
Catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
Gene Name:
ATP6V1A
Uniprot ID:
P38606
Molecular Weight:
68303.5 Da
References
  1. David P, Nguyen H, Barbier A, Baron R: The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase. J Bone Miner Res. 1996 Oct;11(10):1498-507. [PubMed:8889850 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Zinc ion binding
Specific Function:
Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repu...
Gene Name:
PTPN1
Uniprot ID:
P18031
Molecular Weight:
49966.44 Da
References
  1. Murakami H, Takahashi N, Tanaka S, Nakamura I, Udagawa N, Nakajo S, Nakaya K, Abe M, Yuda Y, Konno F, Barbier A, Suda T: Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts. Bone. 1997 May;20(5):399-404. [PubMed:9145236 ]
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Drug created on June 13, 2005 07:24 / Updated on December 08, 2016 11:11